Development of chronic kidney disease and antiretroviral use in EuroSIDA cohortsince 2004

An analysis on the risk factors associated with progression to chronic kidney disease (CKD) observed in the European observational EuroSIDA cohort was reported by Mocroft and colleagues in the 17 July edition of the journal AIDS.

This analysis included data from almost 7000 (out of almost 12,000) HIV-positive patients followed from 2004 when serum creatinine measurements were routinely collected. Inclusion criteria included at least three serum creatinine measurements (median 9; IQR 612) plus height and weight to calculate estimated glomerular filtration rate (eGFR). CKD was defined as either confirmed eGFR of 60 mL/min per 1.73 m2 or below (if baseline eGFR was >60) or confirmed 25% decline in eGFR (if baseline was <60). Cumulative drug and class exposure was included in the risk model together with all standard HIV and renal factors.

At baseline, eGFR was <60 in 4% (n=278) and >90 in 60% of the study participants. Median follow-up was 3.7 years (IQR 2.85.7). During 21,482 person-years follow-up, 225 people progressed to CKD, mostly (n=203) changing from >60 to <60 (n=150 >70). This gave an annual incidence of 1.05 per 100 PYFU (95%CI: 0.911.18). Only 27 patients with baseline >90 progressed to <60.

In multivariate analysis (adjusting for traditional CKD risk factors (age, hypertension, cardiovascular disease, HCV, diabetes, use of nephrotoxic drugs and other confounding variables), increasing cumulative exposure to tenofovir [IRR 1.16, 95% CI 1.061.25, p<0.0001), indinavir (IRR 1.12, 95% CI 1.061.18, p<0.0001), atazanavir (IRR 1.21, 95% CI 1.091.34, p=0.0003) were associated with a significantly increased rate of CKD. A lesser association was reported with lopinavir/r (IRR 1.08, 95% CI 1.011.16, p=0.030), however this was not confirmed in a second analysis and it was reported as a more tenuous association. No other antiretroviral dugs were associated with increased incidence of CKD.

There was a trend for continued exposure to increase risk with atazanavir and indinavir and an initial risk with tenofovir that was stable after 2 years. Excess risks reverted after discontinuing atazanavir and lopinavir/r but remained after discontinuing tenofovir for 12 months before normalising to that of someone without tenofovir exposure. These data were based on relatively small numbers and over short-term follow up.

A significant minority of people also reported renal improvement. 157/225 patients diagnosed with CKD who had >2 subsequent eGFR measurements, 56 later reverted back to an eGFR >60.

The study noted that the generally low prevalence and incidence of CKD within EuroSIDA was consistent other reports and that traditional risk factors (older age, hypertension and diabetes) were also independently associated with CKD in EuroSIDA. Patients with pre-existing excess risk of CKD were more likely to develop progression in they were using tenofovir. No additional risk was found when tenofovir was used with boosted-PIs.