An estimated 4 million Americans have been exposed to the hepatitis C virus (HCV). The risks of incident and progressive chronic kidney disease and of mortality in patients with normal kidney function infected with HCV are unclear. In a nationally representative cohort of 100,518 HCV+ and 920,531 HCV- US veterans with normal baseline estimated glomerular filtration rate (eGFR), we examined the association of HCV infection with (1) all-cause mortality, (2) incidence of decreased kidney function (defined as eGFR <60 mL/min/1.73 m2 and 25% decrease in eGFR), (3) end-stage renal disease, and (4) rate of kidney function decline. Associations were examined in naive and adjusted Cox models (for time-to-event analyses) and logistic regression models (for slopes), with sequential adjustments for important confounders. Propensity-matched cohort analysis was used in sensitivity analyses. The patients' age was 54.5±13.1 (mean±standard deviation) years, 22% were black, 92% were male, and the baseline eGFR was 88±16 mL/min/1.73 m2. In multivariable adjusted models HCV infection was associated with a 2.2-fold higher mortality (fully adjusted hazard ratio=2.17, 95% confidence interval [CI] 2.13-2.21), a 15% higher incidence of decreased kidney function (adjusted hazard ratio=1.15, 95% CI 1.12-1.17), a 22% higher risk of steeper slopes of eGFR (adjusted odds ratio=1.22, 95% CI 1.19-1.26), and a 98% higher hazard of end-stage renal disease (adjusted hazard ratio=1.98, 95% CI 1.81-2.16). Quantitatively similar results were found in propensity-matched cohort analyses. Conclusions: Infection with HCV is associated with higher mortality risk, incidence of decreased kidney function, and progressive loss of kidney function; randomized controlled trials are warranted to determine whether treatment of HCV infection can prevent the development and progression of chronic kidney disease and improve patient outcomes.
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