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Ahmed S, Elahi T, Mubarak M, Ahmed E. Clinicopathological characteristics and long-term outcomes of adult patients with proliferative lupus nephritis. World J Nephrol 2025; 14:102713. [DOI: 10.5527/wjn.v14.i2.102713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 02/25/2025] [Accepted: 03/04/2025] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND Proliferative lupus nephritis (PLN) is the most severe form of lupus nephritis (LN). There are limited data available on renal outcomes of PLN from developing countries.
AIM To determine the clinicopathological characteristics and long-term outcomes in terms of remission, requirement of kidney replacement therapy (KRT), and patient survival.
METHODS A retrospective analysis was conducted on biopsy-proven focal or diffuse PLN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation and followed up at the renal clinic for a minimum of 5 years. All patients were induced with a combination of intravenous cyclophosphamide and corticosteroids for 6 months, followed by maintenance treatment with azathioprine (AZA) or mycophenolate mofetil (MMF). Data were analyzed using Statistical Package for the Social Sciences, version 22.0. P ≤ 0.05 was considered statistically significant.
RESULTS The mean age at the onset of systemic lupus erythematosus was 24.12 years ± 8.89 years, and at LN onset, 26.63 years ± 8.61 years. There was a female predominance of 184 (88.9%) cases. Among baseline characteristics, reduced estimated glomerular filtration rate, presence of hypertension, requirement of KRT, and underlying renal histology (International Society of Nephrology/Renal Pathology Society class IV than class III) were significantly associated with end-stage kidney disease (ESKD) and mortality. The renal outcomes were negatively correlated with age, duration of symptoms, and 24-hour urinary protein excretion. The overall remission rate was 89.8% at the end of induction therapy. At 5 years, 141 (68.11%) patients were in complete and partial remission (94 [45.4%] and 47 [22.7%], respectively). In total, 19 (9.2%) patients required KRT on presentation, and at 5 years, 38 (18.4%) patients developed ESKD, and 28 (13.5%) patients died. Thirty-four (16.4%) patients had a renal relapse, more with AZA than MMF (30 [88.2%] vs 4 [11.76%], respectively; P = 0.04). Renal survival at 6 months was 89.8%, while at 5 years, it was 68.11%, showing a significant improvement in patients who did not need KRT at the time of presentation (P < 0.0001).
CONCLUSION Baseline renal functions, requirement of KRT, and diffuse proliferative disease were the most relevant prognostic factors for kidney survival among this cohort. Short-term renal outcomes were good. Long-term outcomes were poorer with AZA-based maintenance therapy than with MMF, with more ESKD and mortality.
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Affiliation(s)
- Saima Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Tabassum Elahi
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Ejaz Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
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Loganathan G, Palanivelan M. An explainable adaptive channel weighting-based deep convolutional neural network for classifying renal disorders in computed tomography images. Comput Biol Med 2025; 192:110220. [PMID: 40315718 DOI: 10.1016/j.compbiomed.2025.110220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 03/19/2025] [Accepted: 04/12/2025] [Indexed: 05/04/2025]
Abstract
Renal disorders are a significant public health concern and a cause of mortality related to renal failure. Manual diagnosis is subjective, labor-intensive, and depends on the expertise of nephrologists in renal anatomy. To improve workflow efficiency and enhance diagnosis accuracy, we propose an automated deep learning model, called EACWNet, which incorporates adaptive channel weighting-based deep convolutional neural network and explainable artificial intelligence. The proposed model categorizes renal computed tomography images into various classes, such as cyst, normal, tumor, and stone. The adaptive channel weighting module utilizes both global and local contextual insights to refine the final feature map channel weights through the integration of a scale-adaptive channel attention module in the higher convolutional blocks of the VGG-19 backbone model employed in the proposed method. The efficacy of the EACWNet model has been assessed using a publicly available renal CT images dataset, attaining an accuracy of 98.87% and demonstrating a 1.75% improvement over the backbone model. However, this model exhibits class-wise precision variation, achieving higher precision for cyst, normal, and tumor cases but lower precision for the stone class due to its inherent variability and heterogeneity. Furthermore, the model predictions have been subjected to additional analysis using the explainable artificial intelligence method such as local interpretable model-agnostic explanations, to visualize better and understand the model predictions.
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Affiliation(s)
- G Loganathan
- Department of Electronics and Communication Engineering, Rajalakshmi Engineering College, Chennai 602105, India.
| | - M Palanivelan
- Department of Electronics and Communication Engineering, Rajalakshmi Engineering College, Chennai 602105, India.
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Liu T, Hu M, Bai Y, Zhang J, Deng Y, Shen L, Zhou L. Correlations of the Complement Proteins MASP-2 and MASP-3 With Clinical Severity and Short-Term Outcomes in Primary Membranous Nephropathy Patients. Nephrology (Carlton) 2025; 30:e70041. [PMID: 40294883 DOI: 10.1111/nep.70041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 11/03/2024] [Accepted: 04/16/2025] [Indexed: 04/30/2025]
Abstract
AIM This study aimed to explore the serum levels of mannose binding lectin-associated serine protease 2(MASP-2) and 3(MASP-3) in primary membranous nephropathy (PMN) patients and its correlation with clinical activity and short-term prognosis. METHODS Serum levels of MASP-2, MASP-3 and C5a were measured in 72 PMN patients, 71 IgAN patients and 30 healthy controls via enzyme-linked immunosorbent assay (ELISA). Correlations between complement activation biomarkers and clinical parameters were analysed using Spearman correlation. Logistic regression analysis was used to identify risk factors for short-term clinical non-remission in PMN patients, and the predictive performance of the factors was evaluated using ROC curves and the area under the ROC curve (AUC). RESULTS Serum MASP-2 levels in the PMN group were lower than in both the healthy control and IgAN groups, while levels in the IgAN group were higher than in the healthy control group. Serum levels of MASP-3 and C5a in the PMN group were not significantly different from those in the IgAN group. Both patient groups had significantly elevated serum levels of MASP-3 and C5a compared to the healthy control group. In PMN patients, serum MASP-3 and C5a levels correlated with clinical indicators such as eGFR, serum creatinine and 24-h urinary protein. Multivariate logistic regression analysis revealed that serum anti-phospholipase A2 receptor antibody (anti-PLA2R-ab) and MASP-3 were independent risk factors for the non-remission of PMN at 12 months. The combined detection of serum MASP-3 and anti-PLA2R-ab had a greater AUC for predicting early non-remission than either factor alone. CONCLUSION Serum MASP-3 and C5a can serve as biomarkers reflecting the clinical severity of PMN. The combined detection of serum MASP-3 and anti-PLA2R-ab will improve the prediction efficiency of PMN prognosis.
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Affiliation(s)
- Tong Liu
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
| | - Miao Hu
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
| | - Yujie Bai
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
| | - Jiayan Zhang
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
| | - Yi Deng
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
| | - Lei Shen
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
| | - Ling Zhou
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China
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Zanoni F, Marasa M, Carlassara L, Verbitsky M, Khan A, Wang C, Bundy JD, Canetta PA, Bomback AS, Parsa A, Feldman HI, Gharavi AG, Kiryluk K. Family History in the Context of CKD. J Am Soc Nephrol 2025:00001751-990000000-00583. [PMID: 40067412 DOI: 10.1681/asn.0000000653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Abstract
Background A family history of health conditions may reflect shared genetic and/or environmental risk. It is not well known to what extent family history affects outcomes among patients with CKD. In this study, we investigated the associations of family history of CKD, diabetes, and other conditions with common comorbidities and kidney disease progression among patients with CKD. Methods We performed an observational study of two prospective CKD cohorts, 2573 adults and children from the Cure Glomerulopathy Network and 3939 Chronic Renal Insufficiency Cohort adult participants. Self-reported first-degree family history of CKD, diabetes, and other common diseases was tested for associations with the risk of comorbidities and CKD progression using multivariable models. Results Family history of common comorbid conditions was associated with higher risk of these conditions in the context of CKD, including approximately by over three-fold for diabetes (adjusted odds ratio [OR], 3.37; 95% confidence interval [CI], 2.73 to 4.15), 48% for cancer (adjusted OR, 1.48; 95% CI, 1.05 to 2.09), and 69% for cardiovascular disease (adjusted OR, 1.69; 95% CI, 1.36 to 2.10 in combined cohorts). While polygenic risk score (PRS) for CKD was associated with kidney disease progression (adjusted hazards ratio, 1.11; 95% CI, 1.06 to 1.16 in combined cohorts), family history of kidney disease was not an independent risk factor of disease progression in the context of existing CKD. By contrast, family history of diabetes was significantly associated with a higher risk of CKD progression independently of diabetes occurrence or PRS for diabetes (adjusted hazards ratio, 1.19; 95% CI, 1.05 to 1.35 in combined cohorts). Conclusions Broad collection of family history in the context of CKD improved clinical risk stratification. Family history of diabetes was consistently associated with a higher risk of CKD progression independently of diabetes status or PRS for diabetes in both cohorts.
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Affiliation(s)
- Francesca Zanoni
- Department of Nephrology, Dialysis, and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Maddalena Marasa
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Lucrezia Carlassara
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Miguel Verbitsky
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Atlas Khan
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Chen Wang
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Joshua D Bundy
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana
| | - Pietro A Canetta
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Andrew S Bomback
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Afshin Parsa
- Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
| | - Harold I Feldman
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ali G Gharavi
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
- Center for Precision Medicine and Genomics, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Krzysztof Kiryluk
- Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
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Meena P, Panda S, Das P, Garg A, Purkait S, Ayyanar P. Short Communication: Analysis of the Spectrum of Glomerular Diseases in Chronic Filariasis Diagnosed in a Tertiary Care Hospital in India. Vector Borne Zoonotic Dis 2025; 25:220-222. [PMID: 39607722 DOI: 10.1089/vbz.2024.0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024] Open
Abstract
Introduction: The study presents renal manifestations in chronic filariasis, a substantial health concern in the eastern and north-eastern regions of India. Materials and Methods: The study is a retrospective analysis of a renal biopsy series of patients with chronic filariasis from a tertiary care hospital in Odisha. It involves eight cases of chronic filariasis. Results: Common indications of biopsy were nephrotic syndrome, chyluria, and unexplained renal failure. The mean duration from the diagnosis of filariasis to the onset of glomerular diseases was 15.75 years, SD ± 4.2 years. Patients were followed up for a minimum of 6 months. Renal histopathology revealed various patterns, including membranous nephropathy, minimal change disease, IGA nephropathy, and membranoproliferative glomerulonephritis. Conclusion: The study fills a critical gap in the literature by elucidating renal biopsy findings in chronic filariasis. The multifaceted nature of this disease underscores the need for continued research to understand kidney diseases due to filariasis, especially in endemic regions.
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Affiliation(s)
- Priti Meena
- Department of Nephrology, All India Institute of Medical Sciences-Bhubaneswar, Bhubaneswar, Odisha, India
| | - Sandip Panda
- Department of Nephrology, All India Institute of Medical Sciences-Bhubaneswar, Bhubaneswar, Odisha, India
| | - Paromita Das
- Department of Nephrology, All India Institute of Medical Sciences-Bhubaneswar, Bhubaneswar, Odisha, India
| | - Anish Garg
- Department of Nephrology, All India Institute of Medical Sciences-Bhubaneswar, Bhubaneswar, Odisha, India
| | - Suvendu Purkait
- Department of Pathology, All India Institute of Medical Sciences-Bhubaneswar, Bhubaneswar, Odisha, India
| | - Pavithra Ayyanar
- Department of Pathology, All India Institute of Medical Sciences-Bhubaneswar, Bhubaneswar, Odisha, India
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Zhang H, Ren S, Hu J, Li G. Long-term renal survival in patients with IgA nephropathy: a systematic review. Ren Fail 2024; 46:2394636. [PMID: 39192601 PMCID: PMC11360644 DOI: 10.1080/0886022x.2024.2394636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 08/13/2024] [Accepted: 08/15/2024] [Indexed: 08/29/2024] Open
Abstract
The management strategy for IgA nephropathy (IgAN), has undergone constant improvements since the disease entity was first described 50 years ago. However, it is still unknown how these changes affected the long-term renal survival of IgAN patients. We systematically evaluate changes in IgAN renal survival by searching PubMed, Embase, and the Cochrane Library Database of Systematic Reviews from inception to 19 May 2024. We included a large sample of 103076 IgAN cases from 158 studies. Renal survival rates were 94.16% (95% CI: 94.02% to 94.31%), 88.68% (95% CI: 88.48% to 88.87%), and 78.13% (95% CI: 77.82% to 78.43%) at three, five, and ten-year, respectively. Over the past few decades, there haven't been any sound changes in the 3-year and 5-year renal survival rates. The kidney survival rate in developed countries is higher than in developing countries. Researchers consistently show that while proteinuria < 1.0 g/24 h, renal survival rates increase dramatically. In IgAN, long-term renal survival fluctuated rather than continuously improving over time. Our system review's findings indicate that supportive care-the most important recommendation for managing IgAN has shown promising results. The long-term outcomes of IgAN could be significantly improved by the latest developed treatment options.
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Affiliation(s)
- Huijian Zhang
- Renal Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Song Ren
- Renal Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jieqiang Hu
- Renal Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Guisen Li
- Renal Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
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Wang WR, Yang YZ, Xing Y, Zhou ZA, Jiang QY, Huang LY, Kong LD, Zhang DM. The trans-differentiation promotion of parietal epithelial cells by magnesium isoglycyrrhizinate to improve podocyte injury induced by high fructose consumption. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156242. [PMID: 39566408 DOI: 10.1016/j.phymed.2024.156242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 10/22/2024] [Accepted: 11/07/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND Podocytes have limited proliferative capacity, which leads to irreversible glomerular injury in diverse kidney diseases. Magnesium isoglycyrrhizinate (MgIG), a hepatoprotective agent in clinic, has been reported to improve glomerular podocyte injury. However, the underlying mechanism of MgIG in ameliorating podocyte injury remains unclear. PURPOSE Glomerular parietal epithelial cells (PECs) are recognized as podocyte progenitors and play a pivotal role in the recovery following glomerular injury. This work aims to investigate the protective mechanisms of MgIG in mitigating glomerular injury by promoting PEC trans-differentiation. STUDY DESIGN A rat model of progressive glomerular podocyte injury, and in vitro models using the primary podocytes and primary PECs, were established to further explore the pharmacological mechanism of MgIG. METHODS Four-week-old male Sprague-Dawley (SD) rats were fed a 10 % fructose solution for 3, 6, 9 and 12 weeks to induce glomerular injury. The effects of MgIG on the progressive changes in podocytes and PECs, and the correlation between PEC density and podocyte loss, were analyzed. The mechanism of MgIG in triggering PEC trans-differentiation was investigated, by examining adenosine secretion in injured podocytes, as well as the expression of cluster of differentiation 44 (CD44), nephrin, adenosine receptor A2B (ARA2B) and glucocorticoid receptor (GR) in PECs both in vivo and in vitro. RESULTS Rats fed a high fructose diet exhibited progressive changes in glomerular PECs, including increased cell density and a preference for trans-differentiation. A positive correlation was observed between PEC density and podocyte loss. Co-culture experiments demonstrated that extracellular adenosine accumulation from injured podocytes induced by high fructose exposure promoted PEC trans-differentiation via ARA2B. MgIG significantly improved podocyte injury and exhibited effects similar to dexamethasone on nephrin upregulation and CD44 inhibition. Moreover, the effect of MgIG on PEC ARA2B activation was more effective than that of dexamethasone. The co-expression of paired box 2 (PAX2)+-Nephrin+ in glomeruli indicated that MgIG induced PEC trans-differentiation and podocyte regeneration in model rats. Accordingly, podocyte loss and increased urine albumin-to-creatinine ratio (UACR) were also alleviated. Moreover, MgIG, which acts as a GR agonist to activate GR, reversed the upregulation of CD44 and decreased ARA2B induced by tumor necrosis factor-α (TNF-α) in primary PECs. The siRNA interference experiment manifested that MgIG exhibited a more pronounced enhancement of GR upregulation, in contrast to ARA2B activation, to promote PEC trans-differentiation. CONCLUSION This work reports for the first time that PECs respond to the accumulation of extracellular adenosine from injured podocytes via activating ARA2B and focuses on the role of adenosine and adenosine receptors in the trans-differentiation of PECs. Furthermore, this study provides the first evidence that MgIG may promote podocyte regeneration by enhancing PEC trans-differentiation through GR activation, providing a research basis for investigating the glucocorticoid-like activity of MgIG in ameliorating glomerular podocyte injury.
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Affiliation(s)
- Wan-Ru Wang
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Ying-Zhi Yang
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Yu Xing
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Zi-Ang Zhou
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Qiao-Yun Jiang
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Lu-Yi Huang
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Ling-Dong Kong
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China
| | - Dong-Mei Zhang
- School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China.
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Zhu Y, Chen B, Xu G. Efficacy and safety of nine immunosuppressive agents for primary focal segmental glomerulosclerosis in adults: a pairwise and network meta-analysis. Ren Fail 2024; 46:2438861. [PMID: 39663153 PMCID: PMC11636141 DOI: 10.1080/0886022x.2024.2438861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 11/30/2024] [Accepted: 12/02/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Immunosuppressants are widely used as the preferred treatment for primary focal segmental glomerulosclerosis (pFSGS). Nevertheless, controversies persist regarding the effectiveness and side effects of different immunosuppressive medications. METHODS From July 2023 until June 2024, we systematically searched PubMed, Cochrane Library, Web of Science, clinicalrials.gov, SinoMed, Chinese Biomedical, Chinese National Knowledge Infrastructure, Wanfang, and VIP information. Randomized controlled trials comparing different immunosuppressants were included in adult patients with pFSGS, with total remission (TR) and 24-h urine total protein (24-h UTP) as the main outcome measures. RESULTS We identified 20 RCTs comparing nine different immunosuppressants for the final analysis. Most immunosuppressants showed better therapeutic effects in TR compared to non-immunosuppressive therapies (NIT), with risk ratios (RRs) of 2.22 (95% CI 1.41-3.50) for cyclosporin, 2.10 (1.57-2.80) for leflunomide-combined steroids, 2.01 (1.24-3.27) for chlorambucil-combined steroids, 1.98 (1.17-3.33) for tacrolimus-combined steroids, 1.89 (1.36-2.63) for cyclosporin-combined steroids, 1.67 (1.28-2.18) for mycophenolate mofetil-combined steroids, and 1.47 (1.21-1.80) for steroids. Only mycophenolate mofetil-combined steroids (SMD -11, 95% CI -21 to -0.64) showed significant superiority in reducing 24-h UTP when compared with NIT. The subgroup analyses of steroids-resistant nephrotic syndrome (SRNS) patients showed that CSA + STE was significantly superior than the NIT group, with RR of 10.5 (95% CI 2.28-44.35). CONCLUSION Steroids remain the recommended initial treatment for pFSGS. For those patients with SRNS, CSA + STE might be the best choice for improving the rate of TR. LEF + STE and MMF + STE also appear to offer a steroid-saving alternative to high-dose glucocorticoids for patients.
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Affiliation(s)
- Yan Zhu
- Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China
| | - Bo Chen
- Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China
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Guo Y, Qiu Y, Xue T, Yan P, Zhao W, Wang M, Liu C, Zhang N. Association between admission baseline blood potassium levels and all-cause mortality in patients with acute kidney injury combined with sepsis: A retrospective cohort study. PLoS One 2024; 19:e0309764. [PMID: 39565797 PMCID: PMC11578480 DOI: 10.1371/journal.pone.0309764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 08/17/2024] [Indexed: 11/22/2024] Open
Abstract
INTRODUCTION Imbalances in blood potassium (K) homeostasis is a significant contributor to the emergence of severe complications, especially among critically ill patients. Hypokalemia and hyperkalemia are both associated with an increased risk of adverse events. However, it is not known about the impact of blood K levels on risk of intensive care units (ICU) mortality for Acute kidney injury (AKI) combined with sepsis patients. This study aimed to explore the relationship between admission blood K levels and ICU 30-day mortality in patients with AKI combined with sepsis. METHODS We selected patients diagnosed with AKI and sepsis on their first ICU admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The first blood K levels within 24 hours of admission were categorized into three groups according to tertiles (T1 < 3.9 mmol/L, 3.9 ≤ T2 < 4.5 mmol/L, and T3 ≥ 4.5 mmol/L), with T2 serving as the reference. We examined the association between blood K levels and ICU 30-day mortality using accelerated failure time (AFT) models and survival analysis. RESULTS A total of 8,242 ICU patients with AKI combined with sepsis were included. In multivariate AFT models, each 1 mmol/L increase in blood K levels was associated with a 13% increase in the risk of ICU 30-day mortality (p < 0.001, 95% confidence interval (CI): 1.06-1.20). Extended multivariable AFT models showed that, compared to the middle category, patients with high blood K levels (≥ 4.5 mmol/L) were associated with all-cause mortality (p = 0.002, adjusted hazard ratio (HR) = 1.22, 95% CI: 1.08-1.38), whereas those with low blood K levels (< 3.9 mmol/L) showed no significant difference (p = 0.385, adjusted HR = 1.06, 95% CI: 0.93-1.21). Kaplan-Meier curves indicated that patients with high blood K levels had higher mortality, and those with middle blood potassium levels (3.9 ≤ K < 4.5 mmol/L) had the lowest mortality. CONCLUSION The admission baseline blood K levels were significantly associated with ICU 30-day mortality in intensive care patients suffering from AKI in conjunction with sepsis. Therefore, immediate and careful correction of blood potassium imbalances may prove to be a crucial approach in improving outcomes for these patients.
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Affiliation(s)
- Yifan Guo
- Department of Endocrinology and Nephropathy, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yue Qiu
- Department of Endocrinology, Miyun Hospital District, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Taiqi Xue
- Department of Endocrinology and Nephropathy, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Pu Yan
- Department of Endocrinology and Nephropathy, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenjing Zhao
- Department of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Mengdi Wang
- Department of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Cheng Liu
- Department of Human Anatomy, Program for Cancer and Cell Biology, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Ning Zhang
- Department of Endocrinology and Nephropathy, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
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Chen L, Chen X, Cai G, Jiang H, Chen X, Zhang M. An inflammatory cytokine signature predicts IgA nephropathy severity and progression. MedComm (Beijing) 2024; 5:e783. [PMID: 39492831 PMCID: PMC11531656 DOI: 10.1002/mco2.783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 11/05/2024] Open
Abstract
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, resulting in end-stage renal disease and increased mortality rates. Prognostic biomarkers reflecting molecular mechanisms for effective IgAN management are urgently needed. Analysis of kidney single-cell transcriptomic sequencing data demonstrated that IgAN expressed high-expression levels of inflammatory cytokines TNFSF10, TNFSF12, CCL2, CXCL1, and CXCL12 than healthy controls (HCs). We also measured the urine proteins in 120 IgAN (57 stable and 63 progressive) and 32 HCs using the proximity extension assay (PEA), and the multivariable and least absolute shrinkage and selection operator (LASSO) logistic regression analysis both revealed that CXCL12, MCP1 were the prognostic significant variables to predict IgAN progression severity. These two proteins exhibited negative correlation with the estimated glomerular filtration rate (eGFR) and patients with higher expression levels of these two proteins had a higher probability to have poorer renal outcome. We further developed a risk index model utilizing CXCL12, MCP1, and baseline clinical indicators, which achieved an impressive area under the curve (AUC) of 0.896 for prediction of IgAN progression severity. Our study highlights the significance of the inflammatory protein biomarkers for noninvasive prediction of IgAN severity and progression, offering valuable insights for clinical management.
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Affiliation(s)
- Lei Chen
- Department of Critical Care Nephrology and Blood Purificationthe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Xizhao Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijingChina
| | - Guangyan Cai
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijingChina
| | - Hongli Jiang
- Department of Critical Care Nephrology and Blood Purificationthe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijingChina
| | - Min Zhang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijingChina
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11
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Pillebout E. IgA Vasculitis and IgA Nephropathy: Two Sides of the Same Coin? Semin Nephrol 2024; 44:151571. [PMID: 40069065 DOI: 10.1016/j.semnephrol.2025.151571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2025]
Abstract
IgA vasculitis (IgAV) is considered a systemic form of IgA nephropathy (IgAN). The two diseases share similar geographic and ethnic distribution, along with common variants in genetic association studies. The pathophysiology of IgAN and IgA vasculitis nephritis (IgAVN) can be explained by the four-hit hypothesis. Key molecules involved at each step in both diseases were evaluated as diagnostic and prognostic biomarkers with many common factors, most prominently serum galactose-deficient IgA1. On kidney biopsy, the two diseases are indistinguishable, and the established histological Oxford classification for IgAN will soon be validated for IgAVN. Chronic lesions (segmental glomerulosclerosis and tubular atrophy / interstitial fibrosis) seem more frequent in IgAN, while proliferative lesions (endocapillary hypercellularity and crescents) are more frequent in IgAVN, which could explain the worse IgAN renal prognosis. Due to characteristic skin rash, IgAVN patients are diagnosed precociously. Conversely, the frequent absence of overt clinical signs in IgAN leads to a delayed diagnostic kidney biopsy in the disease evolution, which explains the chronic pathologic lesions. From a therapeutic perspective, while impressive advances have been made in recent years for IgAN, there is a glaring lack of evidence-based guidelines for the treatment of IgAVN. Large therapeutic clinical studies are required, and future IgAN trials should include IgAVN.
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Affiliation(s)
- Evangéline Pillebout
- Nephrology and Renal Transplant Unit, St Louis Hospital, 1 Avenue Claude Vellefaux 75010, Paris, France.
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12
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Zhang D, Sun D. Current progress in CAR-based therapy for kidney disease. Front Immunol 2024; 15:1408718. [PMID: 39234257 PMCID: PMC11372788 DOI: 10.3389/fimmu.2024.1408718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 08/05/2024] [Indexed: 09/06/2024] Open
Abstract
Despite significant breakthroughs in the understanding of immunological and pathophysiological features for immune-mediated kidney diseases, a proportion of patients exhibit poor responses to current therapies or have been categorized as refractory renal disease. Engineered T cells have emerged as a focal point of interest as a potential treatment strategy for kidney diseases. By genetically modifying T cells and arming them with chimeric antigen receptors (CARs), effectively targeting autoreactive immune cells, such as B cells or antibody-secreting plasma cells, has become feasible. The emergence of CAR T-cell therapy has shown promising potential in directing effector and regulatory T cells (Tregs) to the site of autoimmunity, paving the way for effective migration, proliferation, and execution of suppressive functions. Genetically modified T-cells equipped with artificial receptors have become a novel approach for alleviating autoimmune manifestations and reducing autoinflammatory events in the context of kidney diseases. Here, we review the latest developments in basic, translational, and clinical studies of CAR-based therapies for immune-mediated kidney diseases, highlighting their potential as promising avenues for therapeutic intervention.
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Affiliation(s)
- Dan Zhang
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Dong Sun
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China
- Clinical Research Center For Kidney Disease, Xuzhou Medical University, Xuzhou, China
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13
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Kimachi M, Ikenoue T, Fukuma S. Prevalent and new use of common drugs for the incidence of community-acquired acute kidney injury: cohort and case-crossover study. Sci Rep 2024; 14:17906. [PMID: 39095424 PMCID: PMC11297046 DOI: 10.1038/s41598-024-66532-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 07/02/2024] [Indexed: 08/04/2024] Open
Abstract
Although community-acquired acute kidney injury (CA-AKI) represents a significant subset of all AKI incidence, evidence is limited due to the lack of comprehensive data prior to diagnosis. Here, we examined the risk of drug use for CA-AKI by using exhaustive pre-diagnostic prescription data. We included 78,754 working-age healthy individuals who underwent an annual health checkup program. We conducted a cohort study to assess the association between prevalent drug use and subsequent CA-AKI incidence using the Cox proportional hazard model. Subsequently, we conducted a case-crossover study to compare the new drug use in the case period directly before the CA-AKI incidence (- 3 to 0 months) with that in the control period far before the CA-AKI incidence (- 15 to - 12 months and - 9 to - 6 months) using the conditional Poisson regression model. The prevalent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with an increased CA-AKI incidence, but the new use was not. The new use of diuretics, anti-infectious drugs, and contrast medium was also associated with an increased CA-AKI incidence. These results suggest we need to pay attention for the incidence of AKI among the general population taking those common drugs.
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Affiliation(s)
- Miho Kimachi
- Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin-Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Tatsuyoshi Ikenoue
- Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin-Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
- Shiga University Center for Data Science Education and Research, Shiga, Japan
| | - Shingo Fukuma
- Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin-Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
- Department of Epidemiology Infectious Disease Control and Prevention, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
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Bi X, Yu Y, Zhou S, Zhou Y, Zhao J, Xiong J. Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1. Nephron Clin Pract 2024; 148:587-600. [PMID: 38723614 DOI: 10.1159/000534788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 10/11/2023] [Indexed: 06/19/2024] Open
Abstract
INTRODUCTION The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research. METHODS A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS + immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. RESULTS 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS + immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-h proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 mL/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. CONCLUSION Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.
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Affiliation(s)
- Xianjin Bi
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Department of Cardiovasology, People's Liberation Army Joint Logistic Support Force 945th Hospital, Yaan, China
| | - Yanlin Yu
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Siyan Zhou
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yue Zhou
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jinghong Zhao
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jiachuan Xiong
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
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15
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Barratt J, Liew A, Yeo SC, Fernström A, Barbour SJ, Sperati CJ, Villanueva R, Wu MJ, Wang D, Borodovsky A, Badri P, Yureneva E, Bhan I, Cattran D. Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial. Clin J Am Soc Nephrol 2024; 19:452-462. [PMID: 38214599 PMCID: PMC11020434 DOI: 10.2215/cjn.0000000000000384] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 12/15/2023] [Indexed: 01/13/2024]
Abstract
BACKGROUND IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. METHODS In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. RESULTS Thirty-one patients were randomized (cemdisiran, N =22; placebo, N =9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). CONCLUSIONS These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.
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Affiliation(s)
- Jonathan Barratt
- Department of Cardiovascular Medicine, University of Leicester, Leicester, United Kingdom
| | - Adrian Liew
- Mount Elizabeth Novena Hospital, Singapore, Singapore
| | - See Cheng Yeo
- Renal Medicine, Tan Tock Seng Hospital, Singapore, Singapore
| | - Anders Fernström
- Department of Nephrology, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Sean J. Barbour
- University of British Columbia, Division of Nephrology, Vancouver, British Columbia, Canada
| | - C. John Sperati
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Ming-Ju Wu
- Department of Internal Medicine, Taichung Veterans General Hospital and Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Dazhe Wang
- Alnylam Pharmaceuticals, Cambridge, Massachusetts
| | | | | | | | - Ishir Bhan
- Alnylam Pharmaceuticals, Cambridge, Massachusetts
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Li J, Dong Y, Chen F, Yang H, Chen P, Li H, Shi S, Zhou X, Zhu L, Zhang Y, Liu L, Xie X, Yu F, Jin J, Lv J, Zhang H. Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract. Front Immunol 2024; 15:1368322. [PMID: 38558821 PMCID: PMC10978756 DOI: 10.3389/fimmu.2024.1368322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 02/27/2024] [Indexed: 04/04/2024] Open
Abstract
Introduction Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.
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Affiliation(s)
- Jingyi Li
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Yaping Dong
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Feifei Chen
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Hongyu Yang
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Pei Chen
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Hongyu Li
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Sufang Shi
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Xujie Zhou
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Li Zhu
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Yuemiao Zhang
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Lijun Liu
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Xinfang Xie
- Department of Nephrology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
| | - Feng Yu
- Department of Nephrology, Peking University International Hospital, Beijing, China
| | - Jing Jin
- Northwestern University Feinberg School of Medicine, Division of Nephrology, Chicago, IL, United States
| | - Jicheng Lv
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Hong Zhang
- Renal Division, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
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Wei X, Long M, Fan Z, Hou Y, Zhu X, Qu Z, Du Y. Prediction of immunotherapy response in idiopathic membranous nephropathy using deep learning-pathological and clinical factors. Front Endocrinol (Lausanne) 2024; 15:1328579. [PMID: 38524629 PMCID: PMC10958378 DOI: 10.3389/fendo.2024.1328579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 02/26/2024] [Indexed: 03/26/2024] Open
Abstract
Background Owing to individual heterogeneity, patients with idiopathic membranous nephropathy (IMN) exhibit varying sensitivities to immunotherapy. This study aimed to establish and validate a model incorporating pathological and clinical features using deep learning training to evaluate the response of patients with IMN to immunosuppressive therapy. Methods The 291 patients were randomly categorized into training (n = 219) and validation (n = 72) cohorts. Patch-level convolutional neural network training in a weakly supervised manner was utilized to analyze whole-slide histopathological features. We developed a machine-learning model to assess the predictive value of pathological signatures compared to clinical factors. The performance levels of the models were evaluated using the area under the receiver operating characteristic curve (AUC) on the training and validation tests, and the prediction accuracies of the models for immunotherapy response were compared. Results Multivariate analysis indicated that diabetes and smoking were independent risk factors affecting the response to immunotherapy in IMN patients. The model integrating pathologic features had a favorable predictive value for determining the response to immunotherapy in IMN patients, with AUCs of 0.85 and 0.77 when employed in the training and test cohorts, respectively. However, when incorporating clinical features into the model, the predictive efficacy diminishes, as evidenced by lower AUC values of 0.75 and 0.62 on the training and testing cohorts, respectively. Conclusions The model incorporating pathological signatures demonstrated a superior predictive ability for determining the response to immunosuppressive therapy in IMN patients compared to the integration of clinical factors.
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Affiliation(s)
| | | | | | | | | | - Zhihui Qu
- *Correspondence: Zhihui Qu, ; Yujun Du,
| | - Yujun Du
- *Correspondence: Zhihui Qu, ; Yujun Du,
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Di Leo V, Annese F, Papadia F, Russo MS, Giliberti M, Sallustio F, Gesualdo L. Refractory IgA Nephropathy: A Challenge for Future Nephrologists. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:274. [PMID: 38399561 PMCID: PMC10890070 DOI: 10.3390/medicina60020274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/25/2024]
Abstract
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
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de Araújo EMC, Campos MAG, Sodré AM, de Holanda MI, Hagemann R, Teixeira Júnior AAL, Salgado Filho N, Neves PDMDM, Silva GEB. Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review. Vaccines (Basel) 2024; 12:62. [PMID: 38250875 PMCID: PMC10821173 DOI: 10.3390/vaccines12010062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/23/2024] Open
Abstract
Large-scale COVID-19 vaccination has been one of the most effective strategies to control the spread of the SARS-CoV-2 virus. However, several cases of glomerular injury related to the COVID-19 vaccine have been described in the literature. We report two cases of a tip lesion variant of focal segmental glomerulosclerosis (FSGS), which presented with significant proteinuria and improved after immunosuppression. In our literature review, the tip lesion variant of FSGS is currently the most frequent variant associated with vaccination against COVID-19. Prognosis is favorable and without significant alterations in the tubulointerstitial or vascular compartments. Adverse effects of vaccines need to be recognized early and will help us to understand the immune and pathological mechanisms of kidney damage.
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Affiliation(s)
- Emmy Marjorie Carvalho de Araújo
- Faculty of Medicine, Federal University of Maranhão, Gonçalves Dias Square, São Luís 65020-240, Brazil; (E.M.C.d.A.); (A.M.S.); (N.S.F.)
| | - Marcos Adriano Garcia Campos
- Clinical Hospital of Botucatu Medical School, São Paulo State University, Professor Mário Rubens Guimarães Montenegro Avenue, Botucatu 18618-687, Brazil;
| | - Andressa Monteiro Sodré
- Faculty of Medicine, Federal University of Maranhão, Gonçalves Dias Square, São Luís 65020-240, Brazil; (E.M.C.d.A.); (A.M.S.); (N.S.F.)
| | | | - Rodrigo Hagemann
- Clinical Hospital Complex, Federal University of Paraná, General Carneiro Street, Curitiba 80060-900, Brazil;
| | | | - Natalino Salgado Filho
- Faculty of Medicine, Federal University of Maranhão, Gonçalves Dias Square, São Luís 65020-240, Brazil; (E.M.C.d.A.); (A.M.S.); (N.S.F.)
| | | | - Gyl Eanes Barros Silva
- Faculty of Medicine, Federal University of Maranhão, Gonçalves Dias Square, São Luís 65020-240, Brazil; (E.M.C.d.A.); (A.M.S.); (N.S.F.)
- Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Avenue, Ribeirão Preto 14040-900, Brazil
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20
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Liu W, Su ZH, Wan QJ. Proteinuria selectivity index in renal disease. Clin Chim Acta 2024; 552:117675. [PMID: 38007057 DOI: 10.1016/j.cca.2023.117675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 11/16/2023] [Accepted: 11/20/2023] [Indexed: 11/27/2023]
Abstract
One of the main barriers to early detection and subsequent prevention of kidney diseases is the accessibility and feasibility of testing, especially in urine research. The proteinuria selectivity index (PSI or SI) is a method used to assess changes in glomerular permeability in glomerular diseases. It describes the pattern of proteinuria by comparing the clearance rates of large molecular proteins and transferrin, categorizing it as selective or non-selective. PSI is widely applied for kidney disease classification, prediction of corticosteroid efficacy, and prognosis. Herein, we reviewed the clinical applications and recent advancements of PSI in glomerular diseases, compared it with commonly used renal function biomarkers, and discussed the future research directions for PSI as a potential predictive marker for response to specific biologics.
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Affiliation(s)
- Wen Liu
- Department of Nephrology, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen 518036, China
| | - Zhi-Hang Su
- Department of Nephrology, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen 518036, China
| | - Qi-Jun Wan
- Department of Nephrology, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital), Shenzhen 518036, China.
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21
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Yeo SC, Barratt J. The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy. Clin Kidney J 2023; 16:ii9-ii18. [PMID: 38053976 PMCID: PMC10695512 DOI: 10.1093/ckj/sfad200] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Indexed: 12/07/2023] Open
Abstract
Advances in our understanding of the pathogenesis of immunoglobulin A nephropathy (IgAN) have led to the identification of novel therapeutic targets and potential disease-specific treatments. Specifically, a proliferation-inducing ligand (APRIL) has been implicated in the pathogenesis of IgAN, mediating B-cell dysregulation and overproduction of pathogenic galactose-deficient IgA1 (Gd-IgA1). Animal and clinical studies support the involvement of APRIL in the pathogenesis and progression of IgAN. An elevated level of APRIL is found in IgAN when compared with controls, which correlates with the level of Gd-IgA1 and associates with more severe disease presentation and worse outcomes. Conversely, anti-APRIL therapy reduces pathogenic Gd-IgA1 and IgA immune complex formation and ameliorates the severity of kidney inflammation and injury. Genome-wide association studies in IgAN have identified TNFSF13 and TNFRSF13B, a cytokine ligand-receptor gene pair encoding APRIL and its receptor, respectively, as risk susceptibility loci in IgAN, further supporting the causal role of the APRIL signalling pathway in IgAN. Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart and sibeprenlimab, are currently under investigation as potential therapies in IgAN. Preliminary results suggest that these agents are well-tolerated, and reduce levels of Gd-IgA1, with corresponding improvement in proteinuria. Further studies are ongoing to confirm the safety and efficacy of anti-APRIL approaches as an effective therapeutic strategy in IgAN.
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Affiliation(s)
- See Cheng Yeo
- Department of Renal Medicine, Tan Tock Seng Hospital, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Jonathan Barratt
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- John Walls Renal Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
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22
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Kang Y, Xu B, Shi S, Zhou X, Chen P, Liu L, Li Y, Leng Y, Lv J, Zhu L, Zhang H. Mesangial C3 Deposition, Complement-Associated Variant, and Disease Progression in IgA Nephropathy. Clin J Am Soc Nephrol 2023; 18:1583-1591. [PMID: 37651123 PMCID: PMC10723908 DOI: 10.2215/cjn.0000000000000290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 08/25/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND IgA nephropathy is the most common primary GN worldwide, with dominant deposition of IgA and co-deposits of complement component 3 (C3). Phenotypes and progression of IgA nephropathy varies among different ethnic populations, while patients with IgA nephropathy from Asia showed more severe clinical phenotypes, active kidney lesions, and rapid progression. Our previous genome-wide association study identified complement factor H ( CFH ) variant rs6677604, tightly linked with the deletion of CFH -related protein 3 and CFH -related protein 1 genes ( ΔCFHR3-1 ), as IgA nephropathy susceptible variant, and additionally revealed its effect on complement regulation in IgA nephropathy. METHODS To further explore the effect of rs6677604 on IgA nephropathy progression, here we enrolled a Chinese IgA nephropathy cohort of 1781 patients with regular follow-up for analysis. The rs6677604 genotype was measured, and the genotype-phenotype correlation was analyzed using the t test, the chi-squared test, or the nonparametric test, and the association between rs6677604 genotype or mesangial C3 deposition and IgA nephropathy prognosis was analyzed using Kaplan-Meier analysis and Cox regression. RESULTS We found that patients with rs6677604-GG genotype had a stronger intensity of mesangial C3 deposition than those with the rs6677604-AA/AG genotype. Patients with IgA nephropathy who had stronger intensity of C3 deposition manifested with more severe clinical and pathological manifestations, including lower eGFR and higher Oxford-M/S/T/C (mesangial hypercellularity, endocapillary cellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and crescent) scores. In the survival analysis, stronger intensity of mesangial C3 deposition, but not rs6677604-GG genotypes, was associated with poor long-term kidney outcome in IgA nephropathy. CONCLUSIONS We found that in Chinese patients with IgA nephropathy, variant rs6677604 was associated with mesangial C3 deposition, and mesangial C3 deposition, but not rs6677604, was associated with IgA nephropathy severity and progression.
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Affiliation(s)
- Yuqi Kang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease (Peking University), Beijing, China; National Health Commission, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China; and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
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23
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Deepthi RV, George S, Mathew G, Roy S, Bindra M, Rebekah G, Agarwal I. The Clinical Profile and Long-Term Outcome of Children with Membranous Nephropathy, and the Evaluation of Anti-Phospholipase A2 Receptor Antibody Immunohistochemistry in Kidney Biopsy. Indian J Nephrol 2023; 33:432-439. [PMID: 38174298 PMCID: PMC10752404 DOI: 10.4103/ijn.ijn_228_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 10/11/2022] [Accepted: 11/02/2022] [Indexed: 01/05/2024] Open
Abstract
Introduction Idiopathic membranous nephropathy (iMN) is a rare cause of nephrotic syndrome in children (1%-7%). Anti-phospholipase A2 receptor (PLA2R) antibody positivity in kidney biopsy is observed in 52%-78% of adults and 45% of children with iMN. The objectives of the study are to analyze the clinical profile and outcome of membranous nephropathy in children, to assess the prevalence of anti-PLA2R immunohistochemistry (IHC) in kidney biopsy, and to correlate their presence with disease characteristics. Methods We are reporting a single-center retrospective study conducted in pediatric nephrology division. Clinical data and outcome parameters of children with membranous nephropathy were analyzed. PLA2R IHC was performed in kidney biopsy specimens retrospectively. Results We analyzed 43 children with membranous nephropathy (MN) from a single center. 18 (42%) had idiopathic MN (iMN). PLA2R IHC was performed in kidney biopsy specimens in 14/18 (78%) patients with iMN and 7/9 (78%) non-lupus secondary membranous nephropathy (SMN) patients. The most common cause of SMN was lupus nephritis in 16 patients (64%). The mean estimated glomerular filtration rate (eGFR) at onset was 156 ± 81 ml/min/1.73m2. The sensitivity and specificity of PLA2R IHC in diagnosing pediatric MN was 50% and 57%, respectively; positive and negative predictive values were 70% and 36%, respectively. At the final follow-up, chronic kidney disease stage 5 (CKD 5) developed in 2/14 (14.3%) iMN patients. Conclusions IHC PLA2R staining of glomerular tissue is a useful diagnostic marker of IMN. Though PLA2R prevalence is lower in children, its role in guiding treatment needs further exploration.
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Affiliation(s)
- RV Deepthi
- Departments of Child Health, Division of Pediatric Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Sachin George
- Departments of Child Health, Division of Pediatric Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Georgie Mathew
- Departments of Child Health, Division of Pediatric Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Sanjeet Roy
- Department of General Pathology, Division of Renal Pathology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Mandeep Bindra
- Consultant in Pathology, Naruvi Hospital, Vellore, Tamil Nadu, India
| | - Grace Rebekah
- Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India
| | - Indira Agarwal
- Departments of Child Health, Division of Pediatric Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
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Baxter RM, Wang CS, Garcia-Perez JE, Kong DS, Coleman BM, Larchenko V, Schuyler RP, Jackson C, Ghosh T, Rudra P, Paul D, Claassen M, Rochford R, Cambier JC, Ghosh D, Cooper JC, Smith MJ, Hsieh EWY. Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus. Front Immunol 2023; 14:1208282. [PMID: 37965329 PMCID: PMC10641733 DOI: 10.3389/fimmu.2023.1208282] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 10/06/2023] [Indexed: 11/16/2023] Open
Abstract
Introduction Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown. Methods We analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI). Results cSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis. Discussion This study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.
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Affiliation(s)
- Ryan M. Baxter
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Christine S. Wang
- Department of Pediatrics, Section of Rheumatology, School of Medicine, University of Colorado, Children’s Hospital Colorado, Aurora, CO, United States
| | - Josselyn E. Garcia-Perez
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Daniel S. Kong
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Brianne M. Coleman
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Valentyna Larchenko
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Ronald P. Schuyler
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Conner Jackson
- Center for Innovative Design and Analysis, School of Public Health, University of Colorado, Aurora, CO, United States
| | - Tusharkanti Ghosh
- Department of Biostatistics and Informatics, School of Public Health, University of Colorado, Aurora, CO, United States
| | - Pratyaydipta Rudra
- Department of Statistics, Oklahoma State University, Stillwater, OK, United States
| | - Debdas Paul
- Clinical Bioinformatics & Machine Learning in Translational Single-Cell Biology, University of Tuebingen, Tuebingen, Germany
| | - Manfred Claassen
- Clinical Bioinformatics & Machine Learning in Translational Single-Cell Biology, University of Tuebingen, Tuebingen, Germany
| | - Rosemary Rochford
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - John C. Cambier
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Debashis Ghosh
- Department of Biostatistics and Informatics, School of Public Health, University of Colorado, Aurora, CO, United States
| | - Jennifer C. Cooper
- Department of Pediatrics, Section of Rheumatology, School of Medicine, University of Colorado, Children’s Hospital Colorado, Aurora, CO, United States
| | - Mia J. Smith
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
- Department of Pediatrics, Barbara Davis Center for Diabetes, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Elena W. Y. Hsieh
- Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO, United States
- Department of Pediatrics, Section of Allergy and Immunology, School of Medicine, University of Colorado, Children’s Hospital Colorado, Aurora, CO, United States
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Yu G, Jiang Y, Xu Z, Cheng J, Li H, Li X, Chen J. Plasma D-dimer as a potential predictor of progression in IgA nephropathy: a cohort study. Ren Fail 2023; 45:2251587. [PMID: 37724549 PMCID: PMC10512868 DOI: 10.1080/0886022x.2023.2251587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 08/20/2023] [Indexed: 09/21/2023] Open
Abstract
INTRODUCTION Coagulation disorders play a key role in chronic kidney disease, and the formation or elevation of plasma D-dimer levels reflects activation of the coagulation system. However, its relationship with the severity and progression of kidney disease in IgA nephropathy (IgAN) remains unclear. METHODS We assessed 1818 patients with IgAN diagnosed between 2002 and 2019 at the First Affiliated Hospital, Zhejiang University School of Medicine. Plasma D-dimer levels were measured at the time of the renal biopsy. The association between plasma D-dimer levels and kidney disease progression events, defined as a 50% decline in eGFR and end-stage kidney disease (ESKD), was tested using restricted cubic splines and Cox proportional hazard models. RESULTS The median plasma D-dimer level was 220 (170-388.5) µg/L FEU, which was significantly higher than healthy controls 170 (170-202) µg/L FEU. Plasma D-dimer levels were positively correlated with proteinuria (r = 0.211, p < 0.001) and serum galactose-deficient IgA1 (r = 0.226, p = 0.004) and negatively correlated with eGFR (r=-0.127, p < 0.001) and Oxford T (p < 0.001) and C (p = 0.004) scores. After a median follow-up of 25.67 (13.03-47.44) months, 126 (6.93%) patients experienced composite kidney disease progression events. Higher plasma D-dimer levels were associated with an increased risk of kidney disease progression events (hazard ratio, 1.73; 95% confidence interval [95% CI], 1.40-2.23) per ln-transformed plasma D-dimer (p < 0.001), after adjustment for sex, age, proteinuria, Mean arterial pressure (MAP) and Oxford classification scores. In reference to the first tertile of plasma D-dimer, hazard ratios were 1.48 (95% CI, 0.76-2.88) for the second tertile, 3.03 (95% CI, 1.58-5.82) for the third tertile. CONCLUSIONS High plasma D-dimer levels were associated with the progression of kidney disease severity in IgA nephropathy.
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Affiliation(s)
- Guizhen Yu
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou, China
| | - Yan Jiang
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou, China
| | - Zishu Xu
- Intensive Care Unit, The Third People’s Provincial Hospital of Henan Province, Zhengzhou, China
| | - Jun Cheng
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou, China
| | - Heng Li
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou, China
| | - Xiayu Li
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province; National Key Clinical Department of Kidney Diseases; Institute of Nephrology, Zhejiang University; the Third Grade Laboratory under the National State, Administration of Traditional Chinese Medicine, Hangzhou, China
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26
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Chabannes M, Rabant M, El Sissy C, Dragon-Durey MA, Vieira Martins P, Meuleman MS, Karras A, Buob D, Bridoux F, Daugas E, Audard V, Caillard S, Olagne J, Kandel C, Ferlicot S, Philipponnet C, Crepin T, Thervet E, Ducloux D, Frémeaux-Bacchi V, Chauvet S. C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features. Am J Kidney Dis 2023; 82:279-289. [PMID: 37061020 DOI: 10.1053/j.ajkd.2022.12.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 12/31/2022] [Indexed: 04/17/2023]
Abstract
RATIONALE & OBJECTIVE C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients. STUDY DESIGN Case series. SETTING & PARTICIPANTS Patients with C3GN and concomitant TMA lesions on biopsy registered from 2009 to 2019 in the French National Registry of C3GN. FINDINGS Among 278 registered patients with C3GN, 16 (6%) had biopsy-proven glomerular and/or vascular TMA lesions. Their median age at diagnosis was 39 years (range, 7-76), and 59% were female. Fourteen of the 16 patients (88%) had an estimated glomerular filtration rate of<30mL/min/1.73m2 and 3 of 16 (19%) required dialysis. Twelve of the 14 evaluated patients (86%) showed evidence of mechanical hemolysis. Fifty percent of the patients had low C3 levels. Six of the 14 evaluated patients had a rare variant in complement genes, and 4 of the 16 patients (25%) had monoclonal gammopathy. Among the 16 patients, 10 (63%) received eculizumab, 5 (31%) received immunosuppressive therapy, and 4 (25%) received clone-targeted chemotherapy. Median kidney survival was 49 months. LIMITATIONS Small retrospective case series with a limited number of biopsies including electron microscopy. CONCLUSIONS Concomitant C3GN and TMA is extremely rare and is associated with poor kidney outcomes. Genetic or acquired abnormalities of the alternative complement pathway are common as is the presence of monoclonal gammopathy, which may inform the selection of treatment approaches.
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Affiliation(s)
- Melchior Chabannes
- Department of Nephrology, Dialysis and Renal Transplantation, University Hospital, Besançon
| | - Marion Rabant
- Department of Pathology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris; Université de Paris Cité, Paris, France
| | - Carine El Sissy
- Department of Biological Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris
| | - Marie-Agnès Dragon-Durey
- Department of Biological Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris; INSERM UMRS 1138, Cordelier Research Center, Paris; Université de Paris Cité, Paris, France
| | - Paula Vieira Martins
- Department of Biological Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris
| | - Marie Sophie Meuleman
- INSERM UMRS 1138, Cordelier Research Center, Paris; Université de Paris Cité, Paris, France
| | - Alexandre Karras
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris
| | - David Buob
- Department of Pathology, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris
| | - Frank Bridoux
- Department of Nephrology, Dialysis and Renal Transplantation, University Hospital, Poitiers
| | - Eric Daugas
- Department of Nephrology, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris
| | - Vincent Audard
- Department of Nephrology and Transplantation, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Créteil; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France
| | - Sophie Caillard
- Department of Nephrology and Transplantation, University Hospital, Strasbourg
| | - Jérôme Olagne
- Department of Pathology, University Hospital, Strasbourg
| | | | - Sophie Ferlicot
- Department of Pathology, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre
| | | | - Thomas Crepin
- Department of Nephrology, Dialysis and Renal Transplantation, University Hospital, Besançon
| | - Eric Thervet
- INSERM UMRS 1138, Cordelier Research Center, Paris
| | - Didier Ducloux
- Department of Nephrology, Dialysis and Renal Transplantation, University Hospital, Besançon
| | - Véronique Frémeaux-Bacchi
- Department of Biological Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris
| | - Sophie Chauvet
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris; INSERM UMRS 1138, Cordelier Research Center, Paris; Université de Paris Cité, Paris, France.
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27
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Cybulsky AV, Cercena L, Goodyer PR, Suri RS. Transition From Pediatric to Adult Nephrology Care: Program Report of a Single-Center Experience. Can J Kidney Health Dis 2023; 10:20543581231191836. [PMID: 37564323 PMCID: PMC10411281 DOI: 10.1177/20543581231191836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 06/23/2023] [Indexed: 08/12/2023] Open
Abstract
Purpose of program Adolescents and young adults with chronic disease face many personal and systemic barriers that may impede their successful transition from pediatric to adult care, putting them at risk for treatment nonadherence, loss to follow-up, and poor health outcomes. Such barriers include impaired socioemotional functioning, overreliance on adult caregivers, lack of disease-specific knowledge, and poor coordination between pediatric and adult health care services. In 2007, we established a specialized youth to adult nephrology transition clinic at a tertiary care center to address these barriers and provide adolescents and young adults with renal disease followed at the affiliated children's hospital with a seamless transition to adult care. Sources of information The attending clinic nephrologist collected data prospectively for this quality improvement report. Methods The features of this specialized clinic included (1) single point of entry and single triage adult nephrologist, (2) ongoing follow-up with a single adult nephrologist who communicated with the pediatric nephrologists, and (3) a single specialized clinic nurse who provided disease-specific education and helped to ensure ongoing patient engagement and follow-up. Importantly, the transition patients were booked into regular appointment slots in the adult nephrologist's general clinic, which facilitated regular follow-up without additional resources. The salary of the transition clinic nurse was covered by an unrestricted grant. Patient visits were in-person, except between 2020 and 2021 when visits were by telephone due to the pandemic. Key findings A total of 213 patients were referred and assessed in the transition clinic from February 2007 until October 2022. Most referrals were from pediatric nephrologists. Among the patients, 29% had a hereditary kidney disease; in 71%, the disease was acquired. The most common disease was glomerulonephritis and ~30% of the patients suffered from a "rare" disease. Of the 213 patients, 123 (58%) continue to be followed up (mean follow-up: 4.8 years), 27 (13%) were transferred to other physicians, in part to accommodate treatment closer to patients' homes, and 29 (14%) without ongoing care needs were discharged. Only 33 (15%) were lost to follow-up. There were several advantages to the clinic, including the maintenance of accurate records, a process to minimize loss to follow-up, and a "critical mass" of patients with rare diseases, which facilitated development of special expertise in rare disease pathogenesis, diagnosis, treatment, and management of complications. Patients with glomerulonephritis demonstrated a stable serum creatinine over 3 to 15 years, and morbidity (as reflected by emergency room visits and hospitalizations) was low. Limitations Due to the relatively small numbers of patients in the disease categories, it was not possible to determine conclusively whether attendance of patients in the transition clinic reduced the rate of progression of kidney disease or morbidity. Implications A dedicated referral, triage, and follow-up process post-transition with only modest financial resources and personnel can result in accurate tracking of clinic data, as well as consistent and reliable follow-up and expert patient care.
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Affiliation(s)
- Andrey V. Cybulsky
- Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, QC, Canada
| | - Leonor Cercena
- Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, QC, Canada
| | - Paul R. Goodyer
- Department of Pediatrics, McGill University Health Centre Research Institute, McGill University, Montreal, QC, Canada
| | - Rita S. Suri
- Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, QC, Canada
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Zheng X, Liu D, Zhu J, Lu L, Yang J. Age- and Gender-Specific Diagnostic Value of the Albumin-to-Creatinine Ratio for the Early Screening of Chronic Kidney Disease Among Middle-Aged and Elderly Males in Southeast China. Int J Gen Med 2023; 16:3033-3042. [PMID: 37465553 PMCID: PMC10351596 DOI: 10.2147/ijgm.s419100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 07/05/2023] [Indexed: 07/20/2023] Open
Abstract
Objective To evaluate the potential diagnostic value of the albumin-to-creatinine ratio (ACR) in screening for early kidney injury in a physically examined population from Southeast China. Methods A total of 13,250 candidates were selected. Urinary ACR values <30, 30-300, and >300 mg/g were utilized as positive cut-off points to denote normal proteinuria, microalbuminuria, and macroalbuminuria, respectively. Results Age, systolic blood pressure, diastolic blood pressure, body mass index, waistline, fasting blood glucose, glycated hemoglobin, triglycerides, and high-density lipoprotein cholesterol were significantly different among the three groups. eGFR was negatively correlated with the levels of sCr, BUN, and UA in the microalbuminuria and macroalbuminuria groups. Furthermore, there was a significant difference in CKD stage between the normal and abnormal urine ACR groups. Meanwhile, for the 20-40 years patients, the eGFR, sCr and BUN showed no significant difference between microalbuminuria group compared with the normal proteinuria group; in contrast, for the 41-60 years and >61 years patients, eGFR, sCr, BUN and UA were all markedly increase in microalbuminuria and macroalbuminuria group in comparison with the normal proteinuria group. Finally, for the 41-60 males, only eGFR significantly decreased in microalbuminuria group compared with the normal proteinuria group, while for the 41-60 females, only UA showed no significant difference between microalbuminuria group and normal proteinuria group. On the other hand, for the >61 males, eGFR, sCr and BUN all significantly changed between microalbuminuria group and normal proteinuria group, while for the >61 females, eGFR, sCr and BUN all showed no significant difference between microalbuminuria group and normal proteinuria group, as well as microalbuminuria group and macroalbuminuria group. Conclusion We proposed using the urinary ACR for the screening of physically examined patients, especially among the elderly males. This approach would assist in the early diagnosis and treatment of renal damage.
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Affiliation(s)
- Xiang Zheng
- Department of Health Management Center, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Dan Liu
- Department of Health Management Center, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Jing Zhu
- Department of Health Management Center, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Li Lu
- Department of Health Management Center, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Jianshu Yang
- Department of Health Management Center, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
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Hua MR, Zhao YL, Yang JZ, Zou L, Zhao YY, Li X. Membranous nephropathy: Mechanistic insights and therapeutic perspectives. Int Immunopharmacol 2023; 120:110317. [PMID: 37207447 DOI: 10.1016/j.intimp.2023.110317] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 04/13/2023] [Accepted: 05/08/2023] [Indexed: 05/21/2023]
Abstract
Membranous nephropathy (MN) is one of the most common causes of non-diabetic nephrotic syndrome in adults. About 80% of cases are renal limited (primary MN) and 20% are associated with other systemic diseases or exposures (secondary MN). Autoimmune reaction is the main pathogenic factor of MN, and the discovery of autoantigens including the phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A has led to new insights into the pathogenesis, they can induce humoral immune responses led by IgG4 makes them suitable for the diagnosis and monitoring of MN. In addition, complement activation, genetic susceptibility genes and environmental pollution are also involved in MN immune response. In clinical practice, due to the spontaneous remission of MN, the combination of supportive therapy and pharmacological treatment is widely used. Immunosuppressive drugs are the cornerstone of MN treatment, and the dangers and benefits of this approach vary from person to person. In summary, this review provides a more comprehensive review of the immune pathogenesis, interventions and unresolved issues of MN in the hope of providing some new ideas for clinical and scientific researchers in the treatment of MN.
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Affiliation(s)
- Meng-Ru Hua
- Xi'an International Medical Center Hospital, Northwest University, No. 777 Xitai Road, Xi'an, Shaanxi 710000, China
| | - Yan-Long Zhao
- Xi'an International Medical Center Hospital, Northwest University, No. 777 Xitai Road, Xi'an, Shaanxi 710000, China
| | - Jun-Zheng Yang
- Guangdong nephrotic drug Engineering Technology Research Center, Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, No. 71 Dongpeng avenue, Guangzhou, Guangdong 510530, China
| | - Liang Zou
- School of Food and Bioengineering, Chengdu University, No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106, China
| | - Ying-Yong Zhao
- Xi'an International Medical Center Hospital, Northwest University, No. 777 Xitai Road, Xi'an, Shaanxi 710000, China; School of Food and Bioengineering, Chengdu University, No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106, China; School of Pharmacy, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, Zhejiang 310053, China.
| | - Xia Li
- Xi'an International Medical Center Hospital, Northwest University, No. 777 Xitai Road, Xi'an, Shaanxi 710000, China.
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Ghaddar M, Barratt J, Barbour SJ. An update on corticosteroid treatment for IgA nephropathy. Curr Opin Nephrol Hypertens 2023; 32:263-270. [PMID: 36866805 DOI: 10.1097/mnh.0000000000000881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023]
Abstract
PURPOSE OF REVIEW The use of corticosteroids to treat IgA nephropathy (IgAN) has been limited by many controversies related to uncertain benefit and safety concerns. Recent trials have tried to address these limitations. RECENT FINDINGS After being paused because of an excess of adverse events in the full-dose steroid arm, the TESTING trial compared a reduced dose of methylprednisolone to placebo in patients with IgAN after optimization of supportive therapy. Steroid treatment was associated with a significant reduction in the risk of a 40% decline in estimated glomerular filtration rate (eGFR), kidney failure and kidney death as well as a sustained decrease in proteinuria compared with placebo. Serious adverse events were more frequent with the full dose regimen but less common in the reduced dose regimen. A phase III trial evaluating a new formulation of targeted-release budesonide showed a significant reduction in short-term proteinuria and has resulted in accelerated FDA approval for use in the United States. In a subgroup analysis of DAPA-CKD trial, sodium-glucose transport protein 2 inhibitors reduced the risk of kidney function decline in patients who have completed or are not eligible for immunosuppression. SUMMARY Both reduced-dose corticosteroids and targeted-release budesonide are new therapeutic options that can be used in patients with high-risk disease. More novel-targeted therapies with a better safety profile are currently under investigations.
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Affiliation(s)
- Malak Ghaddar
- Division of Nephrology, University of British Columbia
- BC Renal, Vancouver, British Columbia, Canada
| | - Jonathan Barratt
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Sean J Barbour
- Division of Nephrology, University of British Columbia
- BC Renal, Vancouver, British Columbia, Canada
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Flores-Chova A, Martinez-Arroyo O, Riffo-Campos AL, Ortega A, Forner MJ, Cortes R. Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis. Int J Mol Sci 2023; 24:ijms24087088. [PMID: 37108249 PMCID: PMC10139178 DOI: 10.3390/ijms24087088] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/31/2023] [Accepted: 04/05/2023] [Indexed: 04/29/2023] Open
Abstract
Despite considerable progress in our understanding of systemic lupus erythematosus (SLE) pathophysiology, patient diagnosis is often deficient and late, and this has an impact on disease progression. The aim of this study was to analyze non-coding RNA (ncRNA) packaged into exosomes by next-generation sequencing to assess the molecular profile associated with renal damage, one of the most serious complications of SLE, to identify new potential targets to improve disease diagnosis and management using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The plasma exosomes had a specific ncRNA profile associated with lupus nephritis (LN). The three ncRNA types with the highest number of differentially expressed transcripts were microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and piwi-interacting RNAs (piRNAs). We identified an exosomal 29-ncRNA molecular signature, of which 15 were associated only with LN presence; piRNAs were the most representative, followed by lncRNAs and miRNAs. The transcriptional regulatory network showed a significant role for four lncRNAs (LINC01015, LINC01986, AC087257.1 and AC022596.1) and two miRNAs (miR-16-5p and miR-101-3p) in network organization, targeting critical pathways implicated in inflammation, fibrosis, epithelial-mesenchymal transition and actin cytoskeleton. From these, a handful of potential targets, such as transforming growth factor-β (TGF-β) superfamily binding proteins (activin-A, TGFB receptors, etc.), WNT/β-catenin and fibroblast growth factors (FGFs) have been identified for use as therapeutic targets of renal damage in SLE.
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Affiliation(s)
- Ana Flores-Chova
- Cardiometabolic and Renal Risk Research Group, INCLIVA Biomedical Research Institute, 46010 Valencia, Spain
| | - Olga Martinez-Arroyo
- Cardiometabolic and Renal Risk Research Group, INCLIVA Biomedical Research Institute, 46010 Valencia, Spain
| | - Angela L Riffo-Campos
- Millennium Nucleus on Sociomedicine (SocioMed) and Universidad de La Frontera, Doctorado en Ciencias Medicas, Temuco 4780000, Chile
- Department of Computer Science, ETSE, University of Valencia, 46010 Valencia, Spain
| | - Ana Ortega
- Cardiometabolic and Renal Risk Research Group, INCLIVA Biomedical Research Institute, 46010 Valencia, Spain
- CIBERCV (CIBER of Cardiovascular Diseases), 28029 Madrid, Spain
| | - Maria J Forner
- Internal Medicine Unit, Hospital Clinico Universitario, 46010 Valencia, Spain
- Department of Medicine, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
| | - Raquel Cortes
- Cardiometabolic and Renal Risk Research Group, INCLIVA Biomedical Research Institute, 46010 Valencia, Spain
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Ge XY, Lan ZK, Lan QQ, Lin HS, Wang GD, Chen J. Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease. Eur Radiol 2023; 33:2386-2398. [PMID: 36454259 PMCID: PMC10017610 DOI: 10.1007/s00330-022-09268-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 08/15/2022] [Accepted: 10/24/2022] [Indexed: 12/02/2022]
Abstract
OBJECTIVES To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. METHODS The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. RESULTS A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). CONCLUSION A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. KEY POINTS • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.
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Affiliation(s)
- Xin-Yue Ge
- Department of Medical Ultrasound, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China
| | - Zhong-Kai Lan
- Department of Medical Ultrasound, Liuzhou People's Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, China
| | - Qiao-Qing Lan
- Department of Radiology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Hua-Shan Lin
- Department of Pharmaceutical Diagnosis, GE Healthcare, Changsha, 410005, China
| | - Guo-Dong Wang
- Department of Oncology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China.
| | - Jing Chen
- Department of Medical Ultrasound, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China.
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Trautmann A, Boyer O, Hodson E, Bagga A, Gipson DS, Samuel S, Wetzels J, Alhasan K, Banerjee S, Bhimma R, Bonilla-Felix M, Cano F, Christian M, Hahn D, Kang HG, Nakanishi K, Safouh H, Trachtman H, Xu H, Cook W, Vivarelli M, Haffner D. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2023; 38:877-919. [PMID: 36269406 PMCID: PMC9589698 DOI: 10.1007/s00467-022-05739-3] [Citation(s) in RCA: 97] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/03/2022] [Accepted: 08/22/2022] [Indexed: 01/19/2023]
Abstract
Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.
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Affiliation(s)
- Agnes Trautmann
- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
| | - Olivia Boyer
- Department of Pediatric Nephrology, Reference Center for Idiopathic Nephrotic Syndrome in Children and Adults, Imagine Institute, Paris University, Necker Children's Hospital, APHP, Paris, France
| | - Elisabeth Hodson
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia
| | - Arvind Bagga
- Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Debbie S Gipson
- Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
| | - Susan Samuel
- Section of Pediatric Nephrology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada
| | - Jack Wetzels
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Khalid Alhasan
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Sushmita Banerjee
- Department of Pediatric Nephrology, Institute of Child Health, Kolkata, India
| | | | - Melvin Bonilla-Felix
- Department of Pediatrics, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico
| | - Francisco Cano
- Department of Pediatric Nephrology, Luis Calvo Mackenna Children's Hospital, University of Chile, Santiago, Chile
| | - Martin Christian
- Children's Kidney Unit, Nottingham Children's Hospital, Nottingham, UK
| | - Deirdre Hahn
- Division of Pediatric Nephrology, Department of Paediatrics, The Children's Hospital at Westmead, Sydney, Australia
| | - Hee Gyung Kang
- Division of Pediatric Nephrology, Department of Pediatrics, Seoul National University Children's Hospital & Seoul National University College of Medicine, Seoul, Korea
| | - Koichi Nakanishi
- Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Hesham Safouh
- Pediatric Nephrology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Howard Trachtman
- Department of Pediatrics, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA
| | - Hong Xu
- Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China
| | - Wendy Cook
- Nephrotic Syndrome Trust (NeST), Somerset, UK
| | - Marina Vivarelli
- Division of Nephrology and Dialysis, Department of Pediatric Subspecialties, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy
| | - Dieter Haffner
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover and Center for Rare Diseases, Hannover Medical School, Hannover, Germany.
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Ekrikpo U, Obiagwu P, Chika-Onu U, Yadla M, Karam S, Tannor EK, Bello AK, Okpechi IG. Epidemiology and Outcomes of Glomerular Diseases in Low- and Middle-Income Countries. Semin Nephrol 2023; 42:151316. [PMID: 36773418 DOI: 10.1016/j.semnephrol.2023.151316] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Glomerular diseases account for a significant proportion of chronic kidney disease in low-income and middle-income countries (LMICs). The epidemiology of glomerulonephritis is characterized inadequately in LMICs, largely owing to unavailable nephropathology services or uncertainty of the safety of the kidney biopsy procedure. In contrast to high-income countries where IgA nephropathy is the dominant primary glomerular disease, focal segmental glomerulosclerosis is common in large populations across Latin America, Africa, Middle East, and South East Asia, while IgA nephropathy is common in Chinese populations. Despite having a high prevalence of known genetic and viral risk factors that trigger focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis also is common in adults and children in some African countries. Treatment of glomerular diseases in adults and children in LMICs largely is dependent on corticosteroids in combination with other immunosuppressive therapy, which often is cyclophosphamide because of its ready availability and low cost of treatment, despite significant adverse effects. Partial and/or complete remission status reported from studies of glomerular disease subtypes vary across LMIC regions, with high rates of kidney failure, mortality, and disease, and treatment complications often reported. Improving the availability of nephropathology services and ensuring availability of specific therapies are key measures to improving glomerular disease outcomes in LMICs.
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Affiliation(s)
- Udeme Ekrikpo
- Department of Medicine, University of Uyo, Uyo, Nigeria
| | - Patience Obiagwu
- Department of Paediatrics, Bayero University, Aminu Kano Teaching Hospital, Kano, Nigeria
| | - Ugochi Chika-Onu
- Department of Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla, Enugu, Nigeria
| | - Manjusha Yadla
- Department of Nephrology, Gandhi Medical College, Hyderabad, Telangana, India
| | - Sabine Karam
- Division of Nephrology, University of Minnesota, Minnesota, MN; Division of Nephrology, Faculty of Medicine and Medical Sciences, University of Balamand, Balamand, Lebanon
| | - Elliot K Tannor
- Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Aminu K Bello
- Department of Medicine, University of Alberta, Edmonton, Canada
| | - Ikechi G Okpechi
- Department of Medicine, University of Alberta, Edmonton, Canada; Division of Nephrology, University of Cape Town, Cape Town, South Africa.
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Zhang J, Fan Z, Wang P, Zhang AH. Phospholipase A2 Receptor Antibodies and Clinical Prognosis in Patients with Idiopathic Membranous Nephropathy: An Updated Systematic Review and Meta-Analysis. Kidney Blood Press Res 2023; 48:102-113. [PMID: 36720217 DOI: 10.1159/000529415] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/23/2023] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. OBJECTIVE Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. METHOD PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. RESULTS Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (-) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (-) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. CONCLUSION In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.
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Affiliation(s)
- Jialing Zhang
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China,
| | - Zhengjia Fan
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Peixin Wang
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Ai-Hua Zhang
- Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing, China
- The National Clinical Research Center for Geriatric Disease, Xuanwu Hospital, Capital Medical University, Beijing, China
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Chen P, Mao M, Wang C, Zhang X, Zhao X, Gao Y, Luo Y, Zhou Y. Preliminary study on the efficacy of rituximab in the treatment of idiopathic membranous nephropathy: A single-centre experience. Front Endocrinol (Lausanne) 2023; 14:1044782. [PMID: 36875477 PMCID: PMC9974647 DOI: 10.3389/fendo.2023.1044782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/02/2023] [Indexed: 02/17/2023] Open
Abstract
OBJECTIVE To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy (IMN). METHODS A total of 77 patients with IMN diagnosed in both our hospital and other hospitals were included in this study; the patients were divided into two groups: a treatment-naïve group (n = 19) and a refractory/relapsed group (n = 58). The clinical data of the patients, including urine examination, blood test, safety evaluation and efficacy evaluation results, were analysed retrospectively. The changes in clinical biochemical indexes and adverse reactions were compared between the two groups before and after treatment, and the clinical efficacy of rituximab (RTX) in the treatment of primary IMN and refractory recurrent membranous nephropathy was evaluated. RESULTS Of the 77 patients included in this study, the average age was 48 years, and there was a male-to-female ratio of 61:16. There were 19 cases in the initial treatment group and 58 cases in the refractory/relapse group. The 24-hour urine protein quantification, cholesterol, B cell count and M-type phospholipase A2 receptor (PLA2R) results in the 77 patients with IMN after treatment were all lower than those before treatment, and the differences were statistically significant (P < 0.05). Serum albumin was higher than before treatment, and the difference was statistically significant (P < 0.05). The total remission rate in the initial and refractory/relapsed treatment groups was 84.21% and 82.76%, respectively. There was no statistical difference in the total remission rate between the two groups (P > 0.05). During treatment, nine patients (11.69%) experienced infusion-related adverse reactions, which were relieved rapidly after symptomatic treatment. The anti-PLA2R antibody titre of the refractory/relapsed group was significantly negatively correlated with serum creatinine (r = -0.187, P = 0.045) and significantly correlated with 24-hour urine protein (r = -0.490, P < 0.001). There was a positive correlation and a significant negative correlation with serum albumin (r = -0.558, P < 0.001). CONCLUSIONS Regardless of whether RTX is used as an initial therapy or refractory/relapsed membranous nephropathy, most patients with IMN have complete or partial remission after RTX treatment, with mild adverse reactions.
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Affiliation(s)
- Ping Chen
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Min Mao
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Chendan Wang
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Xu Zhang
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Xiaoyu Zhao
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Yuanyuan Gao
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Yankun Luo
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
| | - Yun Zhou
- Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, China
- Shanxi Genetic Engineering Center for Experimental Animal Models, Taiyuan, China
- Department of Nephrology, Shanxi Province Integrated Traditional and Western Medicine Hospital, Taiyuan, China
- *Correspondence: Yun Zhou,
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Efficacy of Traditional Chinese Medicine on Animal Model of IgA Nephropathy: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:6106993. [PMID: 36601331 PMCID: PMC9807304 DOI: 10.1155/2022/6106993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 09/23/2022] [Indexed: 12/27/2022]
Abstract
Objective Traditional Chinese medicine (TCM) has a long history in the treatment of Immunoglobulin A nephropathy (IgAN). A large number of animal experiments focused on the TCM treatment of IgAN are conducted every year. The evidence for these preclinical studies is not clear. This study summarized and evaluated the results of animal experiments on TCM treatment for IgAN. Methods We systematically searched animal studies from 6 databases from inception to August 30, 2022. We included Chinese studies from the key magazine of China technology. The quality of the included studies was evaluated with the SYRCLE animal experimental bias risk assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results Out of 832 records identified in the initial search, 30 studies were selected. The results indicated that, compared with the control group, the TCM treatment group improved 24 h urine protein (24 h-UP) level (standardized mean difference (SMD) 3.57, 95% confidence interval (CI) 4.48 to 2.66, P < 0.001), urine red blood cell (U-RBC) (SMD 13.66, 95% CI 17.99 to 9.32, P < 0.001), serum creatinine (Scr) (mean difference (MD) 10.89, 95% CI 17.00 to 4.77, P < 0.001), blood urea nitrogen (BUN) (MD 2.44, 95% CI 3.42 to 1.47, P < 0.001), tumor necrosis factor-α (TNF-α) (MD 171.28 to 95% CI 323.68 to 18.88, P=0.03), transforming growth factor-β1 (TGF-β) (SMD 4.02, 95% CI 7.26 to 0.77, P=0.02), matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1(MMP-9/TIMP-1) (MD 0.03, 95% CI 0.00 to 0.06, P=0.02), nephrin mRNA (SMD 3.39, 95% CI 2.59 to 4.18, P < 0.001). However, there is no difference in albumin level (MD 1.10, 95% CI 0.06 to 2.26, P=0.06) and interleukin-6 (IL-6) (MD 170.77, 95% CI 365.3 to 23.75, P=0.09). Conclusions TCM can improve 24 h-UP, U-RBC, Scr, BUN, MMP-9/TIMP-1, TNF-α, TGF-β, and nephrin mRNA of IgAN animal models. Moreover, there is a need for rigorous reporting of preclinical research methodology, which is essential to support the quality of preclinical research. Registration. This review was registered with a systematic review record CRD42020171404 in the PROSPERO database.
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Chen H, Qiu X, Wang J, Wei H. Pharmacists' role in multidisciplinary diagnosis and treatment in adverse reactions: A case report of interferon alfa-2b induced severe lupus. Medicine (Baltimore) 2022; 101:e31997. [PMID: 36550841 PMCID: PMC9771234 DOI: 10.1097/md.0000000000031997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
RATIONALE Various side effects of interferon alfa-2b (IFN-α2b) have been reported. However, no relevant research has been conducted on the identification and treatment scheme selection for IFN-α2b induced severe systemic lupus erythematosus (SLE). PATIENT CONCERNS A 41-years-old man with a long history of hepatitis B who developed severe active SLE after IFN-α2b therapy for 24 months, with complete and persistent remission of clinical and laboratory abnormalities after IFN-α2b withdrawal, was not observed. DIAGNOSIS The patient was diagnosed with interferon-associated lupus by a multidisciplinary team involving pharmacists, and lupus nephritis by renal biopsy. INTERVENTIONS Methylprednisolone (40 mg/day) with intravenous cyclophosphamide (600 mg/body weight) was initiated and the symptoms were partially relieved. Cyclophosphamide was increased from 600 mg to 850 mg at the pharmacist's recommendation. OUTCOMES The patient showed a favorable response to these therapies. LESSONS Clinical pharmacists collaborated with other members of the health care team to diagnose and treat adverse reactions, resulting in improved patient management.
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Affiliation(s)
- Hongxia Chen
- Department of pharmacy, Fudan University Huashan Hospital, Shanghai, China
- Department of clinical pharmacy, People’s Hospital of GuangXi Zhuang Autonomous Region, Nanning, Guangxi, China
- * Correspondence: Hongxia Chen, Department of clinical pharmacy, People’s Hospital of GuangXi Zhuang Autonomous Region, NO.6 Taoyuan Road, Nanning 530021, Guangxi, China (e-mail: )
| | - Xiaoyan Qiu
- Department of pharmacy, Fudan University Huashan Hospital, Shanghai, China
| | - Jingyi Wang
- Department of pharmacy, Fudan University Huashan Hospital, Shanghai, China
| | - Hualing Wei
- Department of clinical pharmacy, People’s Hospital of GuangXi Zhuang Autonomous Region, Nanning, Guangxi, China
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MacLeod CA, Gauthier I, Davenport MS, McGrath TA, Khan F, Dos Santos MP, McInnes MDF, Schieda N. Adverse Events Associated with Intra-Arterial Administration of Gadolinium-Based Contrast Agents: A Systematic Review and Meta-Analysis. J Vasc Interv Radiol 2022; 34:568-577.e10. [PMID: 36464013 DOI: 10.1016/j.jvir.2022.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 11/08/2022] [Accepted: 11/19/2022] [Indexed: 12/03/2022] Open
Abstract
PURPOSE To determine the risk of immediate hypersensitivity reactions (HRs), contrast-associated acute kidney injury (CA-AKI), nephrogenic systemic fibrosis (NSF), and gadolinium retention associated with use of intra-arterial gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from 1988 (GBCAs approved for clinical use) to March 2021 for studies reporting adverse events associated with intra-arterial administration of GBCAs. The number of adverse events and GBCA administrations were used to calculate incidence in individual studies, and results across studies were pooled using random-effects meta-analysis. RESULTS There were 72 studies (patients = 1,221) that reported on HR, 59 studies (patients = 1,142) that reported on CA-AKI, and 6 studies (patients = 291) that reported on NSF. No studies reported gadolinium retention as an outcome. Based on 5 events and 1,451 GBCA administrations, the incidence of HR per 100 administrations was 0.95 (95% CI, 0.52-1.51). Based on 90 events and 1,318 GBCA administrations, the incidence of CA-AKI per 100 administrations was 5.94 (95% CI, 3.92-8.34). Based on 7 events and 361 GBCA administrations, the incidence of NSF per 100 Group I GBCA administrations was 4.72 (95% CI, 0.35-13.70). There were no unconfounded NSF events after Group II GBCA administration. CONCLUSIONS HRs to intra-arterial administration of GBCAs are rare, with no serious reactions. Limited data demonstrate a higher-than-expected rate of CA-AKI; however, multiple confounding factors were noted. Thus, any causative link of CA-AKI to GBCA remains controversial. Also, severe physiologic reactions (including life-threatening arrhythmias) during coronary angiography have been reported.
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Affiliation(s)
- Chad A MacLeod
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Isabelle Gauthier
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Matthew S Davenport
- Department of Radiology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan
| | - Trevor A McGrath
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Faizan Khan
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | | | - Mathew D F McInnes
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Epidemiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Nicola Schieda
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
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Lv X, Wang J, Zhang L, Shao X, Lin Y, Liu H, Ma G, Li J, Zhou S, Yu P. Canagliflozin reverses Th1/Th2 imbalance and promotes podocyte autophagy in rats with membranous nephropathy. Front Immunol 2022; 13:993869. [PMID: 36531996 PMCID: PMC9751039 DOI: 10.3389/fimmu.2022.993869] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/15/2022] [Indexed: 12/04/2022] Open
Abstract
Idiopathic membranous nephropathy is the main cause of chronic kidney disease (CKD). Studies have shown sodium-glucose co-transporter 2 (SGLT2) inhibitors significantly delay renal outcomes in patients with CKD, but the exact mechanism remains unknown. In this study, we investigated the mechanism by which the SGLT2 inhibitor canagliflozin attenuates podocyte injury by reversing the imbalance in Helper T cell 1 (Th1)/Helper T cell 2 (Th2) in peripheral blood of rats with membranous nephropathy (MN). MN rats were gavaged with canagliflozin (10 mg/kg/d) and losartan (10 mg/kg/d), respectively, for eight weeks. Compared with the MN group, the urinary ratio of total protein and the creatinine levels of the canagliflozin group decreased significantly. Canagliflozin improved the glomerulus pathological damage, increased the expression levels of podocyte marker proteins. The protective effect of canagliflozin on kidneys was more obvious than that of losartan. Treatment with canagliflozin increased the proportion of Th1 cells by 2.3 times, decreased the proportion of Th2 cells by 68.5%, and significantly restrained the synthesis of immunoglobulin G1 in B-cells and glomerulus subepithelial immune complex deposition. Co-culture of B-cells derived from MN rats with podocytes triggered the activation of phosphorylation of mTOR and ULK1 of podocytes, inhibited podocyte autophagy and resulted in podocyte injury. B-cells derived from canagliflozin treatment rats reversed these effects above. In conclusion, canagliflozin exerts a protective effect on kidneys by reversing the imbalance in Th1/Th2 cells in MN rats and restoring the autophagy of podocytes inhibited by the abnormal immunoglobulin G secretion from B-cells.
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Affiliation(s)
- Xin Lv
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Wang
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
- Department of Nephrology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Li Zhang
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Xian Shao
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Yao Lin
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Hongyan Liu
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Guangyang Ma
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Jing Li
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Saijun Zhou
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
| | - Pei Yu
- NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China
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Tan J, Luo X, Yang J, Liu N, Jiang Z, Tang Y, Qin W. Clinicopathological characteristics and risk factors in elderly patients with biopsy-proven IgA nephropathy. Ren Fail 2022; 44:1026-1036. [PMID: 35766236 PMCID: PMC9246206 DOI: 10.1080/0886022x.2022.2087527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Immunoglobulin A nephropathy (IgAN) has been well studied among young people, but few data on clinicopathological characteristics, treatment response and outcomes for elderly IgAN patients are available. METHODS A cohort study of elderly IgAN patients was performed. The combined endpoints of renal outcome were a 50% decline in eGFR compared with the time of renal biopsy, end-stage kidney disease and/or death. Risk factors associated with poor renal outcomes were then determined. The benefits of immunosuppressant therapies were also evaluated by Kaplan-Meier survival curve analysis. RESULTS This study ultimately included 126 elderly patients with IgAN. Comparison between the endpoint and non-endpoint groups indicated that patients with poor outcomes had more severe clinical features, such as worse kidney function, severe hematuria and lower albumin levels. Cox regression analysis indicated that age (HR 1.15, 95% CI 1.02-1.29, p = 0.021), male gender (HR 9.71, 95% CI 1.00-97.56, p = 0.050), and urine red blood cells (HR 1.003, 95% CI 1.000-1.006, p = 0.029) were independent risk factors for poor renal outcome in elderly IgAN patients. To explore possible reasons accounting for the predictive value of age and sex, patients were divided into two groups based on these two variables. Patients in the geriatric group had lower serum albumin, estimated glomerular filtration rate, hemoglobin and aspartate aminotransferase levels than those in the quinquagenarian group. Male patients tended to have higher hemoglobin, higher alanine aminotransferase, and lower triglycerides and cholesterol levels than female patients. To investigate different treatment responses, patients were classified into two groups depending on treatment strategies (renin-angiotensin system inhibitors and immunosuppressive therapy), and the survival analysis indicated no significant difference in kidney outcome between the two groups (p > 0.05). This result still holds after adjusting for age, sex, eGFR, hematuria, and proteinuria. CONCLUSION Advanced age, male, and hematuria might be independently associated with poor kidney outcomes in elderly patients with IgAN. Immunosuppressive therapy might confer no overall benefit to older IgAN patients.
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Affiliation(s)
- Jiaxing Tan
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xinyao Luo
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Jiaqing Yang
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Nuozhou Liu
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Zheng Jiang
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.,West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Yi Tang
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wei Qin
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Ruo-Ji C, Fang X, Zhen-Shuang D, Yu-Lin Z, Zi-Li Z, Wei-Yuan L. Comparative efficacy of three regimens (cyclosporine, tacrolimus, and cyclophosphamide) combined with steroids for the treatment of idiopathic membranous nephropathy. Nefrologia 2022; 42:671-679. [PMID: 36402685 DOI: 10.1016/j.nefroe.2022.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 08/01/2021] [Indexed: 06/16/2023] Open
Abstract
INTRODUCTION AND OBJECTIVES To investigate the efficacy of combined immunosuppressive regimens of cyclosporine (CsA), tacrolimus (TAC), or cyclophosphamide (CTX) combined with steroids in the treatment of idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS A total of 150 biopsy-proven IMN patients were divided into three groups: CTX, TAC, and CsA groups (50 cases each). Patients received a selected regimen for 48 weeks. The efficacy (remission rate, 24h urinary protein, and serum albumin and creatinine) and safety (adverse events) profiles of administered regimens were evaluated at 12, 24 and 48 weeks. RESULTS At 12 weeks, the response rates for CsA, TAC, and CTX groups were 14%, 50%, and 22%, respectively. This increased to 74%, 84%, and 82%, respectively at 48 weeks. During follow-up, 24h urinary protein significantly reduced from baseline in all regimens (P<0.05), while serum albumin increased in TAC and CTX groups after 12 weeks (P<0.05), and CsA group at 48 weeks (P<0.05). No significant changes in serum creatinine levels were noted in all three regimens (P>0.05). Safety was comparable in all groups, with lower respiratory tract infection being the most frequent adverse event. CONCLUSIONS The combined regimens (i.e., TAC, CsA, and CTX) are effective in the treatment of patients with IMN at 48 weeks, while TAC and CTX might be more beneficial in terms of shortened time to remission and increased complete response rate.
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Affiliation(s)
- Chen Ruo-Ji
- Department of Nephrology, Jinjiang Municipal Hospital, Jinjiang, Fujian, China
| | - Xing Fang
- Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Du Zhen-Shuang
- Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Zhang Yu-Lin
- Department of Pediatric, Jinjiang Municipal Hospital, Jinjiang, Fujian, China
| | - Zheng Zi-Li
- Department of Nephrology, Jinjiang Municipal Hospital, Jinjiang, Fujian, China
| | - Lin Wei-Yuan
- Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
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Wang Y, Wang X, Yu J, Wu S, Xu Z, Sun W. Idiopathic membranous nephropathy with renal amyloidosis: A case report. Front Med (Lausanne) 2022; 9:986065. [PMID: 36388894 PMCID: PMC9659563 DOI: 10.3389/fmed.2022.986065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 10/12/2022] [Indexed: 11/22/2022] Open
Abstract
Background Immunoglobulin light chain amyloidosis is a clonal, non-proliferative plasma cell disorder, in which fragments of immunoglobulin light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma. Membranous nephropathy (MN) is a group of diseases characterized by deposition of immune complexes under the epithelial cells of glomerular basement and diffuse thickening of the basement membrane. Most patients with idiopathic MN (IMN) have been exposed to phospholipase A2 receptor (PLA2R) antigen, and anti-PLA2R antibodies that attack podocytes can be detected in their blood. IMN combined with amyloidosis nephropathy without secondary factors is rare. The present study describes a patient with IMN combined with immunoglobulin light chain amyloidosis nephropathy. Case report A 39-year-old man was admitted to our hospital because of weight loss and edema. His clinical manifestation was nephrotic syndrome. Renal pathology revealed MN. A positive Congo red staining and the pathognomonic apple-green birefringence under cross-polarized light were considered to be associated with amyloid nephropathy. Immunofluorescence showed that λ light chain was positive. Heavy chain deposition disease and amyloid-associated protein amyloidosis were excluded by immunofluorescence and immunohistochemistry, respectively. Subsequent examinations showed that his serum was negative for antibodies against the PLA2R, but PLA2R was present in renal tissue. The final diagnosis was IMN with light chain amyloid nephropathy. Conclusion Renal amyloidosis accompanied by IMN is uncommon. Attention should be paid to the subtype of the disease and the exclusion of secondary factors. Perfect clinical and pathological examination are helpful for the classification and staging of the disease. Congo red staining, light microscopy, immunofluorescence, immunohistochemistry, electron microscopic examination, pathological tissue staining for PLA2R antigen and testing for anti-PLA2R antibody in serum are helpful.
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Affiliation(s)
- Yue Wang
- Department of Nephrology, The First Affiliated Hospital of Jilin University, Changchun, China
| | - Xueyao Wang
- Department of Nephrology, The First Affiliated Hospital of Jilin University, Changchun, China
| | - Jinyu Yu
- Second Department of Urology, The First Affiliated Hospital of Jilin University, Changchun, China
| | - Shan Wu
- Department of Nephrology, The First Affiliated Hospital of Jilin University, Changchun, China
| | - Zhonggao Xu
- Department of Nephrology, The First Affiliated Hospital of Jilin University, Changchun, China
| | - Weixia Sun
- Department of Nephrology, The First Affiliated Hospital of Jilin University, Changchun, China
- *Correspondence: Weixia Sun,
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Chauvet S, Hauer JJ, Petitprez F, Rabant M, Martins PV, Baudouin V, Delmas Y, Jourde-Chiche N, Cez A, Ribes D, Cloarec S, Servais A, Zaidan M, Daugas E, Delahousse M, Wynckel A, Ryckewaert A, Sellier-Leclerc AL, Boyer O, Thervet E, Karras A, Smith RJH, Frémeaux-Bacchi V. Results from a nationwide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy. Kidney Int 2022; 102:904-916. [PMID: 35752323 PMCID: PMC10588728 DOI: 10.1016/j.kint.2022.05.027] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 04/14/2022] [Accepted: 05/26/2022] [Indexed: 10/17/2022]
Abstract
C3 glomerulopathy (C3G) is a rare complement-mediated disease. Specific treatments are not yet available and factors predictive of kidney survival such as age, kidney function and proteinuria are not specific to C3G. The prognostic value of biomarkers of complement activation, which are pathognomonic of the diseases, remains unknown. In a large cohort of 165 patients from the French National registry, we retrospectively assess the prognostic value of C3, soluble C5b-9 (sC5b-9), C3 nephritic factor, and rare disease-predicting variants in complement genes in predicting clinical outcome of patients. By multivariate analysis age (adult onset), reduced kidney function (defined by estimated glomerular filtration rate under 60ml/min) and presence of rare disease-predicting variants in complement genes predicted risk of progression to kidney failure. Moreover, by multivariate analysis, normal C3/high sC5b-9 levels or low C3/normal sC5b-9 levels remained independently associated with a worse kidney prognosis, with the relative risk 3.7- and 8-times higher, respectively. Subgroup analysis indicated that the complement biomarker profiles independently correlated to kidney prognosis in patients with adult but not pediatric onset. In this subgroup, we showed that profiles of biomarkers C3 and/or sC5b-9 correlated with intra glomerular inflammation and may explain kidney outcomes. In children, only the presence of rare disease-predicting variants correlated with kidney survival. Thus, in an adult population, we propose a three-point C3G prognostic score based on biomarker profiles at risk, estimated glomerular filtration rate at presentation and genetic findings, which may help stratify adult patients into subgroups that require close monitoring and more aggressive therapy.
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Affiliation(s)
- Sophie Chauvet
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM UMRS1138, Centre de Recherche des Cordeliers, Team "Inflammation, Complement and cancer", Paris, France; Paris Cité University, Paris, France.
| | - Jill J Hauer
- Molecular Otolaryngology and Renal Research Laboratories, University of Iowa, Iowa City, Iowa, USA
| | - Florent Petitprez
- Programme Cartes d'Identités des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France
| | - Marion Rabant
- Department of Renal Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France
| | - Paula Vieira Martins
- Department of Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Véronique Baudouin
- Department of Pediatric Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France
| | - Yahsou Delmas
- Department of Nephrology, CH Bordeaux, Bordeaux, France
| | | | - Alexandre Cez
- Department of Nephrology, Tenon Hospital, Assistance Publique-hopitaux de Paris, Paris, France
| | - David Ribes
- Department of Nephrology, CHU Toulouse, Toulouse, France
| | - Sylvie Cloarec
- Department of Pediatric Nephrology, CHU Tours, Tours, France
| | - Aude Servais
- Department of Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France
| | - Mohamad Zaidan
- Department of Nephrology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France
| | - Eric Daugas
- Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Department of Nephrology, Paris, France
| | | | | | | | | | - Olivia Boyer
- Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Department of Pediatric Nephrology, Paris, France
| | - Eric Thervet
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Alexandre Karras
- Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Richard J H Smith
- Molecular Otolaryngology and Renal Research Laboratories, University of Iowa, Iowa City, Iowa, USA
| | - Véronique Frémeaux-Bacchi
- INSERM UMRS1138, Centre de Recherche des Cordeliers, Team "Inflammation, Complement and cancer", Paris, France; Department of Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
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Chen M, Zhang P, Li L, Yu Z, Liu N, Wang L. Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis. Emerg Med Int 2022; 2022:5314105. [PMID: 36212998 PMCID: PMC9546686 DOI: 10.1155/2022/5314105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/09/2022] [Accepted: 09/16/2022] [Indexed: 11/18/2022] Open
Abstract
Background IgA nephropathy (IgAN) is currently the most common primary glomerular disease, accounting for approximately 36.7% to 58.2% of primary glomerular disease in kidney biopsies in China. Definitive diagnosis depends on immunopathological examination of the kidney. The prognosis of this disease was generally considered to be good, but recent studies have found that about half of patients can progress to end-stage renal disease within 30 years of onset. Because the pathogenesis is unknown, there is no specific treatment. Objective To evaluate the efficacy and safety of glycosides of Tripterygium wilfordii (GTW) in combination with renin-angiotensin system (RAS) inhibitors for the treatment of IgAN. Methods Search Embase, Pubmed, Cochrane, CNKI, Web of Science, Wanfang, and VIP for all randomized controlled trials (RCTs) on treating IgAN with RASI from the self-built database to December 2021. Relevant data were searched and collected separately by two reviewers. The Cochrane risk of bias model was used for quality assessment, and RevMan 5.3 was used for data analysis. Results Thirteen Chinese publications with a total of 958 patients were finally included. There was no statistically significant difference in baseline information (including laboratory data and clinical parameters) between the two groups of patients. The urine protein quantification in both groups showed a significant decreasing trend as the treatment duration increased. At 3, 6, 9, and 12 months after treatment, urine protein was significantly lower than the baseline value in both the observation and control groups (P < 0.05). During the follow-up period, there was no statistical difference in blood creatinine (Scr) and eGFR values between the two groups compared with the baseline values (P > 0.05). Patients with CKD stage 2 achieved a higher remission rate compared with patients with CKD stage 3, with a statistically significant difference (P < 0.05), and the difference between the two groups was not significant for patients in the same stage. There was no statistically significant difference in the total effective rate between the two groups (P > 0.05). During the follow-up period, there was no statistically significant difference in urine protein quantification, Scr, and eGFR between the two groups. In terms of the incidence of adverse reactions, the observation group was less than the control group, and there was a significant difference between the two groups (P < 0.05). Conclusion GTW combined with RASI is one of the safe and effective treatment modes for IgAN nephropathy. It can not only effectively reduce the excretion of urinary protein in patients and delay the progression of chronic kidney disease but also has less serious side effects and is well tolerated by patients, so it can be a new choice of therapeutic drugs for this group of patients.
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Affiliation(s)
- Ming Chen
- Heilongjiang Academy of Traditional Chinese Medicine, Department of Nephropathy, Heilongjiang 150036, China
| | - Peiqing Zhang
- Heilongjiang Academy of Traditional Chinese Medicine, Department of Nephropathy, Heilongjiang 150036, China
| | - Lianhua Li
- Heilongjiang Academy of Traditional Chinese Medicine, Department of Nephropathy, Heilongjiang 150036, China
| | - Zhuo Yu
- Heilongjiang Academy of Traditional Chinese Medicine, Department of Nephropathy, Heilongjiang 150036, China
| | - Na Liu
- Heilongjiang Academy of Traditional Chinese Medicine, Department of Nephropathy, Heilongjiang 150036, China
| | - Lifan Wang
- Heilongjiang Academy of Traditional Chinese Medicine, Department of Nephropathy, Heilongjiang 150036, China
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Structural modeling for Oxford histological classifications of immunoglobulin A nephropathy. PLoS One 2022; 17:e0268731. [PMID: 36084046 PMCID: PMC9462802 DOI: 10.1371/journal.pone.0268731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/16/2022] [Indexed: 12/03/2022] Open
Abstract
In immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria, eGFR, mean arterial pressure (MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy (ST) and renin–angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the model’s goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity and active crescent (C) had an attenuating indirect effect via ST. Segmental sclerosis (S) had an attenuating indirect effect via eGFR and mesangial hypercellularity (M) had accelerative indirect effect for RFD via proteinuria. Moreover, M and C had accelerative indirect effect via proteinuria, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR or MAP at biopsy, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.
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Yang N, Li L, He H, Guo X, Yuan X, Li Z, Wang W, Qin B, Du X, Zhang X, Chen S, Lin H. Positive association of serum FUT8 activity with renal tubulointerstitial injury in IgA nephropathy patients. Immun Inflamm Dis 2022; 10:e686. [PMID: 36039648 PMCID: PMC9425009 DOI: 10.1002/iid3.686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/25/2022] [Accepted: 07/26/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND α-1,6 Fucosyltransferase (FUT8) appears to play an essential role in the pathogenesis of renal fibrosis. However, it remained unknown whether FUT8 also contributed to renal fibrosis in immunoglobulin A nephropathy (IgAN). In the present study, we explored the association of serum FUT8 activity with renal tubulointerstitial injury in IgAN patients. METHODS Serum FUT8 activity was measured in 135 IgAN patients and 68 healthy controls from January 2016 to December 2018. The relationships of serum FUT8 activity with clinical and pathological features were analyzed. RESULTS Relative to healthy controls, IgAN patients had significantly higher serum FUT8 activity and upregulation of renal FUT8 protein (p < .05). Among IgAN patients, there was a positive correlation of serum FUT8 activity with renal FUT8 protein expression (p < .05). Multivariable logistic regression analyses showed that serum FUT8 activity was significantly associated with serum creatinine and eGFR (p < .05). Based on a cut-off value determined from ROC curve analysis, we divided IgAN patients into a low serum FUT8 activity group (≤12.2 pmol/h/mL, n = 40) and a high serum FUT8 activity group (>12.2 pmol/h/ml, n = 95). The high serum FUT8 activity group had a higher Oxford T score, increased inflammatory cell infiltration, more severe fibrosis and poor renal function (p < .05). CONCLUSION Serum FUT8 activity was positive association with renal tubulointerstitial injury in IgAN patients.
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Affiliation(s)
- Ning Yang
- Graduate School of Dalian Medical UniversityDalian Medical UniversityDalianChina
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Long‐kai Li
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Hui He
- Graduate School of Dalian Medical UniversityDalian Medical UniversityDalianChina
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Xia‐nan Guo
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Xue‐feng Yuan
- Graduate School of Dalian Medical UniversityDalian Medical UniversityDalianChina
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Zhi‐tong Li
- Graduate School of Dalian Medical UniversityDalian Medical UniversityDalianChina
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Wei‐dong Wang
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Biao‐jie Qin
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Xiang‐ning Du
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Xu Zhang
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Shu‐ni Chen
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Hong‐li Lin
- Department of Nephrology, Liaoning Translational Medicine Center of NephrologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
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Liu J, Li X, Huang T, Xu G. Efficacy and safety of 12 immunosuppressive agents for idiopathic membranous nephropathy in adults: A pairwise and network meta-analysis. Front Pharmacol 2022; 13:917532. [PMID: 35959430 PMCID: PMC9358043 DOI: 10.3389/fphar.2022.917532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/27/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants do not have final conclusion. Thus, a pairwise and network meta-analysis (NMA) was carried out to seek the most recommended therapeutic schedule for patients with IMN. Methods: Randomized controlled trials (RCTs) including cyclophosphamide (CTX), mycophenolate mofetil (MMF), tacrolimus-combined mycophenolate mofetil (TAC + MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CH), azathioprine (AZA), adrenocorticotropic hormone (ACTH), non-immunosuppressive therapies (CON), steroids (STE), mizoribine (MZB), and rituximab (RIT) for patients with IMN were checked. Risk ratios (RRs) and standard mean difference (SMD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Total remission (TR) and 24-h urine total protein (24-h UTP) were compared using pairwise and NMA. Then interventions were ranked on the basis of the surface under the cumulative ranking curve (SUCRA). Results: Our study finally included 51 RCTs and 12 different immunosuppressants. Compared with the CON group, most regimens demonstrated better therapeutic effect in TR, with RR of 2.1 (95% CI) (1.5–2.9) for TAC, 1.9 (1.3–2.8) for RIT, 2.5 (1.2–5.2) for TAC + MMF, 1.9 (1.4–2.7) for CH, 1.8 (1.4–2.4) for CTX, 2.2 (1.0–4.7) for ACTH, 1.6 (1.2–2.1) for CsA, 1.6 (1.0–2.5) for LEF, and 1.6 (1.1–2.2) for MMF. In terms of 24-h UTP, TAC (SMD, −2.3 (95% CI −3.5 to −1.1)), CTX (SMD, −1.7 (95% CI −2.8 to −0.59)), RIT (SMD, −1.8 (95% CI −3.5 to −0.11)), CH (SMD, −2.4 (95% CI −4.3 to −0.49)), AZA (SMD, −−4.2 (95% CI −7.7 to −0.68)), and CsA (SMD, −1.7 (95% CI −3 to −0.49)) were significantly superior than the CON group. As for adverse effects (AEs), infections, nausea, emesia, myelosuppression, and glucose intolerance were the collective adverse events for most immunosuppressants. Conclusion: This study indicates that TAC + MMF performed the best in terms of TR, and TAC shows the best effectiveness on 24-h UTP compared with other regimens. On the contrary, there seems to be little advantage on STE alone, LEF, AZA, and MZB in treating patients with IMN compared with CON. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021287013]
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Population Pharmacokinetic Evaluation with External Validation of Tacrolimus in Chinese Primary Nephrotic Syndrome Patients. Pharm Res 2022; 39:1907-1920. [PMID: 35650450 DOI: 10.1007/s11095-022-03273-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/22/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE The generalizability of numerous tacrolimus population pharmacokinetic (popPK) models constructed to promote optimal tacrolimus dosing in patients with primary nephrotic syndrome (PNS) is unclear. This study aimed to evaluate the predictive performance of published tacrolimus popPK models for PNS patients with an external data set. METHODS We prospectively collected 223 concentrations from 50 Chinese adult patients with PNS who were undergoing tacrolimus treatment. Data on published tacrolimus popPK models for adults and children with PNS were extracted from the literature. Model predictability was evaluated with prediction-based and simulation-based diagnostics and Bayesian forecasting. RESULTS In prediction-based evaluation, none of the 11 identified published popPK models of tacrolimus had met a predefined criteria of a mean prediction error ≤ ± 20%, and the prediction error within ± 30% of the identified models didn't exceed 50%. Simulation-based diagnostics also indicated unsatisfactory predictability. Bayesian forecasting demonstrated amelioration in the model predictability with the inclusion of 2-3 prior observations. Moreover, the predictive performance of nonlinear models was not better than that of one-compartment models. CONCLUSIONS The prediction of tacrolimus concentrations for patients with PNS remains challenging; published models are not applicable for extrapolation to other hospitals. Bayesian forecasting significantly improved model predictability and thereby helped to individualize tacrolimus dosing.
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Shao B, Qu Y, Zhang W, Zhan H, Li Z, Han X, Ma M, Du Z. Machine Learning-Based Prediction Method for Tremors Induced by Tacrolimus in the Treatment of Nephrotic Syndrome. Front Pharmacol 2022; 13:708610. [PMID: 35571087 PMCID: PMC9091175 DOI: 10.3389/fphar.2022.708610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 03/25/2022] [Indexed: 11/15/2022] Open
Abstract
Tremors have been reported even with a low dose of tacrolimus in patients with nephrotic syndrome and are responsible for hampering the day-to-day work of young active patients with nephrotic syndrome. This study proposes a neural network model based on seven variables to predict the development of tremors following tacrolimus. The sensitivity and specificity of this algorithm are high. A total of 252 patients were included in this study, out of which 39 (15.5%) experienced tremors, 181 patients (including 32 patients who experienced tremors) were randomly assigned to a training dataset, and the remaining were assigned to an external validation set. We used a recursive feature elimination algorithm to train the training dataset, in turn, through 10-fold cross-validation. The classification performance of the classifer was then used as the evaluation criterion for these subsets to find the subset of optimal features. A neural network was used as a classification algorithm to accurately predict tremors using the subset of optimal features. This model was subsequently tested in the validation dataset. The subset of optimal features contained seven variables (creatinine, D-dimer, total protein, calcium ion, platelet distribution width, serum kalium, and fibrinogen), and the highest accuracy obtained was 0.8288. The neural network model based on these seven variables obtained an area under the curve (AUC) value of 0.9726, an accuracy of 0.9345, a sensitivity of 0.9712, and a specificity of 0.7586 in the training set. Meanwhile, the external validation achieved an accuracy of 0.8214, a sensitivity of 0.8378, and a specificity of 0.7000 in the validation dataset. This model was capable of predicting tremors caused by tacrolimus with an excellent degree of accuracy, which can be beneficial in the treatment of nephrotic syndrome patients.
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Affiliation(s)
- Bing Shao
- Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University (Key Laboratory of Medications Research, College of Heilongjiang Province), Harbin, China.,School of Pharmacy, Harbin Medical University, Harbin, China
| | - Youyang Qu
- Neurology Department, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Wei Zhang
- Nephrology Department, The Second Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Haihe Zhan
- Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University (Key Laboratory of Medications Research, College of Heilongjiang Province), Harbin, China
| | - Zerong Li
- Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University (Key Laboratory of Medications Research, College of Heilongjiang Province), Harbin, China
| | - Xingyu Han
- Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University (Key Laboratory of Medications Research, College of Heilongjiang Province), Harbin, China.,School of Pharmacy, Harbin Medical University, Harbin, China
| | - Mengchao Ma
- School of Pharmacy, Harbin Medical University, Harbin, China
| | - Zhimin Du
- Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University (Key Laboratory of Medications Research, College of Heilongjiang Province), Harbin, China.,School of Pharmacy, Harbin Medical University, Harbin, China.,State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China
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