Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment

Abstract

BackgroundTenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear.MethodsPatients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89–60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates).Results2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2–3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8–2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4–6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF.ConclusionsPrompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage.

Reduced Kidney Function in Tenofovir Disoproxil Fumarate Based Regimen and Associated Factors: A Hospital Based Prospective Observational Study in Ethiopian Patients

“…Generally, the occurrence of renal dysfunction is becoming common in HIV infected patients who received TDF based antiretroviral regimen and its burden on survival and quality of life is becoming worse [34]. The condition of renal complication in HIV infected patients can be worst in low and middle income countries as the condition requires enough capital to manage renal complications.…”

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load

“…However, there is a need of additional data in regard to the use of RPV with other drugs, since in the trials above mentioned, few patients received RPV with the combination of abacavir/lamivudine (ABC/3TC), and it is not known if virological efficacy associated with a regimen based on RPV plus ABC/3TC might differ according to CD4+ nadir or pre-ART viral load. Indeed, these data could be useful in the current clinical management of patients, especially taking into account the well-known kidney and bone toxicity due to TDF [ 8 , 9 ].…”

Factors associated to chronic kidney disease in people living with HIV/AIDS

“…By postponing the discontinuation of nephrotoxic ARDs, transient damage to renal structures can become permanent ( 26 , 28 , 46 ) . Both the high prevalence of the use of nephrotoxic ARDs in a previous and current scheme, and the cumulative exposure of these ARDs may justify the number of cases found in this study.…”

“…As for the nephrotoxic anti-retrovirals, ARDs already proven in the literature were considered to be nephrotoxic: Tenofovir Disoproxil Fumarate (TDF) ( 26 - 28 ) , Atazanavir (ATV), Lopinavir boosted with Ritonavir (LPV/r), and Indinavir (IDV) ( 7 , 29 ) .…”