Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy.
OBJECTIVE
Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN.


METHODS
A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr).


RESULTS
Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04).


CONCLUSIONS
This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Seung Jun
SJ
Kim
Hyang Mo
HM
Koo
Beom Jin
BJ
Lim
Hyung Jung
HJ
Oh
Dong Eun
DE
Yoo
Dong Ho
DH
Shin
Mi Jung
MJ
Lee
Fa Mee
FM
Doh
Jung Tak
JT
Park
Tae-Hyun
TH
Yoo
Shin-Wook
SW
Kang
Kyu Hun
KH
Choi
Hyeon Joo
HJ
Jeong
Seung Hyeok
SH
Han
D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology*; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D055815:Young Adult
D003176:Complement C3; D003404:Creatinine