Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR <60 mL/min/1.73 m2 or 25% decline with a baseline <60). Generalized Estimating Equations were used to model the odds of progressive CKD.
At baseline, 13.8% and 3.3% of participants were co-infected with HCV and HBV, respectively. Median eGFR was 111, and 3.7% developed progressive CKD. After adjustment, the odds of progressive CKD were increased in participants with HCV (OR 1.72, 95% CI 1.07–2.76) or HBV (OR 2.26, 95% CI 1.15–4.44). Participants with undetectable or low HCV-RNA had similar odds of progressive CKD as HCV seronegative participants, while participants with HCV-RNA >800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60–5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD.
ClinicalTrials.gov NCT00027352; NCT00004978
In 2006, ten years after the widespread introduction of effective combination antiretroviral therapy (cART) for the treatment of human immunodeficiency virus (HIV) infection, the randomized Strategies for Management of Antiretroviral Therapy trial (SMART) established uninterrupted cART with the goal of continuous viral suppression as the standard of care.  Although the primary outcome of SMART focused on mortality and opportunistic illness associated with acquired immunodeficiency syndrome (AIDS), the results also highlighted the growing burden of comorbid disease in the cART era. During an average follow-up of 16 months, serious cardiac, liver, and kidney events were more common than serious AIDS-defining events, regardless of treatment assignment. .
Chronic kidney disease (CKD) has been associated with increased morbidity and mortality in HIV-positive individuals receiving cART. – In addition to traditional CKD risk factors such as diabetes and hypertension, co-infection with hepatitis C virus (HCV) has been suggested as a possible risk factor for CKD in HIV-positive individuals.  Although there are conflicting data on the relationship between HCV infection and CKD in the general population, meta-analysis of published studies in HIV-positive populations supports an association between HIV-HCV co-infection and increased risk of CKD.  The relationship between hepatitis B virus (HBV) infection and CKD has not been as extensively studied, although cross-sectional studies have not demonstrated an association between HBV mono-infection and prevalent CKD. –.
Both HBV and HCV have been implicated in the pathogenesis of specific immune complex kidney diseases in the general population and in HIV-positive individuals,– and clinically silent immune complex kidney disease has been observed in HCV mono-infected patients with end-stage liver disease.  End-stage liver disease has also been associated with increased risk of overt CKD in HCV-infected individuals, although data on the relative contribution of immune complex disease and hepatorenal syndrome were not available.  Previous studies have not investigated other potential mediators of the relationship between viral hepatitis and CKD, including earlier stages of hepatic fibrosis and liver dysfunction, increased levels of systemic inflammation, or nephrotoxic effects of antiviral therapy for HBV or HCV. In addition, the majority of prior studies defined viral hepatitis co-infection by serology alone, and did not report data on HBV DNA, HCV RNA, or HCV genotype as potential mediators or effectors of the relationship between viral hepatitis and CKD.
We evaluated the association between viral hepatitis co-infection and progressive CKD among 3,441 cART-treated participants enrolled in two large international HIV treatment trials, with the goal of identifying potential mediators of the relationship.