Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B.

BACKGROUND & AIMS: Therapy of chronic hepatitis B with HBV-polymerase inhibitors, in particular tenofovir or adefovir, may affect renal function. To assess renal function more accurately in the normal range, we used the recently validated, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate the estimated glomerular filtration rate (eGFR). METHODS: Patient subgroups included: patients with HBV-monoinfection treated with lamivudine (n=36), adefovir (n=32), entecavir (n=32), or tenofovir (n=37). HBsAg-positive untreated patients (n=60) served as control. For comparison HIV-monoinfected patients treated with tenofovir (n=120) or zidovudine (n=52) based antiretroviral therapy and antiretroviral naive patients (n=109) were assessed. CKD-EPI equation was used to calculate eGFR. In a more sensitive approach, we modeled the individual change in eGFR over time with linear mixed effects models (LME). RESULTS: Yearly predicted median changes in individual eGFR according to the LME model were: HBV untreated -2.05 ml/min, HBV lamivudine -0.92 ml/min, HBV adefovir -1.02 ml/min, HBV entecavir -1.00 ml/min, and HBV tenofovir -0.92 ml/min (p<0.01 for HBV untreated vs. HBV treated). In HIV-monoinfected patients: HIV untreated -0.62 ml/min, HIV treated with tenofovir -2.64 ml/min, HIV treated with zidovudine -1.0 ml/min (p=0.017 for tenofovir vs. no treatment, p<0.001 for tenofovir vs. zidovudine). CONCLUSIONS: Therapy of HBV infection irrespective of medication seems to result in a milder decrease of renal function. In contrast tenofovir as part of HIV combination therapy seems to impair renal function in this Caucasian population.

Cystatin C as a marker of renal function is affected by HIV replication leading to an underestimation of kidney function in HIV patients.

BACKGROUND: Broad use of tenofovir and an ageing HIV- infected population have created an interest in renal function in HIV patients. Serum cystatin C is a newer marker of renal function and might be more sensitive than creatinine. METHODS: Patients were enrolled consecutively in an observational study. HIV-seropositive patients naive to antiretroviral therapy (n = 261) were compared with healthy volunteers undergoing check-up procedures (n = 193). Estimated glomerular filtration rate (eGFR) was derived using creatinine-based Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formulas or cystatin C-based calculations. HIV-seropositive patients starting antiretroviral therapy (n = 92) were followed prospectively after enrolment. RESULTS: MDRD showed a higher median eGFR in antiretroviral-naive HIV-seropositive patients compared with controls (104 versus 93 ml/min; P < 0.001). Cockcroft-Gault gave similar results (118 versus 106 ml/min; P < 0.001). By contrast, cystatin C levels in HIV-seropositive individuals were higher, resulting in a lower median eGFR compared with controls (99 versus 120 ml/min; P < 0.001). Cystatin C was positively correlated with HIV RNA (r = 0.33, P < 0.01) and inversely correlated with CD4+ T-cell count (r = -0.29, P < 0.01). Initiating antiretroviral therapy (n = 92) decreased cystatin C levels and led to an increased cystatin C-based eGFR from median 84 to 103 ml/min at week 24 (P < 0.001). Serum creatinine was not substantially altered. CONCLUSIONS: Correlation of cystatin C with HIV RNA and CD4+ T-cell count, plus decrease of cystatin C after suppression of HIV replication, suggest an increase of cystatin C levels by active HIV infection. This might result in overestimation of renal impairment, particularly in treatment-naive patients. Therefore, use of cystatin C to calculate GFR in HIV-seropositive individuals should not be recommended without further validation.