Atazanavir/ritonavir more likely to cause kidney stones than other ritonavir-boosted protease inhibitors

Treatment with ritonavir-boosted atazanavir is associated with a much higher risk of kidney stones compared to other ritonavir-boosted protease inhibitors, Japanese investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. There was also a high recurrence rate of kidney stones in people who continued to take atazanavir/ritonavir.

“The incidence of renal stones in patients on ATV/r [atazananvir/ritonavir] was approximately 10 times higher than those on other PIs [protease inhibitors],” comment the investigators. “Replacement of ATV/r with other drugs should be considered in patients diagnosed with renal stones to prevent further deterioration in renal function.”

Ritonavir-boosted atazanavir (Reyataz) is among the drugs recommended for first-line antiretroviral therapy. Taken once daily, it has a potent anti-HIV effect and a mild side-effect profile.

Nevertheless, there is some evidence that therapy with the drug may increase the risk of kidney stones. Despite this, relatively little is known about the incidence of this side-effect in people treated with atazanavir/ritonavir compared to other ritonavir-boosted protease inhibitors.

Investigators in Tokyo therefore designed a retrospective study involving 1240 people who were treated with antiretroviral therapy based on a ritonavir-boosted protease inhibitor between 2004 and 2010.

Just over a third (38%) of the people in the study received atazanavir/ritonavir.

Kidney stones were diagnosed in a total of 35 people, 31 of whom were taking atazanavir/ritonavir.

This meant that 7% of people in the study who were treated with atazanavir/ritonavir developed kidney stones, compared to 0.5% in people taking other ritonavir-boosted protease inhibitors.

The incidence of kidney stones was 24 per 1000 person years in the atazanavir/ritonavir group. This compared to just 2 per 1000 person years in the people taking another boosted protease inhibitor.

The authors’ first statistical analysis showed that atazanavir/ritonavir was associated with a tenfold increase in the risk of kidney stones (HR = 10.44; 95% CI, 3.68-29.59; p < 0.001).

This association was largely unchanged after taking into account factors such as age, gender, weight and other risk factors for kidney stones (HR = 10.08; 95% CI, 3.48-29.17; 0 < 0.001).

Treatment with atazanavir has been associated with a non-dangerous increase in bilirubin. However, there was no association between this and the risk of kidney stones.

A total of 18 people continued to take atazanavir/ritonavir after the diagnosis of kidney stones. There was a recurrence of renal stones in six of them. This occurred a median of five months after the first diagnosis.

Kidney function (measured by eGFR) declined more significantly in people with kidney stones than in people who did not develop this complication (p < 0.001).

Indeed, the investigators note “the development of renal stone is a risk factor for CKD [chronic kidney disease].” They caution “the high incidence of renal stone with ATV/r use may in part contribute to ATV/r being a risk for CKD. Thus, ATV/r should be carefully introduced in patients with concomitant predisposing risk factors for CKD.” The authors speculate that the high incidence of kidney stones in the atazanavir/ritonavir-treated people could be because the drug is partly excreted in urine.

 They conclude, “ATV/r use was an independent risk factor for renal stones in a robust statistical model.” 

Hamada Y et al. High incidence of renal stones in HIV-infected patients on ritonavir-boosted atazanavir than in those on other on other protease inhibitor-containing antiretroviral therapy. J Acquir Immune Defic Syndr, online edition, 2012.