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Diagnosis: Indinavir Nephrotoxicity

Indinavir is an alpha-amino acid amide protease inhibitor used as a treatment therapy for Human immunodeficiency virus (HIV) infections. The FDA approved indinavir in 1996 as it was among the first HIV protease inhibitors authorized in the United States. Indinavir has decreased the likelihood of death due to AIDS progression. It is no longer available in the United States or Europe as it has many adverse effects, and there are better drugs (Pollak EB, Parmar M. Indinavir. 2022 Jul 15. In: StatPearls [Internet]. StatPearls Publishing; 2022. PMID: 32119283. [PubMed link]). So, the case was selected for historical value.

Since the inclusion of indinavir in the armamentarium of anti-retroviral drugs, its association with the frequent occurrence of renal calculi has been well appreciated. The initial product monograph reported an incidence of urinary calculi of approximately 4%. However, subsequent research demonstrated that incidence of nephrolithiasis was much higher, rising to 43.2% in some studies. The basic factor in the pathogenesis of indinavir nephrolithiasis is the reduced solubility of indinavir at urine pH > 5.5. Indinavir crystallises as very large needle-shaped crystals which form large plates or radiating aggregates. Such crystals easily obstruct the renal tubules and form urinary calculi. Indinavir therapy was also associated with the occurrence of reversible acute renal failure related to crystal formation and interstitial nephritis; the renal failure usually reversible after indinavir withdrawal (Lucas C, at al. Indinavir nephropathy: A reversible cause of progressive renal disease. Port J Nephrol Hypert 2007;21(3):235-9 [Full Text Link]).

Recent studies have analyzed the effects of indinavir as an anti-cancer agent. Human papillomavirus is induced by increased expression of eukaryotic translation initiation factor 4E (eIF4E), potentially leading to cervical cancer. Indinavir is an inhibitor of eIF4E. Therefore, recent research has examined its role as a possible cervical cancer treatment. These observations may lead to new therapeutic indications of protease inhibitors to treat cervical carcinoma; however, substantial research is needed before clinical approval (Pollak EB, Parmar M. Indinavir. 2022 Jul 15. In: StatPearls [Internet]. StatPearls Publishing; 2022. PMID: 32119283. [PubMed link]). In addition, this drug could potentially be used in infection by other viruses as HTLV-1.

Among the most important factors that increase the probability of renal crystal deposition are: severe volume depletion, underlying renal failure, excessive dosage of these drugs, and previous metabolic disorders. As we can see, in the case that we present, we found the history of treatment with indinavir added to the severe volume depletion that the patient presented (dehydration due to gastroenteritis), this facilitated the deposit of these crystals within the tubules leading to acute renal failure.

The renal adverse effects of indinavir (intrarenal crystal deposition or urolithiasis) may simply manage by the discontinuation of indinavir administration, urine acidification, as well as the possible early insertion of bilateral double-J ureteral stents (Kalaitzis C, ety al. Urological management of indinavir-associated acute renal failure in HIV-positive patients. Int Urol Nephrol. 2007;39(3):743-6. [PubMed link]).

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