Hepatitis C Infection with HIV Raises Risk of Chronic Kidney Disease

Chronic hepatitis C virus (HCV) infection raises the risk for chronic kidney disease (CKD) in people infected with human immunodeficiency virus (HIV). Clearing the HCV infection appears to reverse this effect, researchers have found.

“In this whole era of treatability of HIV [and] the aging patient, it becomes of much bigger concern what other target organ damage are we going to see,” Jürgen Rockstroh, MD, told ASN Kidney News at the 13th European AIDS Conference in Belgrade, Serbia, late last year. Rockstroh is professor of medicine and head of the HIV clinic in the department of medicine at the University of Bonn in Bonn, Germany.

“In several observations we’ve seen there has been an independent association between hepatitis C co-infection and risk for development of chronic kidney disease,” Rockstroh said.

In the United States, about 25 percent of individuals infected with HIV are also infected with HCV. The rate among injection drug users is much higher. About 80 percent of users with HIV are also infected with HCV, according to the U.S. Centers for Disease Control and Prevention.

Using the prospective, observational EuroSIDA international cohort of more than 16,500 HIV-infected patients, investigators found that when compared to HIV-infected people who were negative for HCV antibodies, individuals who were positive for HCV antibodies had a 98 percent increased incidence of CKD.

HCV antibodies indicate exposure to the virus at some point and may persist even if the virus is cleared from the body naturally or by treatment. Viremia, or circulating HCV RNA, indicates an active infection.

Patients eligible for the study had at least three serum creatinine determinations after January 1, 2004. Their HCV antibody status was known. The baseline estimated glomerular filtration rate (eGFR) was the first one recorded, and CKD was defined either as an eGFR less than or equal to 60 mL/min/1.73 m2 for individuals with baselines above this point, or as a 25 percent decline in eGFR for individuals whose baseline was at or below 60 mL/min/1.73 m2.

Among 8001 patients, 1964 (24.5 percent) were positive for HCV antibodies. Of these, 972 (49.5 percent) were HCV RNA-positive. At baseline, the median age was 41 years, the median CD4 T cell count was 439 cells/mm3 (range 294–627), and the median eGFR was 97.6 mL/min/1.73 m2 (range 83.8–113.0). Progression to CKD occurred in 410 patients (5.1 percent)—an incidence of 13.6 per 1000 person-years of follow up. For those who progressed to CKD these variables were accounted for: cumulative use of nephrotoxic drugs and antiretroviral drugs, CD4 counts and nadirs, age, gender, and diabetes.

Patients with HCV antibodies who had HCV viremia or had unknown HCV RNA status in their blood were at significantly higher risk for CKD. The higher the viral load, the higher the incidence of CKD (p< 0.04 for all viral loads greater than 615 IU/mL).

Individuals with antibodies but who had undetectable viral loads (<615 IU/mL) were at no greater risk for CKD compared to patients without HCV antibodies. The incidence of CKD was not associated with the HCV viral genotype.

Rockstroh said it is not known why patients with HCV are at higher risk for the development of CKD.

“One point could be that patients who have chronic hepatitis C obviously will have different stages of liver disease, and in very end stage liver disease you can often have what we call hepatorenal syndrome, so there are perfusion issues with the kidney, and then you can get kidney failure,” he speculated. Another contributing factor could be altered drug metabolism by the liver, leading to levels of antiretroviral drugs that may cause renal tubular damage.

A remaining question is whether successful treatment and clearance of HCV can reverse kidney disease. The EuroSIDA database probably has too few successfully treated patients to answer the question since many come from Eastern Europe, where treatment is often not available.

At this point, Rockstroh recommends careful selection of any renal toxic antiretroviral drugs. Beyond that, “we just have to monitor renal function and renal disease parameters more closely in [HIV] patients with hepatitis C in the future,” he said.