High levels of urinary complement proteins are associated with chronic renal damage and proximal tubule dysfunction in immunoglobulin A nephropathy

Lu Wen, Zhanzheng Zhao, Zheng Wang, Jing Xiao, Henrik Birn, Jon Waarst Gregersen

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Abstract

Aim: Complement activation is involved in the pathogenesis and progression of immunoglobulin A nephropathy (IgAN); however, the clinical implication of abnormal complement protein levels in serum and urine is not clear. To address this we analyzed the correlation between disease activity and complement proteins in serum and urine from IgAN patients, and compared to patients with other types of chronic kidney disease (CKD) as well as healthy controls. Methods: We included 85 Chinese patients with IgAN, 23 patients with non-proliferative CKD, and 20 healthy individuals. Patients were divided according to the Oxford classification of M0E0S0T0 (group 1, n = 20), M1E1S0-1 T0-1 (group 2, n = 25), M1E1S0-1 T2 or M0E0S1T1-2 (group 3, n = 40). Complement factor H (CFH), mannose-binding lectin and membrane attack complex in serum and urine were measured by enzyme-linked immunosorbent assay. Results: Urinary CFH, membrane attack complex and serum CFH were increased in both IgAN and CKD patients compared with healthy controls. The urinary excretion of CFH was the highest in IgAN patients with most tubulointerstitial damage (IgAN group 3). Urinary CFH and mannose-binding lectin levels were significantly higher in IgAN patients with crescents formation (C1–2) than in patients without (C0). Urinary complement protein excretion correlated negatively with estimated glomerular filtration rate, and positively with urinary retinol-binding protein and α1-microglobulin excretion indicating proximal tubule dysfunction. Conclusion: Increased urinary excretion of complement proteins in IgAN is related to chronic injury and tubular dysfunction. This warrants caution using urinary complement proteins as markers of disease activity.

Original languageEnglish
JournalNephrology (Carlton, Vic.)
Volume24
Issue number7
Pages (from-to)703-710
Number of pages8
ISSN1320-5358
DOIs
Publication statusPublished - 1 Jul 2019

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IGA Glomerulonephritis
Proximal Kidney Tubule
Complement System Proteins
Complement Factor H
Chronic Renal Insufficiency
Mannose-Binding Lectin
Complement Membrane Attack Complex
Urine
Serum
Cellular Retinol-Binding Proteins
Complement Activation
Glomerular Filtration Rate
Enzyme-Linked Immunosorbent Assay

Bibliographical note

© 2018 Asian Pacific Society of Nephrology.

Keywords

  • chronic kidney disease
  • complement proteins
  • immunoglobulin A nephropathy
  • proximal tubule dysfunction
  • urinary

Cite this

@article{3307c404a2574960aa6c919f0b9cea71,
title = "High levels of urinary complement proteins are associated with chronic renal damage and proximal tubule dysfunction in immunoglobulin A nephropathy",
abstract = "Aim: Complement activation is involved in the pathogenesis and progression of immunoglobulin A nephropathy (IgAN); however, the clinical implication of abnormal complement protein levels in serum and urine is not clear. To address this we analyzed the correlation between disease activity and complement proteins in serum and urine from IgAN patients, and compared to patients with other types of chronic kidney disease (CKD) as well as healthy controls. Methods: We included 85 Chinese patients with IgAN, 23 patients with non-proliferative CKD, and 20 healthy individuals. Patients were divided according to the Oxford classification of M0E0S0T0 (group 1, n = 20), M1E1S0-1 T0-1 (group 2, n = 25), M1E1S0-1 T2 or M0E0S1T1-2 (group 3, n = 40). Complement factor H (CFH), mannose-binding lectin and membrane attack complex in serum and urine were measured by enzyme-linked immunosorbent assay. Results: Urinary CFH, membrane attack complex and serum CFH were increased in both IgAN and CKD patients compared with healthy controls. The urinary excretion of CFH was the highest in IgAN patients with most tubulointerstitial damage (IgAN group 3). Urinary CFH and mannose-binding lectin levels were significantly higher in IgAN patients with crescents formation (C1–2) than in patients without (C0). Urinary complement protein excretion correlated negatively with estimated glomerular filtration rate, and positively with urinary retinol-binding protein and α1-microglobulin excretion indicating proximal tubule dysfunction. Conclusion: Increased urinary excretion of complement proteins in IgAN is related to chronic injury and tubular dysfunction. This warrants caution using urinary complement proteins as markers of disease activity.",
keywords = "chronic kidney disease, complement proteins, immunoglobulin A nephropathy, proximal tubule dysfunction, urinary",
author = "Lu Wen and Zhanzheng Zhao and Zheng Wang and Jing Xiao and Henrik Birn and Gregersen, {Jon Waarst}",
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High levels of urinary complement proteins are associated with chronic renal damage and proximal tubule dysfunction in immunoglobulin A nephropathy. / Wen, Lu; Zhao, Zhanzheng; Wang, Zheng; Xiao, Jing; Birn, Henrik; Gregersen, Jon Waarst.

In: Nephrology (Carlton, Vic.), Vol. 24, No. 7, 01.07.2019, p. 703-710.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - High levels of urinary complement proteins are associated with chronic renal damage and proximal tubule dysfunction in immunoglobulin A nephropathy

AU - Wen, Lu

AU - Zhao, Zhanzheng

AU - Wang, Zheng

AU - Xiao, Jing

AU - Birn, Henrik

AU - Gregersen, Jon Waarst

N1 - © 2018 Asian Pacific Society of Nephrology.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Aim: Complement activation is involved in the pathogenesis and progression of immunoglobulin A nephropathy (IgAN); however, the clinical implication of abnormal complement protein levels in serum and urine is not clear. To address this we analyzed the correlation between disease activity and complement proteins in serum and urine from IgAN patients, and compared to patients with other types of chronic kidney disease (CKD) as well as healthy controls. Methods: We included 85 Chinese patients with IgAN, 23 patients with non-proliferative CKD, and 20 healthy individuals. Patients were divided according to the Oxford classification of M0E0S0T0 (group 1, n = 20), M1E1S0-1 T0-1 (group 2, n = 25), M1E1S0-1 T2 or M0E0S1T1-2 (group 3, n = 40). Complement factor H (CFH), mannose-binding lectin and membrane attack complex in serum and urine were measured by enzyme-linked immunosorbent assay. Results: Urinary CFH, membrane attack complex and serum CFH were increased in both IgAN and CKD patients compared with healthy controls. The urinary excretion of CFH was the highest in IgAN patients with most tubulointerstitial damage (IgAN group 3). Urinary CFH and mannose-binding lectin levels were significantly higher in IgAN patients with crescents formation (C1–2) than in patients without (C0). Urinary complement protein excretion correlated negatively with estimated glomerular filtration rate, and positively with urinary retinol-binding protein and α1-microglobulin excretion indicating proximal tubule dysfunction. Conclusion: Increased urinary excretion of complement proteins in IgAN is related to chronic injury and tubular dysfunction. This warrants caution using urinary complement proteins as markers of disease activity.

AB - Aim: Complement activation is involved in the pathogenesis and progression of immunoglobulin A nephropathy (IgAN); however, the clinical implication of abnormal complement protein levels in serum and urine is not clear. To address this we analyzed the correlation between disease activity and complement proteins in serum and urine from IgAN patients, and compared to patients with other types of chronic kidney disease (CKD) as well as healthy controls. Methods: We included 85 Chinese patients with IgAN, 23 patients with non-proliferative CKD, and 20 healthy individuals. Patients were divided according to the Oxford classification of M0E0S0T0 (group 1, n = 20), M1E1S0-1 T0-1 (group 2, n = 25), M1E1S0-1 T2 or M0E0S1T1-2 (group 3, n = 40). Complement factor H (CFH), mannose-binding lectin and membrane attack complex in serum and urine were measured by enzyme-linked immunosorbent assay. Results: Urinary CFH, membrane attack complex and serum CFH were increased in both IgAN and CKD patients compared with healthy controls. The urinary excretion of CFH was the highest in IgAN patients with most tubulointerstitial damage (IgAN group 3). Urinary CFH and mannose-binding lectin levels were significantly higher in IgAN patients with crescents formation (C1–2) than in patients without (C0). Urinary complement protein excretion correlated negatively with estimated glomerular filtration rate, and positively with urinary retinol-binding protein and α1-microglobulin excretion indicating proximal tubule dysfunction. Conclusion: Increased urinary excretion of complement proteins in IgAN is related to chronic injury and tubular dysfunction. This warrants caution using urinary complement proteins as markers of disease activity.

KW - chronic kidney disease

KW - complement proteins

KW - immunoglobulin A nephropathy

KW - proximal tubule dysfunction

KW - urinary

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U2 - 10.1111/nep.13477

DO - 10.1111/nep.13477

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EP - 710

JO - Nephrology

JF - Nephrology

SN - 1320-5358

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