Atazanavir nephrotoxicity

Abstract

Atazanavir is commonly used as one of the key drugs in combination antiretroviral therapy for human immunodeficiency virus (HIV). However, atazanavir has the potential to yield its crystalline precipitation in urine and renal interstitial tissues, leading to crystalluria, urolithiasis, acute kidney injury (AKI) or chronic kidney disease (CKD). In epidemiological studies, atazanavir/ritonavir alone or in combination with tenofovir has been associated with increased risk of progression to CKD. However, renal biopsies were not provided in these studies. Case reports showing an association between atazanavir use and tubulointerstitial nephritis among HIV-infected individuals provide clues as to the potential causes of atazanavir nephrotoxicity. We now review atazanavir-related kidney disease including urolithiasis, renal dysfunction and interstitial nephritis and illustrate the review with a further case of atazanavir-associated kidney injury with sequential renal biopsies. There are two forms of atazanavir-associated tubulointerstitial nephritis: acute tubulointerstitial nephritis that may develop AKI rapidly (in weeks) after initiation of atazanavir, and chronic tubulointerstitial nephritis that may develop progressive CKD slowly (in years) with granuloma and intrarenal precipitation of atazanavir crystals as well as crystalluria. Caution should be exercised when prescribing atazanavir to patients at high risk of CKD, and therapy should be reevaluated if renal function deteriorates, especially associated with crystalluria and hematuria.

Clinical Pharmacology in HIV Therapy

“…Likewise and equally important, some of these agents have been shown to be directly nephrotoxic, inducing a variety of kidney disorders ranging from AKI, acute interstitial nephritis, kidney stones, crystalline nephropathy, and CKD to proximal and distal tubular kidney dysfunction (1,(6)(7)(8)(9)(10)(11). Understanding the pharmacologic characteristics of these agents is essential in this context.…”

Effects of a switch from tenofovir‐ to abacavir‐based antiretroviral therapy, with or without atazanavir, on renal function

“…Among the PIs in current use, atazanavir has been associated with nephrolithiasis [12,13] and chronic kidney disease (CKD) in cohort studies [6,7]. The potential mechanism of the interaction between TDF and atazanavir, as it relates to renal dysfunction, remains unclear [14,15]. …”

HIV and the kidney in the acute medical unit

“…16 Although rare, atazanavir has also been associated with acute TIN, and a more insidious, scarring chronic granulomatous TIN driven by intra-tubular crystal deposition. 17 Atazanavir is best avoided in the setting of AKI.…”