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Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.

ABSTRACT: After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Complement factor H (CFH) is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression.A total of 351 patients with IgAN participated in this study. They were followed up for an average of 51.8 ± 26.6 months. Renal outcome was defined as a composite endpoint, that included instances of end-stage renal disease (ESRD), ? 50% decline in estimated glomerular filtration rate (eGFR) or doubling of plasma creatinine levels. Urinary CFH levels were measured by enzyme-linked immunosorbent assay and calculated as the ratio of urinary CFH over creatinine (uCFH/uCr).In the whole cohort, uCFH/uCr values were associated with disease progression either as continuous [log(uCFH/uCr)] or categorical traits (dichotomous and quartile variables) after adjusting for eGFR, proteinuria, mean arterial blood pressure, histological grading and immunosuppressive therapy in the Cox proportional hazard model. Kaplan-Meier analysis showed that higher uCFH/uCr values at baseline predicted worse renal outcome during follow-up (log-rank, P < 0.001). Receiver operating characteristic curve (ROC) analysis showed that log(uCFH/uCr) had predictive value for renal outcome (area under curve [AUC] = 0.745), and the AUC increased to 0.805 after being incorporated into baseline eGFR and proteinuria. In subgroup analysis with eGFR ? 60 mL/min/1.73 m2, log(uCFH/uCr) had better predictive value (AUC = 0.724, P = 0.002) for renal outcome compared to eGFR (AUC = 0.582, P = 0.259) and proteinuria (AUC = 0.615, P = 0.114).Urinary CFH levels are associated with renal function decline and increased urinary CFH levels are a risk factor for progression of IgA nephropathy.

SUBMITTER: Liu M

PROVIDER: S-EPMC4452759 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.

Liu Maojing M Chen Yuqing Y Zhou Jingjing J Liu Ying Y Wang Fengmei F Shi Sufang S Zhao Yanfeng Y Wang Suxia S Liu Lijun L Lv Jicheng J Zhang Hong H Zhao Minghui M

PloS one 20150602 6

<h4>Background</h4>After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Complement factor H (CFH) is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression.<h4>Methods</h4>A total of 351 patients with IgAN participated in this study. They were followed up for an average of 51.8 ± 26.6 months. Renal outcome was defined as a composite end ...[more]

PMID: 26035554

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Project description:BackgroundDisorders of calcium and phosphorus metabolism have been reported to be associated with all-cause and cardiovascular mortality in patients requiring long-term dialysis therapy. However, its role in disease progression is not well established in patients without dialysis, especially in immunoglobulin A (IgA) nephropathy. We aim to evaluate the association of serum phosphorus and calcium and progression of IgA nephropathy.MethodsWe assessed 2567 patients with IgA nephropathy at the First Affiliated Hospital, College of Medicine, Zhejiang University. Serum phosphorus and calcium were collected at the time of kidney biopsy and at each visit. The associations of serum phosphorus and serum calcium with composite kidney disease progression events, defined as 50% estimated glomerular filtration rate (eGFR) decline and kidney failure, were examined using Cox models and restricted cubic splines.ResultsDuring a median follow-up of 31.9 months, 248 (10%) patients reached composite kidney disease progression events. A linear relationship was observed between serum phosphorus and composite kidney disease progression events. With higher levels of phosphorus, the risk of kidney disease progression events increased {hazard ratio [HR] 3.54 [95% confidence interval (CI) 1.37-9.12]; P = 0.009}. Compared with the first quartile group, the HR of kidney disease progression events was 1.66 (95% CI 0.91-301) for the second quartile, 1.67 (95% CI 0.91-3.08) for the third and 2.62 (95% CI 1.44-4.77) for the fourth (P for trend = 0.002). The association between serum phosphorus and kidney disease progression was detectable [HR 8.94 (95% CI 2.33-34.21); P = 0.001] within the subgroup with eGFR <60 mL/min/1.73 m2 but not among patients with eGFR ≥60 mL/min/1.73 m2 [HR 0.87 (95% CI 0.17-4.44); P = 0.87]. After adjustment for traditional risk factors, a higher level of serum calcium was not associated with kidney disease progression events [HR 0.33 (95% CI 0.10-1.09)].ConclusionsHigher serum phosphorus rather than serum calcium was independently associated with kidney disease progression in IgA nephropathy.

Dataset Information

Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.

Publications

Implication of urinary complement factor H in the progression of immunoglobulin A nephropathy.

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