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Jiang L, Li L, Zhang K, Zheng L, Zhang X, Hou Y, Cao M, Wang Y. A systematic review and meta-analysis of microRNAs in the diagnosis of early diabetic kidney disease. Front Endocrinol (Lausanne) 2025; 16:1432652. [PMID: 40331139 PMCID: PMC12052537 DOI: 10.3389/fendo.2025.1432652] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 03/28/2025] [Indexed: 05/08/2025] Open
Abstract
Objective The aim of this study was to comprehensively assess the overall diagnostic value of circulating microRNAs (miRNAs or miRs) as biomarkers for the early diagnosis of diabetic kidney disease (DKD) through Meta-analysis, and to identify potential molecular biomarkers with higher diagnostic value for early DKD. Methods The CNKI, Wanfang date, VIP, Pubmed, Embase, Web of Science, and Cochrane Library until January 2024 were searched. Relevant studies associated with the value of miRNAs in the diagnosis of early DKD were selected. Case numbers, sensitivity, and specificity were extracted from the included literature for both the observation and control groups. Results Nine studies including 655 cases of early DKD patients and 664 cases as a control group were conducted. The comprehensive sensitivity was 0.76, comprehensive specificity was 0.74, combined positive likelihood ratio was 2.9 and the combined negative likelihood ratio was 0.33, diagnostic odds ratio (DOR) was 9. The summary receiver operating characteristic (SROC) curve was drawn and the area under the curve (AUC) was 0.79. Blood and urine source data were analyzed and showed that urine source miRNA had a higher sensitivity (0.82vs 0.68) and a higher DOR (10.5vs 8.2) than blood source miRNA. Conclusion MiRNAs may serve as promising noninvasive biomarkers for the early diagnosis of DKD. The diagnostic value of miRNAs in urine samples may be higher than that in blood samples. The combined detection of some miRNAs or other clinical indicators can enhance the accuracy of early DKD diagnosis. Systematic Review Registration https://osf.io, identifier DOI: 10.17605/OSF.IO/FC6DK.
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Affiliation(s)
- Lujie Jiang
- Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
| | - Li Li
- Department of Endocrinology, The First People’s Hospital of Taian, Taian, Shandong, China
| | - Ke Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
| | - Liping Zheng
- Department of Endocrinology, The First People’s Hospital of Ningyang, Taian, Shandong, China
| | - Xinhuan Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
| | - Yanlian Hou
- Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
| | - Mingfeng Cao
- Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
| | - Yan Wang
- Department of Endocrinology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
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Liu D, Yu S, Zhang Y, Li Q, Kang P, Wang L, Han R, Cheng D, Chen A, Hou X, Wu L, Zang S, Fang Q, Jia W, Li H. Fibroblast growth factor 23 predicts incident diabetic kidney disease: A 4.6-year prospective study. Diabetes Obes Metab 2025; 27:2232-2241. [PMID: 39895483 PMCID: PMC11885106 DOI: 10.1111/dom.16224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/11/2025] [Accepted: 01/19/2025] [Indexed: 02/04/2025]
Abstract
AIMS Fibroblast growth factor (FGF) 23 is a bone-derived phosphaturic hormone that participates in the regulation of mineral metabolism and the development of chronic kidney disease. This study aimed to investigate the association between FGF23 and diabetic kidney disease (DKD) in a community-based prospective cohort. MATERIALS AND METHODS Of 7230 individuals who completed a 4.6-year follow-up survey, 1614 individuals with diabetes at baseline were included in this study. Baseline serum FGF23 levels were measured by enzyme-linked immunosorbent assay. Multiple and ordinal logistic regression analyses were used to examine the predictive performance of baseline FGF23 for incident DKD. RESULTS Baseline serum FGF23 levels exhibited an earlier elevation in the course of DKD and a gradual increase with the progressive stages of DKD (p < 0.05), while no statistical changes were observed in serum calcium and phosphorus levels. Over a 4.6-year follow-up, 198 individuals with diabetes developed incident DKD. Baseline FGF23 was significantly associated with the incidence of DKD (odds ratio 1.290 [95% CI 1.063, 1.565]) after adjusting for conventional DKD risk factors, especially in individuals with lower body mass index (<24 kg/m2), worse glycaemic control (HbA1c ≥7%), and shorter duration of diabetes (<5 years). Moreover, FGF23 models exhibited great performances in DKD risk prediction and yielded increments compared to traditional DKD risk factors (p < 0.05). CONCLUSIONS Serum FGF23 level increased at early stages of DKD, and it was an independent predictor of incident DKD, suggesting its potential for early identification of individuals at risk.
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Affiliation(s)
- Dan Liu
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Shujie Yu
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Ying Zhang
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Qian Li
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
| | - Piao Kang
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Lihong Wang
- Department of Endocrinology, Shanghai Fifth People's HospitalFudan UniversityShanghaiChina
| | - Rui Han
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Di Cheng
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Anran Chen
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
- Department of MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Xuhong Hou
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
| | - Liang Wu
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
| | - Shufei Zang
- Department of Endocrinology, Shanghai Fifth People's HospitalFudan UniversityShanghaiChina
| | - Qichen Fang
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
| | - Weiping Jia
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
| | - Huating Li
- Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Institute for Proactive HealthcareShanghai Jiao Tong UniversityShanghaiChina
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Fan Z, Wei X, Zhu X, Du Y. Sirtuins in kidney homeostasis and disease: where are we now? Front Endocrinol (Lausanne) 2025; 15:1524674. [PMID: 39911234 PMCID: PMC11794115 DOI: 10.3389/fendo.2024.1524674] [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: 11/08/2024] [Accepted: 12/31/2024] [Indexed: 02/07/2025] Open
Abstract
Sirtuins, identified as (NAD+)- dependent class III histone deacetylases, engage in a spectrum of biological functions, encompassing DNA damage repair, oxidative stress, immune modulation, mitochondrial homeostasis, apoptosis and autophagy. Sirtuins play an apoptosis role in regulating cellular operations and overall organism health. Mounting data indicate that dysregulated sirtuin expression is linked to the onset of renal diseases. Effective modulation of sirtuins expression and activity has been shown to improve renal function and attenuate the advancement of kidney diseases. In this review, we present a comprehensive overview of the biological impacts of sirtuins and their molecular targets in regulating renal diseases. Additionally, we detail advancements in elucidating sirtuin roles in the pathophysiology of both chronic and acute renal disorders. We review compounds that modulate sirtuin activity through activation or inhibition, potentially improving outcomes in renal disease. In summary, strategic manipulation of sirtuin activity represents a prospective therapeutic approach for renal diseases.
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Affiliation(s)
| | | | | | - Yujun Du
- Department of Nephrology, The First Hospital of Jilin University, Changchun, China
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Wang XR, Wu Z, He TT, Chen XH, Jin XF, Zuo CY, Yang SZ, Gao Y, Zhou XH, Gao WJ. Global research hotspots and trends in oxidative stress-related diabetic nephropathy: a bibliometric study. Front Endocrinol (Lausanne) 2025; 15:1451954. [PMID: 39866738 PMCID: PMC11757133 DOI: 10.3389/fendo.2024.1451954] [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: 06/20/2024] [Accepted: 12/19/2024] [Indexed: 01/28/2025] Open
Abstract
Background Oxidative stress is widely acknowledged as a key pathogenic mechanism in diabetic nephropathy (DN). In recent years, the role of oxidative stress in DN has garnered increasing attention. However, no bibliometric analysis has yet been conducted on the relationship between oxidative stress and DN. This study aims to systematically analyze the relevant literature, identify trends in research, assess current hotspots, and predict future directions. Methods We retrieved literature related to oxidative stress and DN from the Web of Science Core Collection database. We analyzed data on publication volume, countries/regions, institutions, journals, keywords, and other relevant metrics using VOSviewer, the Bibliometrix R package, and CiteSpace. Results From 2014 to 2024, a total of 4076 publications related to oxidative stress and DN were published across 755 journals, showing a consistent upward trend each year. China and the United States are the leading contributors in this field and demonstrate close collaborative efforts. The top contributors by country, institution, journal, and author include: China (1919 publications), Jilin University and Central South University (69 publications each), BIOMEDICINE & PHARMACOTHERAPY (117 publications), and Prof. Sun Lin (33 publications). The most frequent keyword is "oxidative stress" (3683 occurrences). In the co-citation analysis, Alicic RZ's 2017 study was the most cited (144 citations). These findings highlight the critical importance of investigating the pathogenesis of DN from the oxidative stress perspective. Conclusion This study demonstrates a steady increase in research on oxidative stress in DN since 2014, highlighting its central role in the pathogenesis of DN. Future research should focus on the molecular mechanisms of oxidative stress in DN and explore its therapeutic potential, to provide new strategies for the prevention and treatment of DN.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiao-hong Zhou
- Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Wei-juan Gao
- Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Hebei University of Chinese Medicine, Shijiazhuang, China
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Lu Q, Hu X, Hou Q, Yu L, Cao K, Ding D, Lu Y, Dai C. Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation. Cell Signal 2024; 124:111451. [PMID: 39389178 DOI: 10.1016/j.cellsig.2024.111451] [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: 06/30/2024] [Revised: 09/19/2024] [Accepted: 09/30/2024] [Indexed: 10/12/2024]
Abstract
Podocyte senescence can cause persistent podocyte injury and albuminuria in diabetic kidney disease (DKD), but the mechanism remains obscure. In this study, podocyte senescence was confirmed by immunohistochemical staining in podocytes from patients and mice with DKD. Rheb1 knockout in podocytes aggravated podocyte senescence and injury in diabetic mice, but mitigated podocyte injury in mice with podocyte-specific mTORC1 activation induced by Tsc1 deletion. In cultured podocytes, Rheb1 knockdown remarkably accelerated podocyte senescence, independent of mTORC1. Mechanistically, PDH phosphorylation in podocyte was correlated with podocyte senescence in DKD patients. Rheb1 deficiency decreased ATP, mitochondrial membrane potential and partial components of respiratory chain complex, and enhanced ROS production and PDH phosphorylation, which indicates mitochondrial dysfunction, both in vitro and in vivo. Furthermore, Rheb1 interacted with Atp5f1c, and regulated its acetylation under a high-glucose condition. Together, Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation, in an mTORC1-independent manner, which provides experimental basis for the treatment of DKD.
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Affiliation(s)
- Qingmiao Lu
- Department of Endocrinology, 2(nd) Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan, Nanjing, Jiangsu, China
| | - Xiao Hu
- Department of Endocrinology, 2(nd) Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan, Nanjing, Jiangsu, China; Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, No. 666 Shengli Road, Nantong 226001, China
| | - Qing Hou
- Center for Kidney Disease, 2(nd) Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China
| | - Long Yu
- Center for Kidney Disease, 2(nd) Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China
| | - Kai Cao
- Center for Kidney Disease, 2(nd) Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China
| | - Dafa Ding
- Department of Endocrinology, 2(nd) Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan, Nanjing, Jiangsu, China
| | - Yibing Lu
- Department of Endocrinology, 2(nd) Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan, Nanjing, Jiangsu, China.
| | - Chunsun Dai
- Center for Kidney Disease, 2(nd) Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China; Department of Clinical Genetics, 2(nd) Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
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Ren H, Shao Y, Ma X, An L, Liu Y, Wang Q. Interaction of circulating TGFβ regulatory miRNAs in different severity of diabetic kidney disease. Arch Physiol Biochem 2024; 130:285-299. [PMID: 35147479 DOI: 10.1080/13813455.2022.2034884] [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: 11/02/2021] [Revised: 12/21/2021] [Accepted: 01/20/2022] [Indexed: 11/02/2022]
Abstract
AIMS To explore the interaction of TGFβ regulatory microRNAs (miRNAs) with different severities of diabetic kidney disease (DKD). METHODS According to different UACR (30 and 300 mg/g), 436 subjects were included, and high glucose induced RMCs were cultured. Real-time PCR, ELISA, and automatic biochemical analysis were used to measure miRNAs, TGFβ1, and other biochemical indicators in serum and RMCs. Target genes of miRNA were predicted and visualised by bioinformatics. RESULTS HbA1c, TGFβ1, miR-217, and miR-224 in T2DM patients increased with UACR, while miR-192 and miR-216a decreased. Ln UACR was positively correlated with HbA1c, TGFβ1, miR-217, and miR-224, and negatively correlated with miR-192 and miR-216a. High glucose and TGFβ1 affected miRNAs and these miRNAs affected each other. The miRNA target genes mainly revolve around PTEN, PI3K/Akt, and MAPK signalling pathways. CONCLUSION TGFβ regulatory miRNAs and different severity of DKD have a potential interaction regulating fibrosis through PTEN, PI3K/Akt, and MAPK pathways.
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Affiliation(s)
- Huiwen Ren
- Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Ying Shao
- Department of Endocrinology, The Second Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiaoyu Ma
- The Cadre Department, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Li An
- Department of Gastroenterology, Tieling Central Hospital, Tieling, Liaoning, China
| | - Yu Liu
- Department of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qiuyue Wang
- Department of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
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Fukata F, Eriguchi M, Tamaki H, Uemura T, Tasaki H, Furuyama R, Nishimoto M, Kosugi T, Tanabe K, Morimoto K, Okamoto K, Matsui M, Samejima KI, Tsuruya K. Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy. Clin Exp Nephrol 2024; 28:282-292. [PMID: 38019364 DOI: 10.1007/s10157-023-02433-y] [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: 09/02/2023] [Accepted: 10/31/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Studies on kidney function and histological findings in diabetic nephropathy (DN) with low urinary protein (UP) are few. We examined the differential impact of histological changes on kidney outcomes between non-proteinuric and proteinuric DN. METHODS Patients diagnosed with DN by renal biopsy during 1981-2014 were divided into non-proteinuric (UP ≤ 0.5 g/day) and proteinuric (UP > 0.5 g/day) DN. The Cox proportional hazard model was used to examine the association of glomerular lesions (GLs) and interstitial fibrosis and tubular atrophy (IFTA) with end-stage kidney disease (ESKD) development after adjusting for relevant confounders. RESULTS The non-proteinuric and proteinuric DN groups included 197 and 199 patients, respectively. During the 10.7-year median follow-up period, 16 and 83 patients developed ESKD in the non-proteinuric and proteinuric DN groups, respectively. In the multivariable Cox hazard model, hazard ratios (HRs) [95% confidence intervals (CIs)] of GL and IFTA for ESKD in proteinuric DN were 2.94 [1.67-5.36] and 3.82 [2.06-7.53], respectively. Meanwhile, HRs [95% CIs] of GL and IFTA in non-proteinuric DN were < 0.01 [0-2.48] and 4.98 [1.33-18.0], respectively. IFTA was consistently associated with higher incidences of ESKD regardless of proteinuria levels (P for interaction = 0.49). The prognostic impact of GLs on ESKD was significantly decreased as proteinuria levels decreased (P for interaction < 0.01). CONCLUSIONS IFTA is consistently a useful predictor of kidney prognosis in both non-proteinuric and proteinuric DN, while GLs are a significant predictor of kidney prognosis only in proteinuric DN.
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Affiliation(s)
- Fumihiro Fukata
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Masahiro Eriguchi
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
| | - Hiroyuki Tamaki
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Takayuki Uemura
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Hikari Tasaki
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Riri Furuyama
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Masatoshi Nishimoto
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Takaaki Kosugi
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Kaori Tanabe
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Katsuhiko Morimoto
- Department of Nephrology, Nara Prefecture Seiwa Medical Center, Nara, Japan
| | - Keisuke Okamoto
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Masaru Matsui
- Department of Nephrology, Nara Prefecture General Medical Center, Nara, Japan
| | - Ken-Ichi Samejima
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Kazuhiko Tsuruya
- Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
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Wang K, Liu T, Zhang Y, Lv H, Yao H, Zhao Y, Li J, Li X. Combined Placental Mesenchymal Stem Cells with Guided Nanoparticles Effective Against Diabetic Nephropathy in Mouse Model. Int J Nanomedicine 2024; 19:901-915. [PMID: 38293609 PMCID: PMC10826715 DOI: 10.2147/ijn.s446733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 01/13/2024] [Indexed: 02/01/2024] Open
Abstract
Background Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs' homing to target tissues is therefore vital for the success of cell therapies in treating DN. Methods We developed Fe3O4 coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field. Results Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure. Conclusion These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.
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Affiliation(s)
- Ke Wang
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
- Gynecology and Obstetrics Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Te Liu
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Yucheng Zhang
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Huiying Lv
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Hua Yao
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Ye Zhao
- Dermatological Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Jing Li
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
| | - Xiuying Li
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
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Ravender R, Roumelioti ME, Schmidt DW, Unruh ML, Argyropoulos C. Chronic Kidney Disease in the Older Adult Patient with Diabetes. J Clin Med 2024; 13:348. [PMID: 38256482 PMCID: PMC10816477 DOI: 10.3390/jcm13020348] [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: 10/06/2023] [Revised: 12/27/2023] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and older adult individuals. DM may accelerate the aging process, and the age-related declines in the estimated glomerular filtration rate (eGFR) can pose a challenge to diagnosing diabetic kidney disease (DKD) using standard diagnostic criteria especially with the absence of severe albuminuria among older adults. In the presence of CKD and DM, older adult patients may need multidisciplinary care due to susceptibility to various health issues, e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to older adults. We review the evidence that the benefits from these newer therapies apply equally to older and younger patients with CKD and diabetes type 2 and propose a comprehensive management. This framework will address nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), sodium glucose co-transporter 2 inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and glucagon like peptide 1 receptor agonists (GLP1-RAs).
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Affiliation(s)
| | | | | | | | - Christos Argyropoulos
- Division of Nephrology, Department of Internal Medicine, University of New Mexico School of Medicine, MSC 04-2785, Albuquerque, NM 87131, USA; (R.R.); (M.-E.R.); (D.W.S.); (M.L.U.)
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10
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Kung VL, Giannini G, Nast CC. Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus before and after Availability of Direct-Acting Antiviral Therapy. GLOMERULAR DISEASES 2024; 4:74-83. [PMID: 38623264 PMCID: PMC11018331 DOI: 10.1159/000537977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 02/19/2024] [Indexed: 04/17/2024]
Abstract
Introduction Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ2 and Fisher's exact tests. Results The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, p = 0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) versus pre-DAA (1.3%) (p < 0.0001). Post-DAA there were less MPGN (2% vs. 10%, p = 0.02) and more advanced DGS (85% vs. 61%, p = 0.0002), non-collapsing FSGS (57% vs. 31%, p < 0.0001), IFTA (2.0 vs. 1.6, p = 0.0002), and vascular sclerosis (2.1 vs. 1.6, p < 0.0001). Conclusion Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.
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Affiliation(s)
- Vanderlene L Kung
- Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Gabriel Giannini
- Department of Pathology, Yosemite Pathology Medical Group, Modesto, CA, USA
| | - Cynthia C Nast
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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11
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Scurt FG, Ganz MJ, Herzog C, Bose K, Mertens PR, Chatzikyrkou C. Association of metabolic syndrome and chronic kidney disease. Obes Rev 2024; 25:e13649. [PMID: 37783465 DOI: 10.1111/obr.13649] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 09/15/2023] [Indexed: 10/04/2023]
Abstract
The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists, a significant risk of progression to end-stage renal disease remains in the high-risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin-to-creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS-associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity-related kidney injury; (ii) the clinicopathological characteristics of obesity-related kidney injury, primarily focusing on obesity-associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.
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Affiliation(s)
- Florian G Scurt
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
| | - Maximilian J Ganz
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
| | - Carolin Herzog
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
| | - Katrin Bose
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Peter R Mertens
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
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12
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Bermejo S, González E, López-Revuelta K, Ibernon M, López D, Martín-Gómez A, Garcia-Osuna R, Linares T, Díaz M, Martín N, Barros X, Marco H, Navarro MI, Esparza N, Elias S, Coloma A, Robles NR, Agraz I, Poch E, Rodas L, Lozano V, Fernández-Fernández B, Hernández E, Martínez MI, Stanescu RI, Moirón JP, García-Fernández N, Goicoechea M, Calero F, Bonet J, Liaño F, Pascual J, Bestard O, Praga M, Fulladosa X, Soler MJ. The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes. Clin Kidney J 2023; 16:1656-1663. [PMID: 37779839 PMCID: PMC10539224 DOI: 10.1093/ckj/sfad142] [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: 12/19/2022] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. METHODS We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. RESULTS Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. CONCLUSIONS DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.
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Affiliation(s)
- Sheila Bermejo
- Nephrology Department, Hospital Vall d'Hebron, Barcelona, Spain
- Vall d’Hebron Research Institute, Barcelona, Spain
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | - Ester González
- Nephrology Department, Hospital 12 de Octubre, Madrid, Spain
| | | | - Meritxell Ibernon
- Nephrology Department, Hospital Sant Joan Despí Moisès Broggi, Barcelona, Spain
| | - Diana López
- Nephrology Department, Clínica Universidad de Navarra, Pamplona, Spain
| | | | | | - Tania Linares
- Nephrology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | | | - Nàdia Martín
- Nephrology Department, Hospital Universitari Josep Trueta, Girona, Spain
| | - Xoana Barros
- Nephrology Department, Hospital Universitari Josep Trueta, Girona, Spain
| | - Helena Marco
- Nephrology Department, Fundació Puigvert, Barcelona, Spain
- Nephrology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | | | - Noemí Esparza
- Nephrology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain
| | - Sandra Elias
- Nephrology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Ana Coloma
- Nephrology Department, Hospital San Pedro, Logroño, Spain
- Nephrology Department, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | | | - Irene Agraz
- Nephrology Department, Hospital Vall d'Hebron, Barcelona, Spain
- Vall d’Hebron Research Institute, Barcelona, Spain
| | - Esteban Poch
- Nephrology Department, Hospital Clínic, Barcelona, Spain
- IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | - Lida Rodas
- Nephrology Department, Hospital Clínic, Barcelona, Spain
- IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | - Víctor Lozano
- Nephrology Department, Hospital Clínic, Barcelona, Spain
- IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | | | | | | | | | | | | | - Marian Goicoechea
- Nephrology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | | | - Josep Bonet
- Nephrology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Fernando Liaño
- Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | - Oriol Bestard
- Nephrology Department, Hospital Vall d'Hebron, Barcelona, Spain
- Vall d’Hebron Research Institute, Barcelona, Spain
| | - Manuel Praga
- Nephrology Department, Hospital 12 de Octubre, Madrid, Spain
| | - Xavier Fulladosa
- Nephrology Department, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | - María José Soler
- Nephrology Department, Hospital Vall d'Hebron, Barcelona, Spain
- Vall d’Hebron Research Institute, Barcelona, Spain
- Nephrology Department, Hospital del Mar, Barcelona, Spain
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13
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Ganz MJ, Bose K, Herzog C, Bender S, Mertens PR, Scurt FG. Pathomechanismen der chronischen Nierenschädigung bei Diabetes und anderen Begleiterkrankungen. DIE DIABETOLOGIE 2023; 19:251-261. [DOI: 10.1007/s11428-023-01020-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/15/2023] [Indexed: 01/03/2025]
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Chen HH, Zhang YX, Lv JL, Liu YY, Guo JY, Zhao L, Nan YX, Wu QJ, Zhao YH. Role of sirtuins in metabolic disease-related renal injury. Biomed Pharmacother 2023; 161:114417. [PMID: 36812714 DOI: 10.1016/j.biopha.2023.114417] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 02/08/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Poor control of metabolic diseases induces kidney injury, resulting in microalbuminuria, renal insufficiency and, ultimately, chronic kidney disease. The potential pathogenetic mechanisms of renal injury caused by metabolic diseases remain unclear. Tubular cells and podocytes of the kidney show high expression of histone deacetylases known as sirtuins (SIRT1-7). Available evidence has shown that SIRTs participate in pathogenic processes of renal disorders caused by metabolic diseases. The present review addresses the regulatory roles of SIRTs and their implications for the initiation and development of kidney damage due to metabolic diseases. SIRTs are commonly dysregulated in renal disorders induced by metabolic diseases such as hypertensive nephropathy and diabetic nephropathy. This dysregulation is associated with disease progression. Previous literature has also suggested that abnormal expression of SIRTs affects cellular biology, such as oxidative stress, metabolism, inflammation, and apoptosis of renal cells, resulting in the promotion of invasive diseases. This literature reviews the research progress made in understanding the roles of dysregulated SIRTs in the pathogenesis of metabolic disease-related kidney disorders and describes the potential of SIRTs serve as biomarkers for early screening and diagnosis of these diseases and as therapeutic targets for their treatment.
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Affiliation(s)
- Huan-Huan Chen
- Department of Oncology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Yi-Xiao Zhang
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Urology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Jia-Le Lv
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Yu-Yang Liu
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Jing-Yi Guo
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Lu Zhao
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Yu-Xin Nan
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Qi-Jun Wu
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
| | - Yu-Hong Zhao
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Clinical Research Center, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China.
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15
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Nakade Y, Iwata Y, Sakai N, Mita M, Nakane M, Hamase K, Suda W, Toyama T, Kitajima S, Hara A, Shimizu M, Ogushi C, Furuichi K, Koshino Y, Morita H, Hattori M, Wada T. Increased levels of oral Streptococcus-derived D-alanine in patients with chronic kidney disease and diabetes mellitus. Sci Rep 2022; 12:21773. [PMID: 36526888 PMCID: PMC9758232 DOI: 10.1038/s41598-022-26175-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
The number of patients on hemodialysis is increasing globally; diabetes mellitus (DM) complications is the major cause of hemodialysis in patients with chronic kidney disease (CKD). The D-amino acid (AA) profile is altered in patients with CKD; however, it has not been studied in patients with CKD and DM. Furthermore, bacteria responsible for altering the D-AA profile are not well understood. Therefore, we examined the D-AA profiles and associated bacteria in patients with CKD, with and without DM. We enrolled 12 healthy controls and 54 patients with CKD, with and without DM, and determined their salivary, stool, plasma, and urine chiral AA levels using two-dimensional high-performance liquid chromatography. We performed 16S rRNA gene sequencing analysis of the oral and gut microbiota to determine the association between the abundance of bacterial species and D-AA levels. Plasma D-alanine and D-serine levels were higher in patients with CKD than in healthy adults (p < 0.01), and plasma D-alanine levels were higher in patients with CKD and DM than in those without DM. The abundance of salivary Streptococcus, which produced D-alanine, increased in patients with CKD and DM and was positively correlated with plasma D-alanine levels. Patients with CKD and DM had unique oral microbiota and D-alanine profiles. Plasma D-alanine is a potential biomarker for patients with CKD and DM.
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Affiliation(s)
- Yusuke Nakade
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ,grid.9707.90000 0001 2308 3329Department of Clinical Laboratory, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Yasunori Iwata
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ,grid.9707.90000 0001 2308 3329Division of Infection Control, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Norihiko Sakai
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ,grid.9707.90000 0001 2308 3329Division of Blood Purification, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Masashi Mita
- grid.511730.1KAGAMI Co., Ltd., 7-18 Saitobaiohiruzu Center 308, Ibaragi, Osaka Japan
| | - Maiko Nakane
- grid.511730.1KAGAMI Co., Ltd., 7-18 Saitobaiohiruzu Center 308, Ibaragi, Osaka Japan
| | - Kenji Hamase
- grid.177174.30000 0001 2242 4849Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
| | - Wataru Suda
- grid.509459.40000 0004 0472 0267RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa Japan ,grid.26999.3d0000 0001 2151 536XGraduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba Japan
| | - Tadashi Toyama
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Shinji Kitajima
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Akinori Hara
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Miho Shimizu
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Chikako Ogushi
- grid.9707.90000 0001 2308 3329Department of Clinical Laboratory, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Kengo Furuichi
- grid.411998.c0000 0001 0265 5359Department of Nephrology, Kanazawa Medical University, 1-1 Uchinada, Kahoku, Ishikawa Japan
| | - Yoshitaka Koshino
- Department of Internal Medicine, Mizuho Hospital, 422-1 Tsubata, Kahoku, Ishikawa Japan
| | - Hidetoshi Morita
- grid.261356.50000 0001 1302 4472Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-naka, Okayama, Japan
| | - Masahira Hattori
- grid.509459.40000 0004 0472 0267RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa Japan ,grid.26999.3d0000 0001 2151 536XGraduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba Japan
| | - Takashi Wada
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
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High Prevalence of Primary Aldosteronism in Patients with Type 2 Diabetes Mellitus and Hypertension. Biomedicines 2022; 10:biomedicines10092308. [PMID: 36140406 PMCID: PMC9496555 DOI: 10.3390/biomedicines10092308] [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: 06/29/2022] [Revised: 09/06/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The prevalence of hypertension is higher in patients with diabetes mellitus-2 (DM-2). Following the limited existing data, we prospectively investigated the prevalence of aldosterone excess either as autonomous secretion (PA) or as a hyper-response to stress in hypertensive patients with DM-2 (HDM-2). A total of 137 HDM-2 patients and 61 non-diabetics with essential hypertension who served as controls (EH-C) underwent a combined, overnight diagnostic test, the Dexamethasone–captopril–valsartan test (DCVT) used for the diagnosis of PA and an ultralow dose (0.3 μg) ACTH stimulation test to identify an exaggerated aldosterone response to ACTH stimulation. Twenty-three normotensive individuals served as controls (NC) to define the normal response of aldosterone (ALD) and aldosterone-to-renin ratio (ARR) to the ultralow dose ACTH test. Using post-DCVTALD and ARR from the EH-C, and post-ACTH peak ALD and ARR from the NC, 47 (34.3%) HDM-2 patients were found to have PA, whereas 6 (10.4%) HDM-2 patients without PA (DCVT-negative) exhibited an exaggerated aldosterone response to stress—a prevalence much higher than ever reported. Treatment with mineralocorticoid receptor antagonists (MRAs) induced a significant and permanent reduction of BP in all HDM-2 patients. Early diagnosis and targeted treatment of PA is crucial to prevent any aggravating effect on chronic diabetic complications.
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17
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Ganz MJ, Bender ST, Gross C, Bose K, Mertens PR, Scurt FG. Metabolisches Syndrom und Nierenkrankheiten. DIE NEPHROLOGIE 2022; 17:291-303. [DOI: 10.1007/s11560-022-00595-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/07/2022] [Indexed: 01/04/2025]
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Advancements in nanomedicines for the detection and treatment of diabetic kidney disease. BIOMATERIALS AND BIOSYSTEMS 2022; 6:100047. [PMID: 36824160 PMCID: PMC9934479 DOI: 10.1016/j.bbiosy.2022.100047] [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] [Received: 12/22/2021] [Revised: 03/22/2022] [Accepted: 03/27/2022] [Indexed: 12/18/2022] Open
Abstract
In the diabetic kidneys, morbidities such as accelerated ageing, hypertension and hyperglycaemia create a pro-inflammatory microenvironment characterised by extensive fibrogenesis. Radiological techniques are not yet optimised generating inconsistent and non-reproducible data. The gold standard procedure to assess renal fibrosis is kidney biopsy, followed by histopathological assessment. However, this method is risky, invasive, subjective and examines less than 0.01% of kidney tissue resulting in diagnostic errors. As such, less than 10% of patients undergo kidney biopsy, limiting the accuracy of the current diabetic kidney disease (DKD) staging method. Standard treatments suppress the renin-angiotensin system to control hypertension and use of pharmaceuticals aimed at controlling diabetes have shown promise but can cause hypoglycaemia, diuresis and malnutrition as a result of low caloric intake. New approaches to both diagnosis and treatment are required. Nanoparticles (NPs) are an attractive candidate for managing DKD due to their ability to act as theranostic tools that can carry drugs and enhance image contrast. NP-based point-of-care systems can provide physiological information previously considered unattainable and provide control over the rate and location of drug release. Here we discuss the use of nanotechnology in renal disease, its application to both the treatment and diagnosis of DKD. Finally, we propose a new method of NP-based DKD classification that overcomes the current systems limitations.
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miR-154-5p Affects the TGFβ1/Smad3 Pathway on the Fibrosis of Diabetic Kidney Disease via Binding E3 Ubiquitin Ligase Smurf1. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:7502632. [PMID: 35126820 PMCID: PMC8814716 DOI: 10.1155/2022/7502632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 12/20/2021] [Accepted: 01/03/2022] [Indexed: 11/29/2022]
Abstract
Aim The study is aimed at verifying miR-154-5p and Smurf1 combination in glomerular mesangial cells regulating TGFβ1/Smad3 pathway-related protein ubiquitination in the model of diabetic rats renal tissues, primary mesangial cells, and cell lines. Methods The diabetic SD rat model and high-glucose-cultured primary mesangial cells and cell lines were established. miR-154-5p mimic and inhibitor, Smurf1 siRNA, and TGF β 1/Smad3 inhibitor (SB431542) were pretreated to make the TGFβ1/Smad3 pathway and ubiquitin changes. Fluorescence in situ hybridization was used for the miR-154-5p renal localization; molecular biological detection was adopted for cell proliferation, renal function, urine protein, and pathway proteins. After bioinformatics predicted binding sites, luciferase and Co-IP were used to detect miRNA and protein binding. Results miR-154-5p was significantly increased and mainly concentrated in the glomerular of renal cortex in well-established diabetic rat renal tissues. Rno-miR-154-5p combined Rno-Smurf1 3′ UTR, while Smurf1 combined Smad3 directly. Meanwhile, miR-154-5p regulates TGFβ1/Smad3-mediated cell proliferation via Smurf1 ubiquitination. Conclusion miR-154-5p regulates the TGFβ1/Smads pathway through Smurf1 ubiquitination and promotes the fibrosis process of diabetic kidney disease.
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An L, Yu Q, Chen L, Tang H, Liu Y, Yuan Q, Ji Y, Lee Y, Lu J. The Association Between the Decline of eGFR and a Reduction of Hemoglobin A 1c in Type 2 Diabetic Patients. Front Endocrinol (Lausanne) 2022; 12:723720. [PMID: 35126306 PMCID: PMC8807519 DOI: 10.3389/fendo.2021.723720] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 12/09/2021] [Indexed: 11/24/2022] Open
Abstract
Objective This study aimed to explore the relationship between short-term (≤12 months) changes in the estimated glomerular filtration rate (eGFR) and hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D). Method A total of 2,599 patients with T2D were enrolled if they were registered in the Diabetes Sharecare Information System, were aged 18-75 years, and had 2-3 HbA1c and eGFR measurements within the preceding 12 months. The studied patients were categorized into five groups based on eGFR, i.e., the relatively stable (RS), fast decline (FD), modest decline (MD), modest increase (MI), and fast increase (FI) groups. Results The median eGFR changes from baseline were -22.14, -6.44, 0.00, 6.32, and 20.00 ml/min per 1.73 m2 for patients in the FD, MD, RS, MI, and FI groups, respectively. Up to 1,153 (44.4%) subjects experienced an eGFR decline of ≥3.5 ml/min per 1.73 m2, including 821 (31.6%) FD subjects and 332 (12.8%) MD subjects. A decreased trend was found between the eGFR change and HbA1c decrease category, even after multivariable adjustment. In general, an eGFR FD was frequently found in patients who had an HbA1c reduction of ≥3.00% and a baseline HbA1c ≥8.0%; alternatively, such a result was also observed for a urinary albumin-to-creatinine ratio (UACR) of 30.0-300.0 mg/g, regardless of a diabetes duration of <10.0 or ≥10.0 years, or in patients who had an HbA1c reduction of ≥1.00% accompanied by hyperfiltration. Conclusions Some patients with T2D experienced an eGFR FD or MD during the ≤12-month follow-up period. A significant downward trend in eGFR change was demonstrated alongside an HbA1c reduction, independent of UACR stage, diabetes duration, and hyperfiltration. Sustained monitoring and cautious interpretation of the HbA1c and eGFR changes will be needed in clinical practice.
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Affiliation(s)
- Lingwang An
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
| | - Qiuzhi Yu
- Department of Endocrinology, Heilongjiang Ruijing Diabetes Hospital, Haerbin, China
| | - Linhui Chen
- Department of Endocrinology, Taiyuan Diabetes Hospital, Taiyuan, China
| | - Hong Tang
- Department of Share-care Center, Chengdu Ruien Diabetes Hospital, Chengdu, China
| | - Yanjun Liu
- Department of Endocrinology, Lanzhou Ruijing Diabetes Hospital, Lanzhou, China
| | - Qun Yuan
- Department of Endocrinology, Heilongjiang Ruijing Diabetes Hospital, Haerbin, China
| | - Yu Ji
- Department of Endocrinology, Beijing Aerospace General Hospital, Beijing, China
| | | | - Juming Lu
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
- Department of Endocrinology, The General Hospital of the People’s Liberation Army, Beijing, China
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21
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Pan Y, Liu L, Yang H, Chen W, Chen Z, Xu J. Sacubitril/Valsartan Improves Progression of Early Diabetic Nephropathy in Rats Through Inhibition of NLRP3 Inflammasome Pathway. Diabetes Metab Syndr Obes 2022; 15:2479-2488. [PMID: 35992034 PMCID: PMC9386175 DOI: 10.2147/dmso.s366518] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 08/02/2022] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Diabetic nephropathy (DN), a global disease, is the leading cause of end-stage renal disease. There is a lack of specific treatment for this disease, and early intervention in disease progression is essential. In this paper, we used a rat model of early diabetic nephropathy to explore the therapeutic mechanism of sacubitril/valsartan in rats with early diabetic nephropathy. MATERIALS AND METHODS Rats were grouped into 1 normal group; 2. Model group (DN group): STZ (45 mg/kg/d) induced early diabetic nephropathy rats; 3. Sac group: DN rats + Sac group (orally, 60 mg/kg/d) for 6 weeks. After 6 weeks, the levels of serum albumin (ALB), glucose (GLU), creatinine (Cr), urea nitrogen (BUN) and 24-h urinary protein excretion were measured. In renal tissue homogenates, NLRP3 inflammasome, proinflammatory factors IL1-β and TNF-α, oxidative stress MDA and pro-fibrotic cytokine TGF-β1 were performed. Histological analysis of kidneys by hematoxylin and eosin (HE), PAS and Masson trichrome staining. RESULTS 1. Sacubitril/valsartan (Sac) significantly improved renal hypertrophy, proteinuria and serum albumin levels in rats with early diabetic nephropathy (P < 0.001), and decreased GLU, Scr (P<0.001), and BUN levels (P < 0.01).2. Light microscopy of renal tissues showed glomerular hypertrophy and interstitial inflammatory cell infiltration, and mean glomerular area (MGA) and mean glomerular volume (MGV) were crucially increased in early diabetic nephropathy (P < 0.001), and the Sac group showed reduced renal pathology and improved MGA and MGV (P < 0.001).3. Kidney tissue homogenate levels of NLRP3, Caspase-1, IL1-β, TNF-α, MDA and TGF-β1 were critically, increased in DN rats (P < 0.001), and SOD was significantly decreased. All these indicators above were improved after treatment (P < 0.0001). CONCLUSION Nlrp3-inflammasome promote progression of diabetic nephropathy through inflammation, fibrosis and oxidative stress; sacubitril/valsartan ameliorated early diabetes-induced renal damage by inhibiting NLRP3 pathway activation.
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Affiliation(s)
- Yan Pan
- Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China
- Correspondence: Yan Pan, Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Longzihu District, Bengbu City, Anhui Province, 233000, People’s Republic of China, Tel +86 13865030612, Email
| | - Lei Liu
- Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China
| | - Huijuan Yang
- Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China
| | - Weidong Chen
- Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China
| | - Zheng Chen
- Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China
| | - Jing Xu
- Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu City, People’s Republic of China
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22
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Zhang W, Liu X, Dong Z, Wang Q, Pei Z, Chen Y, Zheng Y, Wang Y, Chen P, Feng Z, Sun X, Cai G, Chen X. New Diagnostic Model for the Differentiation of Diabetic Nephropathy From Non-Diabetic Nephropathy in Chinese Patients. Front Endocrinol (Lausanne) 2022; 13:913021. [PMID: 35846333 PMCID: PMC9279696 DOI: 10.3389/fendo.2022.913021] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/20/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The disease pathology for diabetes mellitus patients with chronic kidney disease (CKD) may be diabetic nephropathy (DN), non-diabetic renal disease (NDRD), or DN combined with NDRD. Considering that the prognosis and treatment of DN and NDRD differ, their differential diagnosis is of significance. Renal pathological biopsy is the gold standard for diagnosing DN and NDRD. However, it is invasive and cannot be implemented in many patients due to contraindications. This article constructed a new noninvasive evaluation model for differentiating DN and NDRD. METHODS We retrospectively screened 1,030 patients with type 2 diabetes who has undergone kidney biopsy from January 2005 to March 2017 in a single center. Variables were ranked according to importance, and the machine learning methods (random forest, RF, and support vector machine, SVM) were then used to construct the model. The final model was validated with an external group (338 patients, April 2017-April 2019). RESULTS In total, 929 patients were assigned. Ten variables were selected for model development. The areas under the receiver operating characteristic curves (AUCROCs) for the RF and SVM methods were 0.953 and 0.947, respectively. Additionally, 329 patients were analyzed for external validation. The AUCROCs for the external validation of the RF and SVM methods were 0.920 and 0.911, respectively. CONCLUSION We successfully constructed a predictive model for DN and NDRD using machine learning methods, which were better than our regression methods. CLINICAL TRIAL REGISTRATION ClinicalTrial.gov, NCT03865914.
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Affiliation(s)
- WeiGuang Zhang
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - XiaoMin Liu
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - ZheYi Dong
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - Qian Wang
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - ZhiYong Pei
- Beijing Computing Center, Beike Industry, Yongfeng Industrial Base, Beijing, China
| | - YiZhi Chen
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
- Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, the Hainan Academician Team Innovation Center, Sanya, China
| | - Ying Zheng
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - Yong Wang
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - Pu Chen
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - Zhe Feng
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - XueFeng Sun
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
| | - Guangyan Cai
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
- *Correspondence: XiangMei Chen, ; Guangyan Cai,
| | - XiangMei Chen
- Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China
- *Correspondence: XiangMei Chen, ; Guangyan Cai,
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23
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Liu S, Gui Y, Wang MS, Zhang L, Xu T, Pan Y, Zhang K, Yu Y, Xiao L, Qiao Y, Bonin C, Hargis G, Huan T, Yu Y, Tao J, Zhang R, Kreutzer DL, Zhou Y, Tian XJ, Wang Y, Fu H, An X, Liu S, Zhou D. Serum integrative omics reveals the landscape of human diabetic kidney disease. Mol Metab 2021; 54:101367. [PMID: 34737094 PMCID: PMC8609166 DOI: 10.1016/j.molmet.2021.101367] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/16/2021] [Accepted: 10/26/2021] [Indexed: 01/02/2023] Open
Abstract
Objective Diabetic kidney disease (DKD) is the most common microvascular complication of type 2 diabetes mellitus (2-DM). Currently, urine and kidney biopsy specimens are the major clinical resources for DKD diagnosis. Our study proposes to evaluate the diagnostic value of blood in monitoring the onset of DKD and distinguishing its status in the clinic. Methods This study recruited 1,513 participants including healthy adults and patients diagnosed with 2-DM, early-stage DKD (DKD-E), and advanced-stage DKD (DKD-A) from 4 independent medical centers. One discovery and four testing cohorts were established. Sera were collected and subjected to training proteomics and large-scale metabolomics. Results Deep profiling of serum proteomes and metabolomes revealed several insights. First, the training proteomics revealed that the combination of α2-macroglobulin, cathepsin D, and CD324 could serve as a surrogate protein biomarker for monitoring DKD progression. Second, metabolomics demonstrated that galactose metabolism and glycerolipid metabolism are the major disturbed metabolic pathways in DKD, and serum metabolite glycerol-3-galactoside could be used as an independent marker to predict DKD. Third, integrating proteomics and metabolomics increased the diagnostic and predictive stability and accuracy for distinguishing DKD status. Conclusions Serum integrative omics provide stable and accurate biomarkers for early warning and diagnosis of DKD. Our study provides a rich and open-access data resource for optimizing DKD management.
Serum proteomics and metabolomics are novel, noninvasive approaches to detect DKD. Integrated serum omics enhances the diagnostic stability and accuracy of DKD diagnoses. Galactose/glycerolipid metabolism is the major disturbed metabolic pathway in DKD. Serum metabolite glycerol-3-galactoside is an independent predictive marker of DKD.
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Affiliation(s)
- Shijia Liu
- Affiliated Hosptial of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China; IIT Research Institute, Chicago, IL, USA
| | - Yuan Gui
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Mark S Wang
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Lu Zhang
- Affiliated Hosptial of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Tingting Xu
- Affiliated Hosptial of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yuchen Pan
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ke Zhang
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Renal Division, The 3rd Xiangya Hospital, Central South University, Changsha, China
| | - Ying Yu
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Renal Division, Tongji Hospital, Tongji University, Shanghai, China
| | - Liangxiang Xiao
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Renal Division, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Yi Qiao
- Department of Surgery, University of Connecticut School of Medicine, Farmington, CT, USA
| | | | - Geneva Hargis
- University of Connecticut School of Medicine, Farmington, CT, USA
| | - Tao Huan
- Department of Chemistry, University of British Columbia, Vancouver, BC, Canada
| | - Yanbao Yu
- Department of Chemistry & Biochemistry, University of Delaware, Newark, DE, USA
| | - Jianling Tao
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Rong Zhang
- School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA
| | - Donald L Kreutzer
- Department of Surgery, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Yanjiao Zhou
- University of Connecticut School of Medicine, Farmington, CT, USA
| | - Xiao-Jun Tian
- School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA
| | - Yanlin Wang
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Haiyan Fu
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaofei An
- Affiliated Hosptial of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China; Vascular Biology Center, Medical College of Georgia, Augusta University, GA, USA.
| | - Silvia Liu
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
| | - Dong Zhou
- Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
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Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study. Int J Nephrol 2021; 2021:9999621. [PMID: 34336286 PMCID: PMC8292077 DOI: 10.1155/2021/9999621] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/03/2021] [Indexed: 12/29/2022] Open
Abstract
Background Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. Methods We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. Results Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. Conclusions After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.
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Advanced Glycation End Products: New Clinical and Molecular Perspectives. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18147236. [PMID: 34299683 PMCID: PMC8306599 DOI: 10.3390/ijerph18147236] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/30/2021] [Accepted: 07/03/2021] [Indexed: 12/17/2022]
Abstract
Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.
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26
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García-Carro C, Vergara A, Bermejo S, Azancot MA, Sánchez-Fructuoso AI, Sánchez de la Nieta MD, Agraz I, Soler MJ. How to Assess Diabetic Kidney Disease Progression? From Albuminuria to GFR. J Clin Med 2021; 10:jcm10112505. [PMID: 34198818 PMCID: PMC8201333 DOI: 10.3390/jcm10112505] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetic kidney disease (DKD) is one of the most relevant complications of type 2 diabetes and dramatically increases the cardiovascular risk in these patients. Currently, DKD is severely infra-diagnosed, or its diagnosis is usually made at advanced stages of the disease. During the last decade, new drugs have demonstrated a beneficial effect in terms of cardiovascular and renal protection in type 2 diabetes, supporting the crucial role of an early DKD diagnosis to permit the use of new available therapeutic strategies. Moreover, cardiovascular and renal outcome trials, developed to study these new drugs, are based on diverse cardiovascular and renal simple and composite endpoints, which makes difficult their interpretation and the comparison between them. In this article, DKD diagnosis is reviewed, focusing on albuminuria and the recommendations for glomerular filtration rate measurement. Furthermore, cardiovascular and renal endpoints used in classical and recent cardiovascular outcome trials are assessed in a pragmatic way.
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Affiliation(s)
- Clara García-Carro
- Nephrology Department, San Carlos Clinical University Hospital, 28040 Madrid, Spain; (C.G.-C.); (A.I.S.-F.); (M.D.S.d.l.N.)
| | - Ander Vergara
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
| | - Sheila Bermejo
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
| | - María A. Azancot
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
| | - Ana I. Sánchez-Fructuoso
- Nephrology Department, San Carlos Clinical University Hospital, 28040 Madrid, Spain; (C.G.-C.); (A.I.S.-F.); (M.D.S.d.l.N.)
| | - M. Dolores Sánchez de la Nieta
- Nephrology Department, San Carlos Clinical University Hospital, 28040 Madrid, Spain; (C.G.-C.); (A.I.S.-F.); (M.D.S.d.l.N.)
| | - Irene Agraz
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
- Correspondence: (I.A.); (M.J.S.)
| | - María José Soler
- Nephrology Research Group, Nephrology Department, Vall d’Hebrón Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebrón Hospital Universitari, 08035 Barcelona, Spain; (A.V.); (S.B.); (M.A.A.)
- Correspondence: (I.A.); (M.J.S.)
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Abstract
Diabetic kidney disease (DKD) is one of the most common chronic microvascular complications of diabetes. In addition to the characteristic clinical manifestations of proteinuria, it also has a complex pathological process that results from the combined effects of multiple factors involving the whole renal structure such as glomeruli, renal tubules, and blood vessels. Non-coding RNAs (ncRNA) are transcripts with no or low coding potential, among which micro RNA (miRNA) has been widely studied as a functional miRNA involved in regulation and a potential biomarker for disease prediction. The abundance of long coding RNA (lncRNA) in vivo is highly expressed with a certain degree of research progress, but the structural similarity makes the research still challenging. The research of circular RNA (circRNA) is still in its early stages. It is more relevant to the study to provide a more relevant link between diseases in the kidney and other tissues or organs. This classification review mainly summarized the biogenesis characteristics, the pathological mechanism of ncRNA-regulating diseases, the ways of ncRNA in the clinical prediction as a potential biomarker, and the interaction networks of ncRNA.
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Affiliation(s)
- Huiwen Ren
- Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
| | - Qiuyue Wang
- Department of Endocrinology, the First Hospital Affiliated of China Medical University, Shenyang, China
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28
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Scurt FG, Bose K, Canbay A, Mertens PR, Chatzikyrkou C. [Chronic kidney injury in patients with liver diseases - Reappraising pathophysiology and treatment options]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:560-579. [PMID: 33728618 DOI: 10.1055/a-1402-1502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.
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Affiliation(s)
- Florian Gunnar Scurt
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Katrin Bose
- Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany.,Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland
| | - Ali Canbay
- Ruhr-Universität Bochum, Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland
| | - Peter R Mertens
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Christos Chatzikyrkou
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
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29
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Xiong J, Hu H, Guo R, Wang H, Jiang H. Mesenchymal Stem Cell Exosomes as a New Strategy for the Treatment of Diabetes Complications. Front Endocrinol (Lausanne) 2021; 12:646233. [PMID: 33995278 PMCID: PMC8117220 DOI: 10.3389/fendo.2021.646233] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 04/12/2021] [Indexed: 01/01/2023] Open
Abstract
Diabetes mellitus (DM) is a metabolic disease, now prevalent worldwide, which is characterized by a relative or absolute lack of insulin secretion leading to chronically increased blood glucose levels. Diabetic patients are often accompanied by multiple macrovascular complications, such as coronary heart disease, hypertension, macrovascular arteriosclerosis, and microvascular complications. Microvascular complications include diabetic kidney injury, diabetic encephalopathy, and diabetic foot, which reduce the quality of life and survival status of patients. Mesenchymal stem cell exosomes (MSC-Exos) possess repair functions similar to MSCs, low immunogenicity, and ease of storage and transport. MSC-Exos have been proven to possess excellent repair effects in repairing various organ damages. This study reviews the application of MSC-Exos in the treatment of DM and its common complications. MSC-Exos may be used as an effective treatment for DM and its complications.
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Affiliation(s)
| | | | | | - Hui Wang
- *Correspondence: Hui Wang, ; Hua Jiang,
| | - Hua Jiang
- *Correspondence: Hui Wang, ; Hua Jiang,
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30
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Di Paolo S, Fiorentino M, De Nicola L, Reboldi G, Gesualdo L, Barutta F, Natali A, Penno G, Fioretto P, Pugliese G. Indications for renal biopsy in patients with diabetes. Joint position statement of the Italian Society of Nephrology and the Italian Diabetes Society. Nutr Metab Cardiovasc Dis 2020; 30:2123-2132. [PMID: 33239162 DOI: 10.1016/j.numecd.2020.09.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/10/2020] [Indexed: 12/31/2022]
Abstract
AIMS This joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence. DATA SYNTHESIS Renal biopsy has a pivotal role in assessing the nature and severity of renal injury in patients with diabetic kidney disease (DKD). The procedure is mandatory in the presence of one of more of the following features: rapid onset or progression of albuminuria or sudden onset of nephrotic syndrome, rapid GFR decline with or without albuminuria, hematuria, active urine sediment, clinical and/or laboratory suspicion of other systemic diseases, and, in patients with type 1 diabetes, short diabetes duration and absence of retinopathy. Indeed, ~40% of diabetic individuals with kidney injury undergoing renal biopsy are affected by a non-diabetic renal disease (NDRD). Furthermore, the histological evaluation of patients with suspected classical diabetic nephropathy allows to define the extent of glomerular, tubulo-interstitial and vascular lesions, thus providing important prognostic (and potentially therapeutic) data. In the future, the indications for renal biopsy might be extended to the definition of the histological lesions underlying the "nonalbuminuric" DKD phenotypes, as well as to the evaluation of the response to treatment with the new anti-hyperglycemic drugs that provide cardiorenal protection. CONCLUSIONS In view of the heterogeneous clinical presentation and course of DKD and of the related heterogeneous histopathological patterns, a more extensive use of renal biopsy may be crucial to provide valuable information with important pathogenic, diagnostic, prognostic, and therapeutic implications.
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Affiliation(s)
| | | | - Luca De Nicola
- Nephrology and Dialysis Unit, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Loreto Gesualdo
- Department of Emergency and Organ Transplantation, "Aldo Moro" University, Bari, Italy; Nephrology, Dialysis and Transplantation Unit, "Policlinico" University Hospital, Bari, Italy
| | - Federica Barutta
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Andrea Natali
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Unit of Internal Medicine, University Hospital, Pisa, Italy
| | - Giuseppe Penno
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Diabetes Unit, University Hospital, Pisa, Italy
| | - Paola Fioretto
- Department of Medicine, University of Padua, Padua, Italy; Unit of Medical Clinic 3, Hospital of Padua, Padua, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy; Endocrine and Metabolic Unit, Sant'Andrea University Hospital, Rome, Italy
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31
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Golea-Secara A, Munteanu C, Sarbu M, Cretu OM, Velciov S, Vlad A, Bob F, Gadalean F, Gluhovschi C, Milas O, Simulescu A, Mogos-Stefan M, Patruica M, Petrica L, Zamfir AD. Urinary proteins detected using modern proteomics intervene in early type 2 diabetic kidney disease – a pilot study. Biomark Med 2020; 14:1521-1536. [DOI: 10.2217/bmm-2020-0308] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instrument. Raw data were searched using the SEQUEST algorithm and integrated into Proteome Discoverer platform. Results & discussion: Unique peptide sequences, resulted sequence coverage, scoring of peptide spectrum matches were reported to albuminuria and databases. Five proteins that can be associated with early DKD were found: apolipoprotein AI, neutrophil gelatinase-associated lipocalin, cytidine deaminase, S100-A8 and hemoglobin subunit delta. Conclusion: Urinary proteome analysis could be used to evaluate mechanisms of pathogenesis of DKD.
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Affiliation(s)
- Alina Golea-Secara
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Cristian Munteanu
- Department of Bioinformatics & Structural Biochemistry, Institute of Biochemistry, Bucharest, Romania
| | - Mirela Sarbu
- National Institute for Research & Development in Electrochemistry & Condensed Matter, Timisoara, Romania
| | - Octavian M Cretu
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
- Department of Surgery I, Municipal Emergency Hospital Timisoara, Timisoara, Romania
| | - Silvia Velciov
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Adrian Vlad
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
- Department of Diabetes & Metabolic Diseases, County Emergency Hospital, Timisoara, Romania
| | - Flaviu Bob
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Florica Gadalean
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | | | - Oana Milas
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Anca Simulescu
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Maria Mogos-Stefan
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Mihaela Patruica
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Ligia Petrica
- Department of Nephrology, County Emergency Hospital Timisoara, Timisoara, Romania
- ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
- Centre of Translational Research & Systems Medicine, ‘Victor Babes’ University of Medicine & Pharmacy, Timisoara, Romania
| | - Alina D Zamfir
- National Institute for Research & Development in Electrochemistry & Condensed Matter, Timisoara, Romania
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Mosterd CM, Bjornstad P, van Raalte DH. Nephroprotective effects of GLP-1 receptor agonists: where do we stand? J Nephrol 2020; 33:965-975. [PMID: 32356231 PMCID: PMC7560915 DOI: 10.1007/s40620-020-00738-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 04/11/2020] [Indexed: 12/12/2022]
Abstract
Glucagon-like peptide (GLP)-1 receptor agonists are the cornerstone in the treatment of hyperglycemia in many people suffering from type 2 diabetes (T2D). These drugs have potent glucose-lowering actions and, additionally, lower body weight through satiety induction while reducing blood pressure and dyslipidemia. Partly through these actions, GLP-1 receptor agonism was shown to reduce cardiovascular disease (CVD) in people with T2D with previous CVD or at high-risk thereof. In these cardiovascular safety trials, in secondary or exploratory analyses, GLP-1 receptor agonists were also shown to reduce macro-albuminuria, an accepted surrogate marker for diabetic kidney disease (DKD), a condition that still represents a major unmet medical need. In this review we will discuss the evidence which suggests renoprotection induced by GLP-1 receptor agonists and the potential mechanisms that may be involved. These include mitigation of hyperglycemia, overweight and insulin resistance, systemic and glomerular hypertension, dyslipidemia, sodium retention, inflammation and renal hypoxia. The recently initiated large-sized FLOW trial investigating the effects of semaglutide on hard renal outcomes in patients with DKD will provide clarity whether GLP-1 receptor agonists may reduce the burden of DKD in addition to their other beneficial metabolic and cardiovascular effects.
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Affiliation(s)
- Charlotte M Mosterd
- Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Location VUMC, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Petter Bjornstad
- Section of Endocrinology, Department of Pediatrics and Division of Nephrology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Daniël H van Raalte
- Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Location VUMC, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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Xiang E, Han B, Zhang Q, Rao W, Wang Z, Chang C, Zhang Y, Tu C, Li C, Wu D. Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res Ther 2020; 11:336. [PMID: 32746936 PMCID: PMC7397631 DOI: 10.1186/s13287-020-01852-y] [Citation(s) in RCA: 183] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/01/2020] [Accepted: 07/24/2020] [Indexed: 12/11/2022] Open
Abstract
Background Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the leading cause of end-stage chronic kidney disease. Currently, there are no effective drugs for treating DN. Therefore, novel and effective strategies to ameliorate DN at the early stage should be identified. This study aimed to explore the effectiveness and underlying mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs) in DN. Methods We identified the basic biological properties and examined the multilineage differentiation potential of UC-MSCs. Streptozotocin (STZ)-induced DN rats were infused with 2 × 106 UC-MSCs via the tail vein at week 6. After 2 weeks, we measured blood glucose level, levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood, and analyzed renal pathological changes after UC-MSC treatment. We also determined the colonization of UC-MSCs in the kidney with or without STZ injection. Moreover, in vitro experiments were performed to analyze cytokine levels of renal tubular epithelial cell lines (NRK-52E, HK2) and human renal glomerular endothelial cell line (hrGECs). Results UC-MSCs significantly ameliorated functional parameters, such as 24-h urinary protein, creatinine clearance rate, serum creatinine, urea nitrogen, and renal hypertrophy index. Pathological changes in the kidney were manifested by significant reductions in renal vacuole degeneration, inflammatory cell infiltration, and renal interstitial fibrosis after UC-MSC treatment. We observed that the number of UC-MSCs recruited to the injured kidneys was increased compared with the controls. UC-MSCs apparently reduced the levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and pro-fibrotic factor (TGF-β) in the kidney and blood of DN rats. In vitro experiments showed that UC-MSC conditioned medium and UC-MSC-derived exosomes decreased the production of these cytokines in high glucose-injured renal tubular epithelial cells, and renal glomerular endothelial cells. Moreover, UC-MSCs secreted large amounts of growth factors including epidermal growth factor, fibroblast growth factor, hepatocyte growth factor, and vascular endothelial growth factor. Conclusion UC-MSCs can effectively improve the renal function, inhibit inflammation and fibrosis, and prevent its progression in a model of diabetes-induced chronic renal injury, indicating that UC-MSCs could be a promising treatment strategy for DN.
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Affiliation(s)
- E Xiang
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China.,Wuhan Hamilton Biotechnology Co., Ltd, Wuhan, China
| | - Bing Han
- Wuhan Hamilton Biotechnology Co., Ltd, Wuhan, China
| | - Quan Zhang
- Wuhan Hamilton Biotechnology Co., Ltd, Wuhan, China
| | - Wei Rao
- Wuhan Hamilton Biotechnology Co., Ltd, Wuhan, China
| | | | - Cheng Chang
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Yaqi Zhang
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Chengshu Tu
- Wuhan Hamilton Biotechnology Co., Ltd, Wuhan, China
| | - Changyong Li
- Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
| | - Dongcheng Wu
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China. .,Wuhan Hamilton Biotechnology Co., Ltd, Wuhan, China.
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Bermejo S, González E, López-Revuelta K, Ibernon M, López D, Martín-Gómez A, Garcia-Osuna R, Linares T, Díaz M, Martín N, Barros X, Marco H, Navarro MI, Esparza N, Elias S, Coloma A, Robles NR, Agraz I, Poch E, Rodas L, Lozano V, Fernández B, Hernández E, Martínez MI, Stanescu RI, Moirón JP, García N, Goicoechea M, Calero F, Bonet J, Galceran JM, Liaño F, Pascual J, Praga M, Fulladosa X, Soler MJ. Risk factors for non-diabetic renal disease in diabetic patients. Clin Kidney J 2020; 13:380-388. [PMID: 32699618 PMCID: PMC7367112 DOI: 10.1093/ckj/sfz177] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Accepted: 11/15/2019] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.
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Affiliation(s)
- Sheila Bermejo
- Nephrology Department, Hospital del Mar, Barcelona, Spain
- Nephrology Department, Fundació Althaia, Manresa, Spain
| | - Ester González
- Nephrology Department, Hospital 12 de Octubre, Madrid, Spain
| | | | - Meritxell Ibernon
- Nephrology Department, Hospital Sant Joan Despí Moisès Broggi, Barcelona, Spain
| | - Diana López
- Nephrology Department, Clínica Universitaria de Navarra, Pamplona, Spain
| | | | | | - Tania Linares
- Nephrology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | | | - Nàdia Martín
- Nephrology Department, Hospital Universitari Josep Trueta, Girona, Spain
| | - Xoana Barros
- Nephrology Department, Hospital Universitari Josep Trueta, Girona, Spain
| | - Helena Marco
- Nephrology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | | | - Noemí Esparza
- Nephrology Department, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain
| | - Sandra Elias
- Nephrology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Ana Coloma
- Nephrology Department, Hospital San Pedro, Logroño, Spain
| | | | - Irene Agraz
- Nephrology Department, Hospital Vall d’Hebron, Barcelona, Spain
| | - Esteban Poch
- Nephrology Department, Hospital Clínic, Barcelona, Spain
- IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | - Lida Rodas
- Nephrology Department, Hospital Clínic, Barcelona, Spain
- IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | - Víctor Lozano
- Nephrology Department, Hospital Clínic, Barcelona, Spain
- IDIBAPS, Universitat de Barcelona, Barcelona, Spain
| | | | | | | | | | - José Pelayo Moirón
- Nephrology Department, Clínica Universitaria de Navarra, Pamplona, Spain
| | - Núria García
- Nephrology Department, Clínica Universitaria de Navarra, Pamplona, Spain
| | - Marian Goicoechea
- Nephrology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | | | - Josep Bonet
- Nephrology Department, Hospital Germans Trias i Pujol, Badalona, Spain
| | | | - Fernando Liaño
- Nephrology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | - Manuel Praga
- Nephrology Department, Hospital 12 de Octubre, Madrid, Spain
| | - Xavier Fulladosa
- Nephrology Department, Hospital de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain; Spanish Group for the Study of Glomerular Diseases (GLOSEN), Grup de Treball de Malalties Glomerulars de la Societat Catalana de. Nefrologia (GlomCAT), and Grupo Español de Estudio de Nefropatía Diabética (GEENDIAB)
| | - María José Soler
- Nephrology Department, Hospital del Mar, Barcelona, Spain
- Nephrology Department, Hospital Vall d’Hebron, Barcelona, Spain
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Souza DA, Silva GEB, Fernandes IL, de Brito DJA, Muniz MPR, Neto OMV, Costa RS, Dantas M, Neto MM. The Prevalence of Nondiabetic Renal Diseases in Patients with Diabetes Mellitus in the University Hospital of Ribeirão Preto, São Paulo. J Diabetes Res 2020; 2020:2129459. [PMID: 32626777 PMCID: PMC7312549 DOI: 10.1155/2020/2129459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/25/2020] [Accepted: 05/18/2020] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To evaluate the prevalence of nondiabetic renal diseases (NDRDs) in renal biopsies of patients with diabetes mellitus (DM) in the University Hospital of Ribeirão Preto, São Paulo. Research Design and Methods. We conducted a retrospective study including kidney biopsies performed in diabetic patients between 1987 and 2013. We evaluated 79 biopsies during this period. The primary variable was the prevalence of NDRD in patients with DM. The secondary variables were the presence of systemic arterial hypertension (SAH), hematuria, time since diagnosis of DM, serum creatinine, and proteinuria levels. The cases were divided into the following groups: isolated diabetic nephropathy (DN-group I), isolated nondiabetic renal diseases (NDRD-group II), associated NDRD/DN (group III), and associated NDRD+NDRD/DN (group IV). RESULTS Most of the patients (58.22%) presented only alterations arising from DN. NDRDs were present in 41.77% of the patients. Membranous glomerulonephritis (30.3%) and IgA nephropathy (24.24%) were the most prevalent NDRDs. We found no differences between female and male patients with NDRD when assessing the secondary variables. A time since diagnosis of five years or less revealed a statistical difference (p = 0.0005) in the comparison between the isolated DN (group I) and the NDRD+NDRD/DN (group IV). The other secondary variables were not significant in the comparison of the groups. CONCLUSIONS We concluded that the prevalence of NDRD is 41.77%. Membranous glomerulonephritis was the most prevalent NDRD in our study. We also conclude that the probability of the presence of NDRD with or without concomitant DN is greater for patients who had biopsies with a time since diagnosis of five years or less. A time since diagnosis of ten years or more does not allow the exclusion of the presence of NDRD.
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Affiliation(s)
- Diego Agra Souza
- Pathology Service of the Ribeirão Preto Medical School Hospital, University of São Paulo, São Paulo, Brazil
| | - Gyl Eanes Barros Silva
- Pathology Service of the Ribeirão Preto Medical School Hospital, University of São Paulo, São Paulo, Brazil
| | - Igor Lima Fernandes
- Pathology Service of the Ribeirão Preto Medical School Hospital, University of São Paulo, São Paulo, Brazil
| | | | | | | | - Roberto Silva Costa
- Laboratory of Renal Pathology, Nephrology Division, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Márcio Dantas
- Nephrology Division, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Miguel Moyses Neto
- Nephrology Division, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
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García-Martín F, González Monte E, Hernández Martínez E, Bada Boch T, Bustamante Jiménez NE, Praga Terente M. When to perform renal biopsy in patients with type2 diabetes mellitus? Predictive model of non-diabetic renal disease. Nefrologia 2019; 40:180-189. [PMID: 31761446 DOI: 10.1016/j.nefro.2019.07.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 06/20/2019] [Accepted: 07/16/2019] [Indexed: 01/31/2023] Open
Abstract
INTRODUCTION Diabetic nephropathy (DN) is one of the most frequent complications in patients with diabetes mellitus (DM) and its diagnosis is usually established on clinical grounds. However, kidney involvement in some diabetic patients can be due to other causes, and renal biopsy might be needed to exclude them. The aim of our study was to establish the clinical and analytical data that predict DN and no-diabetic renal disease (NDRD), and to develop a predictive model (score) to confirm or dismiss DN. MATERIAL AND METHODS We conducted a transversal, observational and retrospective study, including renal biopsies performed in type2 DM patients, between 2000 and 2018. RESULTS Two hundred seven DM patients were included in our study. The mean age was 64.5±10.6 years and 74% were male. DN was found in 126 (61%) of the biopsies and NDRD in 81 (39%). Diabetic retinopathy was presented in 58% of DN patients, but only in 6% of NDRD patients (P<.001). Patients with NDRD were diagnosed of primary glomerulopathies (52%), nephroangiosclerosis (16%), inmunoallergic interstitial nephritis (15%) and vasculitis (8.5%). In the multivariate analysis, retinopathy (OR26.7; 95%CI: 6.8-104.5), chronic ischaemia of lower limbs (OR4,37; 95%CI: 1.33-14.3), insulin therapy (OR3.05; 95%CI: 1.13-8.25), time course of DM ≥10years (OR2.71; 95%CI: 1.1-6.62) and nephrotic range proteinuria (OR2.91; 95%CI: 1.2-7.1) were independent predictors for DN. Microhaematuria defined as ≥10 red blood cells per high-power field (OR0.032; 95%CI: 0.01-0.11) and overweight (OR0.21; 95%CI: 0.08-0.5) were independent predictors of NDRD. According to the predictive model based on the multivariate analysis, all patients with a score >3 had DN and 94% of cases with a score ≤1 had NDRD (score ranked from -6 to 8points). CONCLUSIONS NDRD is common in DM patients (39%), being primary glomerulonephritis the most frequent ethology. The absence of retinopathy and the presence of microhematuria are highly suggestive of NDRD. The use of our predictive model could facilitate the indication of performing a renal biopsy in DM patients.
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Affiliation(s)
- Florencio García-Martín
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España; Departamento de Medicina, Universidad Complutense, Madrid, España.
| | | | | | - Teresa Bada Boch
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España
| | | | - Manuel Praga Terente
- Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España; Departamento de Medicina, Universidad Complutense, Madrid, España
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Palygin O, Spires D, Levchenko V, Bohovyk R, Fedoriuk M, Klemens CA, Sykes O, Bukowy JD, Cowley AW, Lazar J, Ilatovskaya DV, Staruschenko A. Progression of diabetic kidney disease in T2DN rats. Am J Physiol Renal Physiol 2019; 317:F1450-F1461. [PMID: 31566426 DOI: 10.1152/ajprenal.00246.2019] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Diabetic kidney disease (DKD) is one of the leading pathological causes of decreased renal function and progression to end-stage kidney failure. To explore and characterize age-related changes in DKD and associated glomerular damage, we used a rat model of type 2 diabetic nephropathy (T2DN) at 12 wk and older than 48 wk. We compared their disease progression with control nondiabetic Wistar and diabetic Goto-Kakizaki (GK) rats. During the early stages of DKD, T2DN and GK animals revealed significant increases in blood glucose and kidney-to-body weight ratio. Both diabetic groups had significantly altered renin-angiotensin-aldosterone system function. Thereafter, during the later stages of disease progression, T2DN rats demonstrated a remarkable increase in renal damage compared with GK and Wistar rats, as indicated by renal hypertrophy, polyuria accompanied by a decrease in urine osmolarity, high cholesterol, a significant prevalence of medullary protein casts, and severe forms of glomerular injury. Urinary nephrin shedding indicated loss of the glomerular slit diaphragm, which also correlates with the dramatic elevation in albuminuria and loss of podocin staining in aged T2DN rats. Furthermore, we used scanning ion microscopy topographical analyses to detect and quantify the pathological remodeling in podocyte foot projections of isolated glomeruli from T2DN animals. In summary, T2DN rats developed renal and physiological abnormalities similar to clinical observations in human patients with DKD, including progressive glomerular damage and a significant decrease in renin-angiotensin-aldosterone system plasma levels, indicating these rats are an excellent model for studying the progression of renal damage in type 2 DKD.
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Affiliation(s)
- Oleg Palygin
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Denisha Spires
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Vladislav Levchenko
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Ruslan Bohovyk
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Mykhailo Fedoriuk
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Christine A Klemens
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Olga Sykes
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - John D Bukowy
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Allen W Cowley
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Jozef Lazar
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Daria V Ilatovskaya
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Alexander Staruschenko
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin.,Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin
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38
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Anguiano Gómez L, Lei Y, Kumar Devarapu S, Anders HJ. The diabetes pandemic suggests unmet needs for 'CKD with diabetes' in addition to 'diabetic nephropathy'-implications for pre-clinical research and drug testing. Nephrol Dial Transplant 2019; 33:1292-1304. [PMID: 28992221 DOI: 10.1093/ndt/gfx219] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 05/21/2017] [Indexed: 12/12/2022] Open
Abstract
Curing 'diabetic nephropathy' is considered an unmet medical need of high priority. We propose to question the concept of 'diabetic nephropathy' that implies diabetes as the predominant cause of kidney disease, which may not apply to the majority of type 2 diabetics approaching end-stage kidney disease. With the onset of diabetes, hyperglycaemia/sodium-glucose co-transporter-2-driven glomerular hyperfiltration promotes nephron hypertrophy, which, however, on its own, causes proteinuria not before a decade later, probably because podocyte hypertrophy can usually accommodate an increase in the filtration surface. In contrast, precedent chronic kidney disease (CKD), that is, few nephrons per body mass, e.g. due to poor nephron endowment from birth, obesity, pregnancy, or renal ageing or injury-related nephron loss, usually precedes the onset of type 2 diabetes. This applies in particular in older adults, and each on its own, but especially in combination, further aggravates single nephron hyperfiltration and glomerular hypertrophy. Whenever this additional hyperglycaemia-driven enlargement of the glomerular filtration surface exceeds the capacity of podocytes for hypertrophy, podocytes detachment leads to glomerulosclerosis and nephron loss, i.e. CKD progression. Animal models of 'diabetic nephropathy' based only on hyperglycaemia do not mimic this aspect and therefore poorly predict outcomes of clinical trials usually performed on elderly CKD patients with type 2 diabetes. Thus, we advocate the use of renal mass (nephron) ablation in type 2 diabetic animals to better mimic the pathophysiology of 'CKD with diabetes' in the target patient population and the use of the glomerular filtration rate as a primary endpoint to more reliably predict trial outcomes.
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Affiliation(s)
- Lidia Anguiano Gómez
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.,Department of Nephrology, Hospital del Mar-IMIM, Barcelona, Spain
| | - Yutian Lei
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
| | - Satish Kumar Devarapu
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
| | - Hans-Joachim Anders
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
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Kopel J, Pena-Hernandez C, Nugent K. Evolving spectrum of diabetic nephropathy. World J Diabetes 2019; 10:269-279. [PMID: 31139314 PMCID: PMC6522757 DOI: 10.4239/wjd.v10.i5.269] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 05/13/2019] [Accepted: 05/13/2019] [Indexed: 02/05/2023] Open
Abstract
Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy (DN), which classically presents with proteinuria followed by a progressive decrease in renal function. However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as non-proteinuric DN (NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.
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Affiliation(s)
- Jonathan Kopel
- Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79416, United States
| | - Camilo Pena-Hernandez
- Department of Internal Medicine, Division of Nephrology, Lubbock, TX 79430, United States
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
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40
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Singh N, Pattanashetti N, Joshi K, Kohli HS, Gupta KL, Ramachandran R. Missed Monoclonal Disease Manifesting in Early Post-renal Transplant Period. Indian J Nephrol 2019; 29:65-69. [PMID: 30814798 PMCID: PMC6375021 DOI: 10.4103/ijn.ijn_384_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
A 63-year-old diabetic gentleman with microvascular complications presented with advanced azotemia and anemia. He was stabilized with blood transfusion and hemodialysis. With the probable diagnosis of diabetic nephropathy-related end-stage renal disease, he underwent kidney transplantation. He had delayed graft function. Graft biopsy done on the 2nd postoperative day showed acute tubular necrosis. Graft biopsy repeated after 2 weeks for persistent graft dysfunction showed myeloma cast nephropathy (MCN) and light chain proximal tubulopathy. Work-up for multiple myeloma was positive. He was started on plasmapheresis and chemotherapy. However, he suffered sudden cardiac death during dialysis after 1 week. The presence of MCN in the early graft biopsy implies that it must have been the cause for his native kidney failure. Thus, renal failure in a diabetic should not always be presumed to be due to diabetic nephropathy, and kidney biopsy should be done in diabetics with atypical features.
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Affiliation(s)
- N Singh
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - N Pattanashetti
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - K Joshi
- Department of Pathology, Medicos Centre, Chandigarh, India
| | - H S Kohli
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - K L Gupta
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - R Ramachandran
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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41
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Arora MK, Sarup Y, Tomar R, Singh M, Kumar P. Amelioration of Diabetes-Induced Diabetic Nephropathy by Aloe vera: Implication of Oxidative Stress and Hyperlipidemia. J Diet Suppl 2018; 16:227-244. [PMID: 29621403 DOI: 10.1080/19390211.2018.1449159] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This study investigated the effect of Aloe vera in diabetes-induced nephropathy in rats. As diabetes-associated hyperlipidemia and oxidative stress have been implicated in the pathogenesis of diabetic nephropathy, we evaluated the protective effect of whole leaf extract of Aloe vera on the basis of its hypolipidemic and antioxidative property. Aloe vera (300 mg/kg orally) has been noted to possess renoprotective effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. Rats were administered streptozotocin (STZ) (55 mg/kg intraperitoneally once) to induce experimental diabetes mellitus. The development of diabetic nephropathy was assessed biochemically and histologically. In addition, the diabetes-induced lipid profile and renal oxidative stress were assessed. The single administration of STZ produced diabetes, which induced renal oxidative stress, altered the lipid profile, and subsequently produced nephropathy in eight weeks by increasing serum creatinine, blood urea nitrogen, proteinuria, and glomerular damage. Treatment with Aloe vera (300 mg/kg/day orally) was noted to be more effective against the diabetes-induced nephropathy and renal oxidative stress as compared to lisinopril (1 mg/kg/day orally), a reference agent. It may be concluded that diabetes-induced oxidative stress and lipid alterations may be accountable for the induction of nephropathy in diabetic rats. The treatment with Aloe vera (300 mg/kg/day orally) may have prevented the development of diabetes-induced nephropathy by reducing lipid alteration, decreasing renal oxidative stress, and providing direct renoprotective action.
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Affiliation(s)
| | - Yogesh Sarup
- a Department of Pharmacognosy , KIET School of Pharmacy , Ghaziabad , India
| | - Ritu Tomar
- b Department of Pharmacognosy , Swami Vivekanand Subharti University , Meerut , India
| | - Mary Singh
- a Department of Pharmacognosy , KIET School of Pharmacy , Ghaziabad , India
| | - Puspendra Kumar
- c Department of Pharamocognosy , KIET School of Pharmacy , Ghaziabad , India
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Malerbi FK, Regatieri CV, de Sa JR, Morales PH, Farah ME, Dib SA. Retinal malperfusion in albuminuric Type 1 diabetes mellitus patients without clinical signs of diabetic retinopathy: a prospective pilot study. Int J Retina Vitreous 2017; 3:49. [PMID: 29270314 PMCID: PMC5733928 DOI: 10.1186/s40942-017-0102-y] [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: 09/20/2017] [Accepted: 11/06/2017] [Indexed: 11/13/2022] Open
Abstract
Background To report fluorescein angiography findings in a group of albuminuric Type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy. Methods Fifteen albuminuric T1DM patients with normal/near normal estimated glomerular filtration rate without diabetic retinopathy underwent fluorescein angiography; presence of microaneurysms, vascular permeability changes and retinal malperfusion were evaluated. Results Fluorescein angiography revealed microaneurysms, blood-retinal barrier breakdown and retinal ischemia in 10 (67%) and 11 (73%); 8 (53%) and 9 (60%); 2 (13%) and 5 (33%) of patients at baseline and follow up, respectively. Follow up time averaged 24.6 months, minimum follow up time was 20 months. Patients who presented retinal malperfusion had higher HbA1C and lower estimated glomerular filtration rate. Conclusions Most albuminuric T1DM patients with a normal fundus exam had angiographic signs of diabetic retinopathy, some presenting retinal malperfusion. Retinal changes may be found with more sensitive testing in these patients, especially with impaired estimated glomerular filtration rate, even if the fundus exam is normal, and fluorescein angiography should be considered. These findings point to a homogenous presentation of the diabetic microangiopathies. Electronic supplementary material The online version of this article (10.1186/s40942-017-0102-y) contains supplementary material, which is available to authorized users.
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43
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Gala-Błądzińska A, Dumnicka P, Kuśnierz-Cabala B, Rybak K, Drożdż R, Żyłka A, Kuźniewski M. Urinary Neutrophil Gelatinase-Associated Lipocalin Is Complementary to Albuminuria in Diagnosis of Early-Stage Diabetic Kidney Disease in Type 2 Diabetes. BIOMED RESEARCH INTERNATIONAL 2017; 2017:4691389. [PMID: 28845433 PMCID: PMC5563398 DOI: 10.1155/2017/4691389] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 03/19/2017] [Accepted: 07/06/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND Two clinical phenotypes of diabetic kidney disease (DKD) have been reported, that is, with or without increased albuminuria. The aim of study was to assess the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for the early diagnosis of DKD in the type 2 diabetes mellitus (T2DM). METHODS The study group consisted of 123 patients with T2DM (mean age 62 ± 14 years), with urine albumin/creatinine ratio (uACR) < 300 mg/g and eGFR ≥ 60 ml/min/1.73 m2. The control group included 22 nondiabetic patients with comparable age, sex, and comorbidities. uNGAL, albumin, and creatinine were measured in the first morning urine samples. uACR and uNGAL/creatinine ratios (uNCR) were calculated. RESULTS In the control group, maximum uNCR was 39.64 µg/g. In T2DM group, 24 patients (20%) had higher results, with the maximum value of 378.6 µg/g. Among patients with uNCR > 39.64 µg/g, 13 (54%) did not have markedly increased albuminuria. Women with T2DM had higher uNCR than men (p < 0.001), without difference in uACR (p = 0.09). uNCR in T2DM patients correlated significantly with HbA1c. Sex, total cholesterol, and uACR were independent predictors of uNCR above 39.64 µg/g. CONCLUSIONS Increased uNGAL and uNCR may indicate early tubular damage, associated with dyslipidemia and worse diabetes control, especially in females with T2DM.
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Affiliation(s)
- Agnieszka Gala-Błądzińska
- Department of Dialysis and Nephrology, St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszów, Lwowska 60 Street, 35-301 Rzeszów, Poland
| | - Paulina Dumnicka
- Department of Medical Diagnostics, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Beata Kuśnierz-Cabala
- Department of Diagnostics, Chair of Clinical Biochemistry, Jagiellonian University Medical College, 15A Kopernika Street, 31-501 Krakow, Poland
| | - Katarzyna Rybak
- Department of Internal Medicine, Nephrology & Endocrinology, St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszów, Lwowska 60 Street, 35-301 Rzeszów, Poland
| | - Ryszard Drożdż
- Department of Medical Diagnostics, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
| | - Agnieszka Żyłka
- St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszów, Lwowska 60 Street, 35-301 Rzeszów, Poland
| | - Marek Kuźniewski
- Department of Nephrology, Jagiellonian University Medical College, 15 Kopernika Street, 31-501 Krakow, Poland
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Yang JK, Wang YY, Liu C, Shi TT, Lu J, Cao X, Yang FY, Feng JP, Chen C, Ji LN, Xu A. Urine Proteome Specific for Eye Damage Can Predict Kidney Damage in Patients With Type 2 Diabetes: A Case-Control and a 5.3-Year Prospective Cohort Study. Diabetes Care 2017; 40:253-260. [PMID: 27903615 DOI: 10.2337/dc16-1529] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 11/16/2016] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The predictive value of microalbuminuria (MAU) for kidney damage is limited in type 2 diabetes (T2D). We studied whether a urine proteome specific for sight-threatening proliferative diabetic retinopathy (PDR) is an indicator to predict chronic renal insufficiency (CRI) in patients with T2D. RESEARCH DESIGN AND METHODS A shotgun urine proteomic analysis was performed in patients with MAU and PDR (case subjects) and in patients with MAU and a duration of T2D for >10 years but without any degree of retinopathy (control subjects). In the cohort study, 210 patients with T2D with an estimated glomerular filtration rate (eGFR) ≥80 mL/min/1.73 m2 were followed for a median of 5.3 years. Urine proteins specific for PDR were used for predicting CRI (eGFR <60 mL/min/1.73 m2). RESULTS The top two urine proteins with the highest difference in ratio of case subjects to control subjects were haptoglobin (8.7 times; P < 0.0001) and α-2-macroglobulin (5.7 times; P < 0.0001). In the cohort study, patients with baseline urinary haptoglobin ≥20 ng/min (haptoglobinuria) had a higher incidence of CRI than those without (hazard ratio [95% CI] 3.27 [1.41-7.58]; P = 0.006). The overall CRI rate was 3.2% for patients without haptoglobinuria or MAU, 9.5% for those with MAU, and 13.3% for those with haptoglobinuria. The highest rate for CRI (22.4%) was in patients with both MAU and haptoglobinuria (P < 0.001). CONCLUSIONS Urine haptoglobin, which is specific for PDR, is a novel biomarker and complement to urine albumin for predicting kidney damage in patients with T2D.
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Affiliation(s)
- Jin-Kui Yang
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ying-Ying Wang
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chang Liu
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ting-Ting Shi
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jing Lu
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xi Cao
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Fang-Yuan Yang
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jian-Ping Feng
- Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Chen Chen
- School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
| | - Li-Nong Ji
- Endocrinology and Metabolism Department, Peking University People's Hospital, Beijing, China
| | - Aimin Xu
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, University of Hong Kong, Hong Kong
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Bermejo S, Pascual J, Soler MJ. The large spectrum of renal disease in diabetic patients. Clin Kidney J 2017; 10:255-256. [PMID: 28396743 PMCID: PMC5381242 DOI: 10.1093/ckj/sfw137] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 11/14/2016] [Indexed: 12/13/2022] Open
Abstract
The prevalence of diabetic nephropathy (DN) among diabetic patients seems to be overestimated. Recent studies with renal biopsies show that the incidence of non-diabetic nephropathy (NDN) among diabetic patients is higher than expected. Renal impairment of diabetic patients is frequently attributed to DN without meeting the KDOQI criteria or performing renal biopsy to exclude NDN. In this editorial, we update the spectrum of renal disease in diabetic patients and the impact on diagnosis, prognosis and therapy.
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Affiliation(s)
- Sheila Bermejo
- Department of Nephrology, Hospital del Mar, Barcelona, Spain; Department of Nephrology, Consorci Sanitari del Garraf, Vilanova I la Geltrú, Spain; Department of Nephrology, Fundació Althaia, Manresa, Spain
| | - Julio Pascual
- Department of Nephrology, Hospital del Mar, Barcelona, Spain; Institut Mar for Medical Research (IMIM), Barcelona, Spain
| | - Maria José Soler
- Department of Nephrology, Hospital del Mar, Barcelona, Spain; Institut Mar for Medical Research (IMIM), Barcelona, Spain
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Qi C, Mao X, Zhang Z, Wu H. Classification and Differential Diagnosis of Diabetic Nephropathy. J Diabetes Res 2017; 2017:8637138. [PMID: 28316995 PMCID: PMC5337846 DOI: 10.1155/2017/8637138] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 01/26/2017] [Indexed: 11/18/2022] Open
Abstract
Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review.
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Affiliation(s)
- Chenyang Qi
- Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xing Mao
- Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhigang Zhang
- Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Institute for Kidneys and Dialysis, Shanghai, China
| | - Huijuan Wu
- Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Institute for Kidneys and Dialysis, Shanghai, China
- *Huijuan Wu:
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Nath S, Ghosh SK, Choudhury Y. A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans. J Pharmacol Toxicol Methods 2016; 84:20-30. [PMID: 27773844 DOI: 10.1016/j.vascn.2016.10.007] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 10/04/2016] [Accepted: 10/19/2016] [Indexed: 01/07/2023]
Abstract
INTRODUCTION A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg-1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg-1 bw daily) and metformin (50mgkg-1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. RESULTS Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. DISCUSSION A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening.
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Affiliation(s)
- Sayantan Nath
- Department of Biotechnology, Assam University, Silchar, 788011, India
| | | | - Yashmin Choudhury
- Department of Biotechnology, Assam University, Silchar, 788011, India.
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Bermejo S, Soler MJ, Gimeno J, Barrios C, Rodríguez E, Mojal S, Pascual J. Predictive factors for non-diabetic nephropathy in diabetic patients. The utility of renal biopsy. Nefrologia 2016; 36:535-544. [PMID: 27523263 DOI: 10.1016/j.nefro.2016.06.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 05/22/2016] [Accepted: 06/25/2016] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Diabetic renal lesions can only be diagnosed by kidney biopsy. These biopsies have a high prevalence of non-diabetic lesions. The aims of the study were to determine the predictability of non-diabetic nephropathy (NDN) in diabetics and study differences in survival and renal prognosis. In addition, we evaluated histological lesions and the effect of proteinuria on survival and renal prognosis in patients with diabetic nephropathy (DN). MATERIAL AND METHODS A descriptive, retrospective study of kidney biopsies of diabetics between 1990 and 2013 in our centre. RESULTS 110 patients were included in the study: 87 men (79%), mean age 62 years (50-74), mean serum creatinine 2.6mg/dl (0.9-4.3) and proteinuria 3.5g/24hours (0.5-6.5). 61.8% showed NDN, 34.5% showed DN and 3,6% showed DN+NDN. The most common NDN was IgA nephropathy (13,2%). In the multivariate analysis, creatinine (OR: 1.48, 1.011-2.172, p=0.044), proteinuria/24hours (OR: 0.813, 0.679-0.974, p=0.025), duration of diabetes (OR: 0.992, 0.987-0.998, p=0.004), age (OR: 1.068, 95% CI: 1.010-1.129, p=0.022), and diabetic retinopathy (OR: 0.23, 0.066-0.808, p=0.022) were independently associated with NDN. We did not find any differences in survival or renal prognosis. Concerning patients with DN, increased nodular mesangial expansion (p=0.02) and worse renal prognosis (p=0.004) were observed in nephrotic proteinuria as compared to non-nephrotic proteinuria. We did not find differences in patient survival. CONCLUSIONS The most common cause of NDN was IgA nephropathy. Higher creatinine levels, shorter duration of diabetes, absence of diabetic retinopathy, lower proteinuria, and older age were risk factors for NDN. Patients with DN and nephrotic-range proteinuria had worse renal prognosis.
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Affiliation(s)
- Sheila Bermejo
- Servicio de Nefrología, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España
| | - María José Soler
- Servicio de Nefrología, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España.
| | - Javier Gimeno
- Servicio de Anatomía Patológica, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España
| | - Clara Barrios
- Servicio de Nefrología, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España
| | - Eva Rodríguez
- Servicio de Nefrología, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España
| | - Sergi Mojal
- Fundación IMIM, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España
| | - Julio Pascual
- Servicio de Nefrología, Hospital del Mar, REDINREN RD12/0021/0024, Barcelona, España
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Lin CH, Chang YC, Chuang LM. Early detection of diabetic kidney disease: Present limitations and future perspectives. World J Diabetes 2016; 7:290-301. [PMID: 27525056 PMCID: PMC4958689 DOI: 10.4239/wjd.v7.i14.290] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 05/29/2016] [Accepted: 06/29/2016] [Indexed: 02/05/2023] Open
Abstract
Diabetic kidney disease (DKD) is one of the most common diabetic complications, as well as the leading cause of chronic kidney disease and end-stage renal disease around the world. To prevent the dreadful consequence, development of new assays for diagnostic of DKD has always been the priority in the research field of diabetic complications. At present, urinary albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) are the standard methods for assessing glomerular damage and renal function changes in clinical practice. However, due to diverse tissue involvement in different individuals, the so-called “non-albuminuric renal impairment” is not uncommon, especially in patients with type 2 diabetes. On the other hand, the precision of creatinine-based GFR estimates is limited in hyperfiltration status. These facts make albuminuria and eGFR less reliable indicators for early-stage DKD. In recent years, considerable progress has been made in the understanding of the pathogenesis of DKD, along with the elucidation of its genetic profiles and phenotypic expression of different molecules. With the help of ever-evolving technologies, it has gradually become plausible to apply the thriving information in clinical practice. The strength and weakness of several novel biomarkers, genomic, proteomic and metabolomic signatures in assisting the early diagnosis of DKD will be discussed in this article.
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50
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Zhu X, Xiong X, Yuan S, Xiao L, Fu X, Yang Y, Tang C, He L, Liu F, Sun L. Validation of the interstitial fibrosis and tubular atrophy on the new pathological classification in patients with diabetic nephropathy: A single-center study in China. J Diabetes Complications 2016; 30:537-41. [PMID: 26796433 DOI: 10.1016/j.jdiacomp.2015.12.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 12/01/2015] [Accepted: 12/01/2015] [Indexed: 10/22/2022]
Abstract
OBJECTIVES The association between interstitial fibrosis and tubular atrophy (IFTA) and the clinical outcomes in diabetic nephropathy (DN) remains unclear. This study is to evaluate the clinical predictors and renal prognosis of IFTA score in patients with DN. METHODS 52 cases with DN with renal biopsy were divided into three groups according to IFTA score. The χ2 test or Fisher's exact test, Mann-Whitney U-test, Kruskal-Wallis H-test and Spearman's correlation analysis were used in this subject. Ordinal regression mode was utilized to evaluate which clinical factors might be the predictors of IFTA score. RESULTS Compared to IFTA score 1 group, the patients in score 3 were younger and have greatly lower level of eGFR and hemoglobin and higher serum creatinine (p<0.01). A close relationship between the clinical findings and IFTA was observed, such as IFTA with eGFR(r=-0.58, P<0.01), triglyceride(r=-0.29, P=0.04), Hb (r=-0.38, P<0.01), systolic blood pressure (r=0.29, P=0.04) and urinary protein level (r=0.46, P<0.01); in addition, eGFR (OR 0.31 (95%Cl -1.883 to -0.485) p=0.001) showed statistical significance with IFTA. The 5-year renal survival rate was estimated as 100% in IFTA score 0, 88.9% in score 1, 76.9% in score 2, and 20.0% in score 3. Furthermore, greatly lower level of eGFR, and higher serum creatinine and BUN in the glomerular class IV were seen (p<0.01 vs class II), with positive correlation with IFTA (r=0.51, P<0.01). CONCLUSION The renal pathologic diagnosis in IFTA score was a good predictor for renal prognosis in type II DM. eGFR might be a predictor of IFTA in patients with DN.
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Affiliation(s)
- Xuejing Zhu
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiaofen Xiong
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Shuguang Yuan
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Xiao
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiao Fu
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yuan Yang
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chengyuan Tang
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Liyu He
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fuyou Liu
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lin Sun
- Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
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