Changes in estimated glomerular filtration rate over time in South African HIV‐1‐infected patients receiving tenofovir: a retrospective cohort study

Abstract

Introduction: Tenofovir has been associated with decline in kidney function, but in patients with low baseline kidney function, improvements over time have been reported. Additionally, the magnitude and trajectory of estimated glomerular filtration rate (eGFR) changes may differ according to how eGFR is calculated. We described changes in eGFR over time, and the incidence of, and risk factors for, kidney toxicity, in a South African cohort.Methods: We included antiretroviral-naïve patients ≥16 years old who started tenofovir-containing antiretroviral therapy (ART) between 2002 and 2013. We calculated eGFR using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault equations. We described changes in eGFR from ART initiation using linear mixed effects regression. We described the incidence of eGFR <30 mL/min on treatment, and identified associations with low eGFR using Cox regression.Results: We included 15156 patients with median age of 35.4 years (IQR 29.9–42.0), median CD4 cell count of 168 cells/µL (IQR 83–243), and median eGFR (MDRD) of 98.6 mL/min (IQR 84.4–115.6). Median duration of follow up on tenofovir was 12.9 months (IQR 5.1–23.3).Amongst those with a baseline and subsequent eGFR available, mean eGFR change from baseline at 12 months was −4.4 mL/min (95% CI −4.9 to −4.0), −2.3 (−2.5 to −2.1), and 0.6 (0.04 to 1.2) in those with baseline eGFR ≥90 mL/min; and 11.9 mL/min (11.0 to 12.7), 14.6 (13.5 to 15.7), and 11.0 (10.3 to 11.7) in those with baseline eGFR <90 mL/min, according to the MDRD, CKD-EPI (n = 11 112), and Cockcroft-Gault (n = 9 283) equations, respectively.Overall, 292 (1.9%) patients developed eGFR <30 mL/min. Significant associations with low eGFR included older age, baseline eGFR <60 mL/min, CD4 count <200 cells/µL, body weight <60 kg, and concomitant protease inhibitor use.Conclusions: Patients on tenofovir with baseline eGFR ≥90 mL/min experienced small but significant declines in eGFR over time when eGFR was estimated using the MDRD or CKD-EPI equations. However, eGFR increased in patients with eGFR <90 mL/min, regardless of which estimating equation was used. Decreases to below 30 mL/min were uncommon. In settings with limited access to laboratory testing, monitoring guidelines should consider focusing on higher risk patients.

Renal dysfunction by baseline CD4 cell count in a cohort of adults starting antiretroviral treatment regardless of CD4 count in the HIV Prevention Trials Network 071 [HPTN 071; Population Effect of Antiretroviral Therapy to Reduce HIV Transmission (PopART)] study in South Africa

“…This study found a low baseline prevalence rate of eGFR < 60 mL/min (1.9%), similar to that in a large published study from Zambia . Also similar to previous studies , this study showed lower baseline prevalence of renal dysfunction at baseline CD4 counts > 200 cells/μL and among younger individuals.…”

“…This is one of the first studies to evaluate the association between baseline CD4 count and renal dysfunction in the context of routine provision of ART regardless of CD4 count in a high‐burden programmatic setting. Probably as a result of this expanded ART access, the baseline median CD4 count in this study (328 cells/μL) was higher than that reported in previous studies from high‐burden settings . This study found a low baseline prevalence rate of eGFR < 60 mL/min (1.9%), similar to that in a large published study from Zambia .…”

“…eGFR was calculated from SCR, age and sex using the Modification of Diet in Renal Disease Study (MDRD) Study equation [eGFR = 175 × standardized SCR −1.154 × age −0.203 × 1.212 (if black) × 0.742 (if female)] , with omission of the racial category factor. This method for estimating eGFR from serum creatinine has been previously validated in the South African context and shown to be more accurate than the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations . MDRD is the method of choice for estimating eGFR from results of the current serum creatinine assay used by the NHLS in South Africa and at the clinics included in this study .…”

“…An association has been reported between low CD4 count and renal dysfunction after ART initiation, from programmatic studies, with median baseline CD4 counts ranging from 154 to 209 cells/μL. These studies reported less renal dysfunction following ART initiation among individuals with baseline CD4 counts > 200 cells/μL compared with lower values . Recently published results from the Strategic timing of antiretroviral treatment (START) trial showed higher mean eGFR after ART initiation among individuals starting ART at baseline CD4 counts > 500 cells/μL compared with those with baseline CD4 counts of 350–500 cells/μL .…”

Effects of aging, baseline renal function and stage of HIV infection on post‐treatment changes in renal function among HIV‐infected patients: a retrospective cohort study

“…Previous studies have shown that changes in renal function differ by the level of baseline renal function, with improvement in patients with baseline renal impairment but deterioration in patients with baseline normal renal function . Studies have also shown that cART could improve renal function among patients with advanced HIV stage at baseline .…”