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Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy

OBJECTIVES: Converging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investig...

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Autores principales: Jiang, Shimin, Di, Dingxin, Jiao, Yuanyuan, Zou, Guming, Gao, Hongmei, Li, Wenge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196586/
https://www.ncbi.nlm.nih.gov/pubmed/35711407
http://dx.doi.org/10.3389/fimmu.2022.868127
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author Jiang, Shimin
Di, Dingxin
Jiao, Yuanyuan
Zou, Guming
Gao, Hongmei
Li, Wenge
author_facet Jiang, Shimin
Di, Dingxin
Jiao, Yuanyuan
Zou, Guming
Gao, Hongmei
Li, Wenge
author_sort Jiang, Shimin
collection PubMed
description OBJECTIVES: Converging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function. METHODS: The study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death. RESULTS: None of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08–2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14–13.17) vs. 2.46 (95% CI, 0.68–8.89)] or III [HR, 4.98 (95% CI, 1.53–16.23) vs. 2.63 (95% CI, 0.77–9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only. CONCLUSIONS: Complement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification.
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spelling pubmed-91965862022-06-15 Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy Jiang, Shimin Di, Dingxin Jiao, Yuanyuan Zou, Guming Gao, Hongmei Li, Wenge Front Immunol Immunology OBJECTIVES: Converging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function. METHODS: The study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death. RESULTS: None of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08–2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14–13.17) vs. 2.46 (95% CI, 0.68–8.89)] or III [HR, 4.98 (95% CI, 1.53–16.23) vs. 2.63 (95% CI, 0.77–9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only. CONCLUSIONS: Complement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9196586/ /pubmed/35711407 http://dx.doi.org/10.3389/fimmu.2022.868127 Text en Copyright © 2022 Jiang, Di, Jiao, Zou, Gao and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Jiang, Shimin
Di, Dingxin
Jiao, Yuanyuan
Zou, Guming
Gao, Hongmei
Li, Wenge
Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
title Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
title_full Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
title_fullStr Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
title_full_unstemmed Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
title_short Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy
title_sort complement deposition predicts worsening kidney function and underlines the clinical significance of the 2010 renal pathology society classification of diabetic nephropathy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196586/
https://www.ncbi.nlm.nih.gov/pubmed/35711407
http://dx.doi.org/10.3389/fimmu.2022.868127
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