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Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy

Authors
 Seung Jun Kim  ;  Hyang Mo Koo  ;  Beom Jin Lim  ;  Hyung Jung Oh  ;  Dong Eun Yoo  ;  Dong Ho Shin  ;  Mi Jung Lee  ;  Fa Mee Doh  ;  Jung Tak Park  ;  Tae-Hyun Yoo  ;  Shin-Wook Kang  ;  Kyu Hun Choi  ;  Hyeon Joo Jeong  ;  Seung Hyeok Han 
Citation
 PLOS ONE, Vol.7(7) : e40495, 2012 
Journal Title
PLOS ONE
Issue Date
2012
MeSH
Adult ; Biopsy ; Cohort Studies ; Complement C3/immunology ; Complement C3/metabolism* ; Creatinine/blood ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerular Mesangium/immunology ; Glomerular Mesangium/pathology* ; Glomerulonephritis, IGA/etiology* ; Glomerulonephritis, IGA/mortality ; Glomerulonephritis, IGA/pathology* ; Humans ; Male ; Middle Aged ; Prognosis ; ROC Curve ; Risk Factors ; Young Adult
Keywords
Adult ; Biopsy ; Cohort Studies ; Complement C3/immunology ; Complement C3/metabolism* ; Creatinine/blood ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerular Mesangium/immunology ; Glomerular Mesangium/pathology* ; Glomerulonephritis, IGA/etiology* ; Glomerulonephritis, IGA/mortality ; Glomerulonephritis, IGA/pathology* ; Humans ; Male ; Middle Aged ; Prognosis ; ROC Curve ; Risk Factors ; Young Adult
Abstract
BACKGROUND AND AIMS: 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.
Files in This Item:
T201202668.pdf Download
DOI
10.1371/journal.pone.0040495
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Koo, Hyang Mo(구향모)
Kim, Seung Jun(김승준)
Doh, Fa Mee(도화미) ORCID logo https://orcid.org/0000-0002-4780-6728
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Oh, Hyung Jung(오형중)
Yoo, Dong Eun(유동은)
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Mi Jung(이미정)
Lim, Beom Jin(임범진) ORCID logo https://orcid.org/0000-0003-2856-0133
Jeong, Hyeon Joo(정현주) ORCID logo https://orcid.org/0000-0002-9695-1227
Choi, Kyu Hun(최규헌) ORCID logo https://orcid.org/0000-0003-0095-9011
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91702
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