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
UR - http://www.scopus.com/inward/record.url?scp=85064633158&partnerID=8YFLogxK
U2 - 10.1111/nep.13477
DO - 10.1111/nep.13477
M3 - Journal article
C2 - 30141239
SN - 1320-5358
VL - 24
SP - 703
EP - 710
JO - Nephrology (Carlton, Vic.)
JF - Nephrology (Carlton, Vic.)
IS - 7
ER -