Tenofovir disoproxil fumarate associated nephrotoxicity: a retrospective cohort study at two referral hospitals in Namibia

Abstract

IntroductionThe incidence and risk factors of tenofovir disoproxil fumarate (TDF)‐related renal impairment (RI) in Namibia are unknown where TDF‐containing ART regimens are used as the first line for HIV.MethodologyA retrospective cohort study among HIV‐infected patients at two intermediate hospitals. A decline in estimated glomerular filtration rate (eGFR) was significant if it was ≥25% and included a change to a lower eGFR stage. New‐onset RI was defined as an eGFR <50 mL/min/1.73m2.Results10 387 patients were included: 11.4% (n = 1182) experienced the decline in eGFR. Of these, 0.6% (n = 62) migrated to eGFR stages IV and V. The incidence was 4.5 (95% CI: 4.3‐4.8) per 100 patient years. RI developed in 400 patients for an incidence rate of 2.4 (95% CI: 2.2‐2.6) cases per 100 patient years. Risk factors with effect sizes >2.0, for decline‐in‐eGFR were baseline eGFR >60 (aHR = 15.6); hyperfiltration (aHR = 5.0); and pregnancy (aHR = 2.4); while for RI, they were hyperfiltration (aHR = 4.1) and pregnancy (aHR = 29).ConclusionThe incidence of decline‐in‐eGFR was higher than in other sub‐SSA countries, but not RI. A high baseline eGFR had the greatest risk for the decline, and hyperfiltration for the RI.

Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: cross-sectional study in North-Western Tanzania

“…On the other hand, the prevalence of moderately-severely impaired renal function (eGFR < 45 mL/min/1.73m 2 ) was higher in HIVinfected adults on ART (4.8% vs. 2.8% in ART-naive HIV-infected and 1.7% in HIV-uninfected groups). These findings are in line with existing literature where modern tenofovir-based ART has been reported to improve renal function in most patients [31,32], while leading to progression of kidney disease in others [33][34][35].…”

“…Of note, as is the case in most of SSA, 46% of ARTexperienced HIV-infected participants with hyperfiltration were receiving ART regimens containing tenofovir diproxil fumarate. Tenofovir has been shown to cause renal hyperfiltration in African adults with HIV [34,35]. Renal hyperfiltration, in turn, is associated with more rapid progression of kidney disease in HIV-infected adults on tenofovir [34] as well as cardiovascular disease [36].…”

“…Tenofovir has been shown to cause renal hyperfiltration in African adults with HIV [34,35]. Renal hyperfiltration, in turn, is associated with more rapid progression of kidney disease in HIV-infected adults on tenofovir [34] as well as cardiovascular disease [36]. In long run, the overall renal benefit of HIV viral suppression in improving HIV associated nephropathy could therefore be outweighed by nephrotoxic effects of tenofovir containing ART in populations at high risk for kidney disease.…”

“…Impaired renal function was defined according to Kidney Disease Improving Global Outcome (KDIGO) guidelines [24] as eGFR < 60 mL/min/1.73m 2 . We further categorised renal function according to KDIGO guidelines as follows: normal (≥ 90), mildly decreased (60-89), mildly to moderately decreased (45-59), moderately to severely decreased (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44), severely decreased (15-29) and kidney failure (< 15). Renal hyperfiltration was defined as eGFR > 135 mL/min/1.73m 2 [25].…”

Incidence of impaired kidney function among people with HIV: a systematic review and meta-analysis

“… 2019 China Jul.2014-Apr.2015 eGFR≥60 97 258 1.2 3 CKD-EPI Dietrich L. G [ 76 ]. 2020 Switzerland Two periods with only median time eGFR≥80 81.3 3603 6.2 225 CKD-EPI Liu F [ 23 ] 2020 China Jan.2010/ Dec.2015-Jan.2017 eGFR≥90 4.6 823 54.8 451 CKD-EPI Kalemeera F [ 77 ]. 2021 Namibia Aug.2010-Dec.2016 eGFR≥60 39.6 6744 5.9 400 CKD-EPI Note: sixteen studies reported two or more definitions of IKF at same time MDRD, modification of diet in renal disease; CKD-EPI, Chronic kidney disease Epidemiology collaboration; NR: not report; D:A:D study, The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, which is conducted in Europe, USA and Australia; EuroSIDA Study, a pan-European observational study that is conducted in Europe, Israel and Argentina.…”