Complement Activation in Patients With Diabetic Nephropathy

Complement activation plays a role in various organs in patients with diabetes. However, in diabetic nephropathy (DN), the role of complement activation is poorly understood. We examined the prevalence and clinical significance of complement deposits in the renal tissue of cases with type 1 and type...

Full description

Bibliographic Details
Main Authors: Pascal Bus, Jamie S. Chua, Céline Q.F. Klessens, Malu Zandbergen, Ron Wolterbeek, Cees van Kooten, Leendert A. Trouw, Jan A. Bruijn, Hans J. Baelde
Format: Article
Language:English
Published: Elsevier 2018-03-01
Series:Kidney International Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468024917304230
_version_ 1819161173850849280
author Pascal Bus
Jamie S. Chua
Céline Q.F. Klessens
Malu Zandbergen
Ron Wolterbeek
Cees van Kooten
Leendert A. Trouw
Jan A. Bruijn
Hans J. Baelde
author_facet Pascal Bus
Jamie S. Chua
Céline Q.F. Klessens
Malu Zandbergen
Ron Wolterbeek
Cees van Kooten
Leendert A. Trouw
Jan A. Bruijn
Hans J. Baelde
author_sort Pascal Bus
collection DOAJ
description Complement activation plays a role in various organs in patients with diabetes. However, in diabetic nephropathy (DN), the role of complement activation is poorly understood. We examined the prevalence and clinical significance of complement deposits in the renal tissue of cases with type 1 and type 2 diabetes with and without DN. Methods: We measured the prevalence of glomerular C4d, C1q, mannose-binding lectin (MBL), and C5b-9 deposits in 101 autopsied diabetic cases with DN, 59 autopsied diabetic cases without DN, and 41 autopsied cases without diabetes or kidney disease. The presence of complement deposits was scored by researchers who were blinded with respect to the clinical and histological data. Results: C4d deposits were more prevalent in cases with DN than in cases without DN in both the glomeruli (46% vs. 26%) and the arterioles (28% vs. 12%). C1q deposits were also increased in the glomerular hili (77% vs. 55%) and arterioles (33% vs.14%), and were correlated with DN (P < 0.01). MBL deposits were only rarely observed. C5b-9 deposits were more prevalent in the cases with diabetes mellitus (DM) than in the cases without DM (69% vs. 32%; P < 0.001). Finally, glomerular C4d and C5b-9 deposits were correlated with the severity of DN (ρ = 0.341 and 0.259, respectively; P < 0.001). Conclusion: Complement activation is correlated with both the presence and severity of DN, suggesting that the complement system is involved in the development of renal pathology in patients with diabetes and is a promising target for inhibiting and/or preventing DN in these patients.
first_indexed 2024-12-22T17:08:08Z
format Article
id doaj.art-731a58d0746246f8bf1f96f346fdf8bd
institution Directory Open Access Journal
issn 2468-0249
language English
last_indexed 2024-12-22T17:08:08Z
publishDate 2018-03-01
publisher Elsevier
record_format Article
series Kidney International Reports
spelling doaj.art-731a58d0746246f8bf1f96f346fdf8bd2022-12-21T18:19:08ZengElsevierKidney International Reports2468-02492018-03-013230231310.1016/j.ekir.2017.10.005Complement Activation in Patients With Diabetic NephropathyPascal Bus0Jamie S. Chua1Céline Q.F. Klessens2Malu Zandbergen3Ron Wolterbeek4Cees van Kooten5Leendert A. Trouw6Jan A. Bruijn7Hans J. Baelde8Department of Pathology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Nephrology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, The NetherlandsComplement activation plays a role in various organs in patients with diabetes. However, in diabetic nephropathy (DN), the role of complement activation is poorly understood. We examined the prevalence and clinical significance of complement deposits in the renal tissue of cases with type 1 and type 2 diabetes with and without DN. Methods: We measured the prevalence of glomerular C4d, C1q, mannose-binding lectin (MBL), and C5b-9 deposits in 101 autopsied diabetic cases with DN, 59 autopsied diabetic cases without DN, and 41 autopsied cases without diabetes or kidney disease. The presence of complement deposits was scored by researchers who were blinded with respect to the clinical and histological data. Results: C4d deposits were more prevalent in cases with DN than in cases without DN in both the glomeruli (46% vs. 26%) and the arterioles (28% vs. 12%). C1q deposits were also increased in the glomerular hili (77% vs. 55%) and arterioles (33% vs.14%), and were correlated with DN (P < 0.01). MBL deposits were only rarely observed. C5b-9 deposits were more prevalent in the cases with diabetes mellitus (DM) than in the cases without DM (69% vs. 32%; P < 0.001). Finally, glomerular C4d and C5b-9 deposits were correlated with the severity of DN (ρ = 0.341 and 0.259, respectively; P < 0.001). Conclusion: Complement activation is correlated with both the presence and severity of DN, suggesting that the complement system is involved in the development of renal pathology in patients with diabetes and is a promising target for inhibiting and/or preventing DN in these patients.http://www.sciencedirect.com/science/article/pii/S2468024917304230C4dcomplement activationdiabetic nephropathyhistological lesionsrenal pathology
spellingShingle Pascal Bus
Jamie S. Chua
Céline Q.F. Klessens
Malu Zandbergen
Ron Wolterbeek
Cees van Kooten
Leendert A. Trouw
Jan A. Bruijn
Hans J. Baelde
Complement Activation in Patients With Diabetic Nephropathy
Kidney International Reports
C4d
complement activation
diabetic nephropathy
histological lesions
renal pathology
title Complement Activation in Patients With Diabetic Nephropathy
title_full Complement Activation in Patients With Diabetic Nephropathy
title_fullStr Complement Activation in Patients With Diabetic Nephropathy
title_full_unstemmed Complement Activation in Patients With Diabetic Nephropathy
title_short Complement Activation in Patients With Diabetic Nephropathy
title_sort complement activation in patients with diabetic nephropathy
topic C4d
complement activation
diabetic nephropathy
histological lesions
renal pathology
url http://www.sciencedirect.com/science/article/pii/S2468024917304230
work_keys_str_mv AT pascalbus complementactivationinpatientswithdiabeticnephropathy
AT jamieschua complementactivationinpatientswithdiabeticnephropathy
AT celineqfklessens complementactivationinpatientswithdiabeticnephropathy
AT maluzandbergen complementactivationinpatientswithdiabeticnephropathy
AT ronwolterbeek complementactivationinpatientswithdiabeticnephropathy
AT ceesvankooten complementactivationinpatientswithdiabeticnephropathy
AT leendertatrouw complementactivationinpatientswithdiabeticnephropathy
AT janabruijn complementactivationinpatientswithdiabeticnephropathy
AT hansjbaelde complementactivationinpatientswithdiabeticnephropathy