High Incidence of Renal Stones Among HIV-Infected Patients on Ritonavir-Boosted Atazanavir Than in Those Receiving Other Protease Inhibitor-Containing Antiretroviral Therapy

Abstract

The incidence of renal stones was substantially higher among patients in the ATV/r group, compared with patients in the other PIs group. Continuation of ATV/r after diagnosis of renal stones was associated with a high rate of recurrence. Switching ATV/r to other ARVs is warranted in patients who develop renal stones.

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].…”

Recurrent nephrolithiasis associated with atazanavir use

“…Some of these patients were diagnosed solely by clinical findings or urine/stone analysis, whereas others had stones visualised on CT or ultrasonography 7. Hamada et al 4 compared the incidence of nephrolithiasis in patients receiving atazanavir with those receiving other protease inhibitors and found that atazanavir was associated with a substantially higher rate of stone formation and that discontinuation of atazanavir resulted in no further stone formation. It has been suggested that patients with low water intake, higher urinary pH, a history of nephrolithiasis or impaired metabolism of atazanavir (eg, in hepatic dysfunction) have a higher rate of stone formation while on this medication 2 5.…”

“…Similar to indinavir, of which 19% is excreted unchanged in urine, approximately 7% of atazanavir is excreted unchanged in urine 3. The aetiology of nephrolithiasis associated with atazanavir is not well understood but reports have demonstrated that atazanavir is associated with a higher rate of nephrolithiasis than other antiretroviral agents 4 5. In addition, several studies have shown that the compound itself contributes to stone composition 6 – 9.…”

Disappearance of Renal Stones in an HIV-1-Infected Patient After Reduction of Atazanavir Dose

“…Atazanavir/ritonavir administration has been recently showed to be a risk factor for symptomatic nephrolithiasis 1 .Atazanavir could promote kidney stones trough similar mechanisms to indinavir--induced urolithiasis (drug crystallization and precipitantion in the kidneys) 1 .de Lastours and colleagues showed high levels of atazanavir and darunavir in urine with crystalluria in asymptomatic HIV--infected patients, being urinary atazanavir and darunavir concentrations significantly higher than plasma levels 2 . We report the first case of an HIV--1--infected patient on atazanavir/ritonavir (300/100 mg daily) with recurrent kidney stone episodes, who benefit from a atazanavir dose reduction.…”

“…We report the first case of an HIV--1--infected patient on atazanavir/ritonavir (300/100 mg daily) with recurrent kidney stone episodes, who benefit from a atazanavir dose reduction. Hamada et al recently reported in a single center cohort study that the incidence of renal stones is approximately 10 times higher among patients on ATV/r--containing antiretroviral therapy (ART) than those on other PIs--containing ART 1 .The mechanism of atazanavir/ritonavir--induced renal stone formation could be the crystallization of atazanavir, as in the case of indinavir--induced renal stones 6 .Although in our case ATV concentrations were higher in urine than in plasma, as expected 2 , a dramatic decrease of urine concentration (by 88%) was showed after dose reduction to boosted 150 mg daily, with disappearance of symptoms and signs of renal stones. This finding confirms the need of a threshold of ATV urinary concentration to form precipitation in crystals 2 .ATV plasma concentrations are known to correlate with serum bilirubin level and switch to unboosted ATV has been described to reduce the risk of hyperbilirubinemia 8 .Rockwood et al 7 found a close association between hyperbilirubinemia and the development of renal stones, supporting the association of both with plasma exposure, and, for the latter, with urinary exposure too.…”