Cleared HCV infection associated with increased risk of kidney disease in people with HIV

People living with HIV with previous hepatitis C virus (HCV) infection continue to have an increased risk of chronic kidney disease, results of a North American study published in the online edition of the Journal of Infectious Diseases show.

The incidence of serious chronic kidney disease was similarly elevated for people who had cleared HCV infection and those with ongoing HCV viral replication. Both groups also had a similar risk of experiencing kidney disease progression.

“Unexpectedly, we found that prior HCV infection was associated with excess CKD [chronic kidney disease] risk irrespective of the presence or absence of HCV viremia [detectable viral load],” comment the authors. “Our results suggest that chronic HCV viremia is not the primary factor mediating increased CKD risk in HIV-infected persons with prior HCV exposure.”

Between a quarter and a third of people living with HIV in the United States also have HCV (co-infection). Epidemiological data suggest that infection with HCV is linked to an increased risk of chronic kidney disease and renal failure in both the general population and individuals with HIV.

A proportion of people spontaneously clear HCV infection and HCV can also be cured with antiviral treatment. A team of investigators from the United States and Canada wanted to explore the association between chronic HCV infection – ongoing HCV replication – and the risk of chronic kidney disease.

They therefore compared the incidence of kidney disease in a cohort of 63,000 people according to HCV exposure status: negative for HCV antibodies (HCV uninfected); ongoing HCV replication (viraemic); antibodies to HCV but no detectable HCV viral load (aviraemic).

Estimated glomerular filtration rate (eGFR) was used as a marker of chronic kidney disease. People with eGFR below 60/ml/min/1.73m² were defined as having moderate kidney disease; eGFR below 15/ml/min/1.73m² was defined as severe kidney disease; and progressive kidney disease was defined as a 25% reduction in eGFR from a baseline above 60/ml/min/1.73m² lasting 60 or more days.

All the study participants received care after 1996. Most – 52,602 – had never been infected with HCV; 9508 were HCV viraemic; and 913 had antibodies to HCV but no viral replication.

The participants had a median age of 42 years and 41% were black. Just over a third (35%) had a suppressed HIV viral load and the median CD4 cell count was 340 cells/mm³.

There was a high prevalence of risk factors known to be associated with chronic kidney disease. Overall, a quarter of participants had hypertension (high blood pressure), 5% were diabetic and approximately a fifth had a history of injecting drug use. The authors controlled for these factors in their statistical analysis.

Compared to people who had never had HCV, individuals with ongoing HCV replication had an increased risk of moderate chronic kidney disease (adjusted HR, 1.36; 95%, 1.26-1.46), serious chronic kidney disease (adjusted HR, 1.95; 95% CI, 1.64-2.31) and progressive renal disease (adjusted HR, 1.31; 95% CI, 1.19-1.44).

People with antibodies to HCV but no viral replication were also more likely to develop serious renal disease compared to HCV-negative people. There was an association of borderline significance between past HCV infection and progression to moderate chronic kidney disease (adjusted HR, 1.19; 95% CI, 0.98-1.45), and significant associations with progression to serious chronic renal disease (adjusted HR, 1.69; 95% CI, 1.07-2.65) and progressive chronic kidney disease (adjusted HR, 1.31; 95% CI, 1.02-1.68).

Comparison between the HCV-viraemic and -aviraemic participants in the study showed that both groups had a similar risk of each of the three study outcomes.

The association between current and past HCV infection and the progression of chronic kidney disease remained robust in a series of sensitivity analyses.

“We found that HIV-infected individuals with prior HCV co-infection were at risk for moderate and advanced CKD, regardless of the presence of HCV viremia,” conclude the authors. “The mechanism behind CKD risk in aviremic subjects is unclear, but may include confounding effects from drug use, poorer control of HIV infection, lower socioeconomic status, or other unidentified factors.”