Introduction Tenofovir (TDF) is a commonly used nucleotide reverse transcriptase inhibitor, effective in the management of HIV-positive individuals and chronic Hepatitis B infection. We report two cases that highlight the rare but significant nephrotoxic adverse effects of TDF on mitochondrial-rich proximal renal tubular cells, causing acute and chronic kidney impairment. We also show that removal of TDF results in partial improvement of the renal dysfunction.
Case reports The first case describes a patient with long standing HIV who develops Fanconi syndrome, nephrogenic diabetes insipidus, acute tubular necrosis and tubulointerstitial nephritis, three years after TDF initiation. The second case reports a patient who developed acute severe kidney injury, requiring management with emergency haemodialysis, two weeks after TDF was initiated. In both cases renal biopsy showed extensive tubular injury and histology consistent with TDF induced renal injury. Both individuals had improved renal function following TDF cessation, but ongoing chronic kidney disease.
Discussion Nephrotoxicity has been demonstrated in 17–22% of TDF-treated patients and occurs due to TDF accumulation in cell membrane transporters within proximal tubular cells, where it targets the mitochondria. TDF-related nephrotoxicty presents in a number of ways including proximal tubular dysfunction, acute and chronic kidney injury and a partial or complete Fanconi syndrome. Histological findings most commonly show proximal tubular injury. TDF specific histology is related to prominent eosinophillic intracytoplasmic inclusions, representing giant mitochondria.
Conclusion TDF is a popular choice of antiretroviral therapy due to its efficacy, low side effect profile and use in monotherapy regimes. These cases highlight the potentially life-threatening complications of TDF-related nephrotoxicty. It also shows the importance of renal function monitoring and the withdrawal of TDF to prevent chronic renal impairment.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.