Tenofovir alafenamide nephrotoxicity in an HIV-positive patient

Abstract

This case suggests that at risk individuals may experience tubular mitochondrial injury from lower concentrations of tenofovir with TAF.

Clinical Pharmacology in HIV Therapy

“…Similar observations were made in experienced patients in switch studies, where TAF replaced TDF (38). Despite the favorable kidney safety indicators from large clinical trials, TAF may potentially be nephrotoxic in persons with comorbid conditions, such as chronic liver disease and diabetes mellitus, as recently reported (29). Consequently, longitudinal follow-up studies will be required to ascertain the nephrotoxicity potential, if any, of TAF and its beneficial effect over TDF (39).…”

“…However, it is the proximal tubular eosinophilic inclusions representing giant mitochondria that are considered distinctive features seen with tenofovir nephrotoxicity (27). By electron microscopy, these changes in proximal tubular cells mitochondria architecture characteristic of tenofovir nephrotoxicity can also be recognized, including autophagosomes and dysmorphic mitochondria of variable sizes, shapes, and incomplete cristae (27,29). Use of TDF with PIs, such as atazanavir or ritonavir, increases TDF drug concentrations and boosts its potential for nephrotoxicity and incident CKD (8).…”

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

“…While these data suggest that there were no immediate demonstrable adverse effects of TAF on kidney function, longer term safety data are required to confirm the safety of TAF in this vulnerable group of patients, and hence this study will continue to follow all participants until at least 96 weeks. Clinical trial data suggest that TAF may be a suitable option for people with HIV infection who have mild-tomoderate CKD, [11] and, while some case reports suggest that TAF may also be an option for those who experienced treatment-limiting PRT on TDF, [12][13][14][15] others have reported acute kidney injury (AKI) with and without tubular function abnormalities in selected individuals receiving TAF [19][20][21][22]. While these cases raise the possibility of TAF nephrotoxicity, in one case the patient took an overdose (300 mg of TAF among other compounds); the second patient had liver cirrhosis and diabetes, actively used heroin and cocaine, had multiple co-medications and presented with AKI and nephrotic syndrome; the third patient had decompensated liver cirrhosis, actively used alcohol, underwent treatment for hepatitis and also presented with AKI and nephrotic syndrome; and the fourth patient presented with AKI shortly after switching from TDF, which he had tolerated for the past 10 years, each suggesting that other factors could have contributed to and/or were responsible for the kidney injury.…”

Acute Kidney Injury in a Patient on Tenofovir Alafenamide Fumarate After Initiation of Treatment for Hepatitis C Virus Infection

“…Novick and colleagues published a report of a patient with HIV/HCV on an HIV regimen containing both TAF and cobicistat who developed AKI [ 15 ]. Renal biopsy showed mitrochondrial abnormalities consistent with the histologic pattern of tenofovir-induced nephrotoxicity.…”