Renal proximal tubulopathy in an HIV-infected patient treated with tenofovir alafenamide and gentamicin: a case report

Abstract

Background: The nucleotide reverse transcriptase inhibitor Tenofovir Alafenamide (TAF) is a novel pro-drug of tenofovir (TFV) and possesses a superior renal safety profile compared with tenofovir disoproxil fumerate (TDF). Due to unique pharmacokinetic characteristics, treatment with TAF is not associated with significant renal proximal tubular accumulation of TFV. TAF is associated with a lower risk of acute kidney injury, chronic kidney disease, proteinuria and renal proximal tubular dysfunction than treatment with TDF. No cases of Fanconi syndrome have been reported in clinical trials of TAF. It is unknown whether treatment with TAF can lead to accumulation of TFV in proximal tubular cells and cause nephrotoxicity under certain clinical circumstances. Case presentation: Here we report the case of a patient on stable TAF-based antiretroviral therapy with for HIV-1 infection who developed proximal tubulopathy when treated with gentamicin for febrile neutropenia in the context of relapsed Hodgkin lymphoma. Eighteen days after commencing chemotherapy for relapsed Hodgkin lymphoma the patient presented to hospital with fevers, hypotension and neutropenia. The patient was commenced on piperacillin, tazobactam and gentamicin. Within 24 h the patient developed marked hypokalaemia and hypophosphataemia requiring intravenous replacement therapy. There was proteinuria, glycosuria and evidence of marked urinary electrolyte wasting, consistent with acute proximal tubular dysfunction. Eleven days after the gentamicin was stopped the serum biochemistry normalised. The urinary electrolyte wasting and proteinuria had improved, and the glycosuria had resolved. Conclusion: This is the first case report to describe acute renal proximal tubulopathy in an HIV-infected patient treated with TAF and gentamicin. As the number of patients prescribed TAF outside the clinical trial setting increases, so too does the potential for previously unreported drug interactions and adverse events. Clinicians need to be aware of potential unreported adverse drug reactions as the use of TAF becomes increasingly common in clinical practice.

Safety of Tenofovir Alafenamide in People With HIV Who Experienced Proximal Renal Tubulopathy on Tenofovir Disoproxil Fumarate

“…Kidney function was assessed at variable intervals by eGFR-creatinine, urine dipstick, and urine PCR, ACR, and/or β2-microglobulin; BMD was evaluated in a single individual. By contrast, 4 cases of TAF-associated acute kidney injury have been reported, 22–25 although none had classic Fanconi syndrome. For example, 2 had nephrotic range proteinuria implying severe glomerular disease 22,23 and 3 had uncontrolled diabetes mellitus or no concomitant serum glucose concentrations reported precluding a diagnosis of normoglycemic glycosuria.…”

“…23,25 Kidney biopsy, performed in one of the cases, revealed acute tubular injury with mitochondrial dysmorphia, but this was in addition to diabetic nephropathy, immune complex deposition, foot process effacement, tubular atrophy, and interstitial fibrosis. 22 Finally, one case had concurrent exposure to gentamicin and carboplatin which likely contributed to acute tubular injury, 25 while another had presented 2 months after switching to TAF from TDF, which he had apparently tolerated well for 10 years. 24 Retinol-binding protein is a sensitive marker of (nontreatment limiting) renal tubular dysfunction, and RBPCRdefined renal tubular dysfunction is more common in people with HIV (22.5%-37.7%) as compared with HIV-negative controls (7.6%).…”

“…16,17 Whether TAF can be safely used in individuals who experienced PRT on TDF remains uncertain: Although several case reports have shown resolution or nonrecurrence of Fanconi syndrome on switching from TDF to TAF, [18][19][20][21] others reported kidney injury in individuals soon after switching to TAF. [22][23][24][25] We conducted a clinical trial of TAF (plus emtricitabine) in people with HIV infection and a history of treatment-limiting PRT on TDF. We hypothesized that TAF exposure in this group of individuals would not result in recurrent PRT and have a minimal impact on renal and bone biomarkers.…”

Tenofovir alafenamide nephrotoxicity: a case report and literature review

“…Case reports of TAF-associated nephrotoxicity were reviewed and shown in Table 1 . [ 5 – 9 ]. Most of the cases had either underlying renal abnormalities or concurrent use of nephrotoxic medications.…”

“…It is recommended as the preferred nucleotide analogue reverse transcriptase inhibitor (NRTI) backbone of the ART in the current HIV treatment guidelines [ 3 , 4 ]. Since TAF has become more widely available, sporadic cases of acute kidney injury in patients using TAF is increasing [ 5 – 9 ]. Here we present a patient with TAF-containing ART regimen who came to our hospital with kidney injury.…”