BACKGROUND AND OBJECTIVES Hepatitis C virus (HCV) infection and kidney disease are both highly prevalent diseases. The association between HCV and GN has been supported by previous research but little is known about the relationship between HCV and kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic review of the published medical literature was conducted to determine if HCV is associated with increased likelihood of kidney disease in the general population. A random-effects model was used to generate a summary estimate of the relative risk for kidney disease, defined as an estimated GFR <60 ml/min per 1.73 m(2) or proteinuria, with HCV across the published studies. RESULTS Nine clinical studies (817,917 unique individuals) were identified. Pooling of study results demonstrated the absence of a relationship between HCV seropositive status and reduced estimated GFR (adjusted relative risk, 1.12; 95% confidence interval, 0.91, 1.38; P=0.28) according to the random-effects model. HCV seropositive serology was an independent and significant risk factor for proteinuria (defined by urine dipstick test or spot urine albumin/creatinine ratio) in the general population, with a summary estimate for adjusted relative risk of 1.47 (95% confidence interval, 1.12, 1.94; P=0.006). Significant heterogeneity was observed between studies (Ri=0.82; P value by Q test, <0.001). CONCLUSIONS This meta-analysis shows that HCV is independently associated with proteinuria but not with reduced GFR in the general population. Substantial heterogeneity occurred.