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Wang X, Deng Z, Wang Y. IgG expressed by renal tubular epithelial cells in epithelial mesenchymal transformation and interstitial fibrosis in diabetic kidney disease. Ren Fail 2025; 47:2458764. [PMID: 39901448 PMCID: PMC11795750 DOI: 10.1080/0886022x.2025.2458764] [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: 09/11/2024] [Revised: 01/20/2025] [Accepted: 01/21/2025] [Indexed: 02/05/2025] Open
Abstract
Studies have reported that immunoglobulin G (IgG) "deposited" in the basement membrane of renal tubules is associated with tubulointerstitial damage in patients with diabetic kidney disease (DKD). Our previous study found that renal tubular epithelial cells (RTECs) can express and secrete IgG (RTEC-IgG) which may be associated with fibrosis. The present study aimed to explore the role of RTEC-IgG in renal tubulointerstitial fibrosis (TIF) in DKD. The results showed that RTEC-IgG expression was up-regulated in the renal tubulointerstitium of DKD patients and was associated with worse kidney function, more severe anemia, and higher interstitial fibrosis and tubular atrophy (IFTA) scores, and positively correlated with tubular epithelial mesenchymal transition (EMT) and TIF. IgG expression was also enhanced in the renal tubulointerstitium of DKD mice, which was positively correlated with TIF. High glucose induced an over expression of IgG in human renal tubular epithelial cells, and knockdown of IgG with siRNA relieved the expression of α-smooth muscle actin (SMA), collagen IV, fibronectin, and transforming growth factor (TGF)-β1 under high glucose conditions. In conclusion, our study suggests that RTEC-IgG is involved in the development of DKD by promoting EMT and interstitial fibrosis via TGF-β1.
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Affiliation(s)
- Xinyao Wang
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Zhenling Deng
- Department of Nephrology, Peking University Third Hospital, Beijing, China
| | - Yue Wang
- Department of Nephrology, Peking University Third Hospital, Beijing, China
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Li M, Chang D, Zhao Y, Wu L, Tan Y, Zhao M, Tang SCW, Chen M. Urinary renal tubular epithelial cells and casts as predictors of renal outcomes in patients with biopsy-proven diabetic nephropathy. J Nephrol 2024; 37:2233-2242. [PMID: 39031241 DOI: 10.1007/s40620-024-01995-8] [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: 02/04/2024] [Accepted: 05/20/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND Urine sediment examination is a time-tested and non-invasive diagnostic tool. This study investigated the characteristics of urine sediment and its association with severity and renal outcomes in diabetic nephropathy (DN) patients. METHODS A total of 201 biopsy-proven diabetic nephropathy patients (according to the pathological classification of diabetic nephropathy proposed by the Renal Pathology Society in 2010) who underwent manual urine sediment microscopic examination were included. We compared the clinicopathological characteristics of diabetic nephropathy patients with and without urinary renal tubular epithelial cells (RTECs) or renal tubular epithelial cell casts. The predictive value of urinary renal tubular epithelial cells or renal tubular epithelial cell casts for renal outcomes in diabetic nephropathy was analyzed. RESULTS Fifty of 201 (24.9%) diabetic nephropathy patients had renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment. Diabetic nephropathy patients with renal tubular epithelial cells or renal tubular epithelial cell casts in urine sediment had a significantly higher level of proteinuria [6.0 (3.1, 9.7) vs. 3.6 (1.8, 6.8) g/24 h, p = 0.001], higher serum creatinine [227.9 (151.6, 338.1) vs. 177.0 (104.4, 288.4) μmol/L, p = 0.016] and lower estimated glomerular filtration rate (eGFR) [25.8 (15.8, 44.8) vs. 35.7 (19.9, 65.0) mL/min/1.73 m2, p = 0.025] than those without. Cox regression analysis demonstrated that the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was independently associated with the development of end-stage kidney disease (ESKD) in diabetic nephropathy patients [HR 1.670, 95% CI (1.042, 2.676), p = 0.033]. Adding the presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts to the predictive model could improve the effectiveness of the model for predicting the risk of ESKD within one year after renal biopsy. CONCLUSIONS The presence of urinary renal tubular epithelial cells or renal tubular epithelial cell casts was associated with more severe kidney injury and worse renal outcomes in patients with diabetic nephropathy, thus perhaps providing a noninvasive biomarker for predicting diabetic nephropathy.
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Affiliation(s)
- Mengrui Li
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Dongyuan Chang
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China.
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Yiyang Zhao
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Liang Wu
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Ying Tan
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Minghui Zhao
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
- Peking-Tsinghua Center for Life Sciences, Beijing, China
| | - Sydney Chi Wai Tang
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
| | - Min Chen
- Renal Division, Department of Medicine, 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, Ministry of Education, Peking University, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
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Zhou T, Fang YL, Tian TT, Wang GX. Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies. World J Diabetes 2024; 15:1111-1121. [PMID: 38983817 PMCID: PMC11229953 DOI: 10.4239/wjd.v15.i6.1111] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/29/2024] [Accepted: 04/15/2024] [Indexed: 06/11/2024] Open
Abstract
Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
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Affiliation(s)
- Tong Zhou
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
- Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
- National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Jilin University, Changchun 130021, Jilin Province, China
| | - Yi-Lin Fang
- Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
- National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Jilin University, Changchun 130021, Jilin Province, China
| | - Tian-Tian Tian
- School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Gui-Xia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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Hu Q, Yang Q, Gao H, Tian J, Che G. Immunoglobulin heavy constant gamma 1 silencing decreases tonicity-responsive enhancer-binding protein expression to alleviate diabetic nephropathy. J Diabetes Investig 2024; 15:572-583. [PMID: 38268239 PMCID: PMC11060157 DOI: 10.1111/jdi.14144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 12/14/2023] [Accepted: 12/21/2023] [Indexed: 01/26/2024] Open
Abstract
AIMS/INTRODUCTION The molecular mechanisms of diabetic nephropathy (DN) are poorly identified. However, the advantage of an increasing amount on microarray data of diabetic nephropathy intrigued us to explore the mechanisms based on bioinformatics prediction for diabetic nephropathy. MATERIALS AND METHODS Bioinformatics analysis was conducted to screen the hub genes associated with diabetic nephropathy. The average human renal tubular epithelial cells were exposed to high glucose (HG) to generate an in vitro cell model. In addition, a mouse model of diabetic nephropathy was established using a high-fat diet and streptozotocin injection. Finally, the shRNA targeting immunoglobulin heavy constant gamma 1 (IGHG1) was introduced in vitro and in vivo to illustrate its effect on downstream factors and on the development diabetic nephropathy. RESULTS Bioinformatics analysis revealed that IGHG1, TRIM11 (tripartite motif protein 11), and TonEBP are highly expressed in diabetic nephropathy. In vitro cell experiments demonstrated that IGHG1 positively regulates the expression of TRIM11 and TonEBP (tonicity-responsive enhancer binding protein) in HK2 cells treated with high glucose. Furthermore, TRIM11 upregulates the expression of TonEBP through activation of the MEK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) signaling pathway in HK2 cells treated with high glucose. In vivo, animal experiments further confirmed that silencing IGHG1 could prevent the occurrence and development of diabetic nephropathy. CONCLUSION The silencing of IGHG1 alleviated diabetic nephropathy by inhibiting the TRIM11/MEK/ERK axis and by downregulating TonEBP.
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Affiliation(s)
- Qibo Hu
- Department of PediatricsThe Second Hospital of JiLin UniversityChangchunChina
| | - Qingxiao Yang
- Department of NeurosurgeryThe Second Hospital of JiLin UniversityChangchunChina
| | - Hang Gao
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of MedicineJiLin UniversityChangchunChina
| | - Jing Tian
- Department of PediatricsThe Second Hospital of JiLin UniversityChangchunChina
| | - Guanghua Che
- Department of PediatricsThe Second Hospital of JiLin UniversityChangchunChina
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Kurata S, Nawata A, Morinishi T, Ohta K, Katafuchi E, Hisano S, Tanaka S, Hisaoka M, Koike J, Nishikomori R, Nakayama T. Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS. Ann Diagn Pathol 2023; 66:152154. [PMID: 37216712 DOI: 10.1016/j.anndiagpath.2023.152154] [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: 02/27/2023] [Revised: 04/28/2023] [Accepted: 05/02/2023] [Indexed: 05/24/2023]
Abstract
Immunofluorescent deposition of immunoglobulin G (IgG) in the tubular basement membrane (TBM) has been evaluated in the diagnosis of various diseases; however, few studies have investigated the immunofluorescence of acute tubular injury (ATI). Herein, we attempted to clarify IgG expression in the proximal tubular epithelium and TBM in ATI due to various causes. Patients with ATI with nephrotic-range proteinuria, including focal segmental glomerulosclerosis (FSGS, n = 18) and minimal change nephrotic syndrome (MCNS, n = 8), ATI with ischemia (n = 6), and drug-induced ATI (n = 7), were enrolled. ATI was evaluated by light microscopy. CD15 and IgG double staining and IgG subclass staining were performed to evaluate immunoglobulin deposition in the proximal tubular epithelium and TBM. IgG deposition was identified in the proximal tubules only in the FSGS group. Furthermore, IgG deposition in the TBM was observed in the FSGS group showing severe ATI. IgG3 was predominantly deposited by the IgG subclass study. Our results indicate that IgG deposition in the proximal tubular epithelium and TBM suggests the leaking of IgG from the glomerular filtration barrier and its reabsorption by proximal tubules, which may predict disruption of the glomerular size barrier, including subclinical FSGS. FSGS with ATI should be included as a differential diagnosis when IgG deposition in TBM is observed.
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Affiliation(s)
- Satoko Kurata
- Department of Pediatrics and Child Health, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan; Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Aya Nawata
- Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
| | - Takuya Morinishi
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
| | - Keisuke Ohta
- Advanced Imaging Research Center, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan
| | - Eisuke Katafuchi
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Satoshi Hisano
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Seiji Tanaka
- Department of Pediatrics and Child Health, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan
| | - Masanori Hisaoka
- Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Junki Koike
- Department of Pathology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
| | - Ryuta Nishikomori
- Department of Pediatrics and Child Health, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan
| | - Toshiyuki Nakayama
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
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Sun Y, Ren Y, Lan P, Yu X, Feng J, Hao D, Xie L. Clinico-pathological features of diabetic and non-diabetic renal diseases in type 2 diabetic patients: a retrospective study from a 10-year experience in a single center. Int Urol Nephrol 2023; 55:2303-2312. [PMID: 36879071 PMCID: PMC10406681 DOI: 10.1007/s11255-023-03478-4] [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: 11/14/2020] [Accepted: 01/19/2023] [Indexed: 03/08/2023]
Abstract
AIM To compare clinical and pathological characteristics as well as prognosis between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) so as to explore potential diagnostic criteria of DN and provide some guidance for the treatment of type 2 diabetes mellitus (T2DM) patients with kidney involvement. METHODS T2DM patients with renal impairment who underwent kidney biopsy were included in this study, who were classified into 3 groups (DN, NDRD, DN with NDRD) based on their renal pathological diagnosis. Baseline clinical characteristics as well as follow-up data were collected and analyzed among 3 groups. Logistic regression was performed to determine the best predictors for DN diagnosis. Additional 34 MN patients without diabetes were enrolled by propensity score matching method to compare serum PLA2R antibody titer and kidney outcomes between diabetic MN patients and MN alone. RESULTS Among 365 patients with type 2 diabetes who underwent kidney biopsy, 179 (49.0%) patients were diagnosed with NDRD alone and 37 (10.1%) patients with NDRD combined DN. Risk factors for DN development in T2DM patients were longer time since diabetes diagnosis, higher level of serum creatinine, absence of hematuria and presence of diabetic retinopathy by multivariate analysis. Lower rate of proteinuria remission and higher risk of renal progression were observed in DN group compared with NDRD group. Membranous nephropathy was the most common NDRD in diabetic patients. There was no difference in serum PLA2R antibody positiveness or titer between MN patients with or without T2DM. There was lower remission rate but similar renal progression in diabetic MN when age, gender, baseline eGFR, albuminuria and IFTA score were adjusted. CONCLUSIONS Non-diabetic renal disease is not uncommon in T2DM patients with renal impairment, which has better prognosis with proper treatment. Coexisting diabetic status does not exert negative impact on renal progression in MN patients, and immunosuppressive agents should be administered when necessary.
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Affiliation(s)
- Yuemeng Sun
- Department of Nephrology, Xi'an People's Hospital (Xi'an Forth Hospital), Xincheng District Jiefang Road 21, Xi'an, 710001, Shannxi, China
| | - Yawei Ren
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Yanta Western road 227, Xi'an, 710061, Shaanxi, China
| | - Ping Lan
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Yanta Western road 227, Xi'an, 710061, Shaanxi, China
| | - Xiaoyang Yu
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Yanta Western road 227, Xi'an, 710061, Shaanxi, China
| | - Jie Feng
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Yanta Western road 227, Xi'an, 710061, Shaanxi, China
| | - Dapeng Hao
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Yanta Western road 227, Xi'an, 710061, Shaanxi, China
| | - Liyi Xie
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Yanta Western road 227, Xi'an, 710061, Shaanxi, China.
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Tang X, Wan F, Zhu Q, Ye T, Jiang X, Yang H. IgG subclass deposition in diabetic nephropathy. Eur J Med Res 2022; 27:147. [PMID: 35953864 PMCID: PMC9367106 DOI: 10.1186/s40001-022-00779-9] [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: 05/21/2022] [Accepted: 08/03/2022] [Indexed: 11/21/2022] Open
Abstract
Purpose This study aimed to analyze the distribution of IgG subclass in diabetic nephropathy (DN) and its association with clinicopathological features. Methods This is a single-center retrospective study enrolling 108 patients with biopsy-proven DN. Immunofluorescence and immunohistochemistry staining were applied, and clinicopathological features and renal outcomes were compared between patients with different patterns or categories of IgG subclass deposition. Results Both IgG and its subclasses colocalized with collagen IV α5 on glomerular basement membrane (GBM) and some of tubular basement membrane (TBM). IgG1 and the Mixed type were two predominant types of deposition, no matter on GBM or TBM, and IgG1 showed a much higher deposition rate on GBM than that on TBM (P = 0.004). IgG subclass deposit on multi-location was more associated with a shorter duration of nephropathy and severer tubular interstitial injury (P < 0.05). The mixed type of IgG subclass deposit on GBM was merely associated with higher levels of proteinuria, whereas the deposition on TBM was more associated with higher levels of proteinuria, lower levels of albumin, more KIM-1 positive area, and thicker TBM (P < 0.05). Survival analysis revealed that none of the pattern or the category of IgG subclass deposit was a risk factor or a renal outcome indicator. Conclusions IgG subclass was selectively deposited along GBM and/or TBM in DN, and the mixed type of IgG subclass deposition on TBM had more clinical significance than the isotype and that on GBM. IgG subclass deposition is merely a manifestation or a consequence rather than a cause in DN.
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Affiliation(s)
- Xuanli Tang
- Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Feng Wan
- Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Qin Zhu
- Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Tian Ye
- Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Xue Jiang
- Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China.
| | - Haichun Yang
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
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Abdou AE, Anani HAA, Ibrahim HF, Ebrahem EE, Seliem N, Youssef EMI, Ghoraba NM, Hassan AS, Ramadan MAA, Mahmoud E, Issa S, Maghraby HM, Abdelrahman EK, Hassan HAM. Urinary IgG, serum CX3CL1 and miRNA-152-3p: as predictors of nephropathy in Egyptian type 2 diabetic patients. Tissue Barriers 2021; 10:1994823. [PMID: 34689723 DOI: 10.1080/21688370.2021.1994823] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
The purpose of this study was to assess the role of urinary IgG, serum CX3CL1 and miRNA 152-3p levels as predictors of nephropathy in type 2 Egyptian diabetic patients. Sixty type 2 diabetic patients and twenty healthy controls were enrolled in a cross-sectional study. Then they were grouped into: three groups based upon urine albumin excretion (UAE). The expression of miRNA 152-3p in serum was measured using quantitative polymerase chain reaction (RTq-PCR). Serum CX3CL1 and urinary IgG concentrations were measured by ELISA. RTq-PCR revealed that serum miRNA-152-3p levels in patients were significantly higher than in controls. There was significant differences between group with normoalbuminuria and groups with diabetic nephropathy DN as regard to age, duration of nephropathy, Albumin/Creatinine ratio (A/C ratio), creatinine, urine IgG, CX3CL1 and HbA1c. In diabetic patients, there was a significant positive correlation between miRNA-152-3p levels and disease duration only as well as significant positive correlations between urinary IgG levels and age, disease duration, serum creatinine, A/C ratio, and urea. Positive correlation between serum fractalkine CX3CL1 level and age, duration of disease, urea, creatinine, A/C ratio, HbA1C and IgG in patient with DN. Serum CX3CL1 level, urinary IgG were significantly increased with the progress of nephropathy so these integrated biomarkers could be used as good predictors for early identification of nephropathy. But miRNA- 152-3p has inadequate prognostic indicator for ESRD progression.
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Affiliation(s)
- Aml E Abdou
- Microbiology and Immunology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Haneya A A Anani
- Microbiology and Immunology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Hanan F Ibrahim
- Microbiology and Immunology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Eman Elshohat Ebrahem
- Biochemistry Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Nora Seliem
- Biochemistry Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Eman M I Youssef
- Biochemistry Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.,Biochemistry Department, College of Medicine, Taif University, Taif, Saudi Arabia
| | - Niveen M Ghoraba
- Clinical Pathology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Asmaa S Hassan
- Clinical Pathology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Marwa A A Ramadan
- Clinical Pathology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Eman Mahmoud
- Department of Endocrinology and Metabolism, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Shorouk Issa
- Department of Endocrinology and Metabolism, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Hend M Maghraby
- Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Eman K Abdelrahman
- Internal Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
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