Three Kidney Metrics Worse With HIV Than Without in Aging Adults

Having HIV infection raised the chances of impaired kidney function by three standard measures in a Dutch comparison of aging adults living with versus without HIV. In a longitudinal analysis, being HIV positive and taking an unmodified antiretroviral regimen independently predicted greater estimated glomerular filtration rate (eGFR) decline and worsening albuminuria.

HIV infection boosts the risk of chronic kidney disease, most likely through a combination of factors: HIV viremia, nephrotoxic antiretrovirals and traditional risk factors (such as hypertension, diabetes and smoking). To compare kidney function in older adults with or without HIV, AGEhIV cohort investigators tracked the prevalence of several variables: renal impairment, albuminuria, proximal renal tubular dysfunction (PRTD) and changes in eGFR and albuminuria over time.

AGEhIV consists of 598 HIV-positive people recruited from an Amsterdam HIV outpatient clinic at age 45 or older and 550 HIV-negative people with similar sociodemographic and behavioral traits recruited from an Amsterdam sexual health clinic and the Amsterdam Cohort Studies on HIV/AIDS. The researchers measured kidney-specific markers in randomly collected samples. They used multivariable linear regression to determine whether HIV is associated at baseline with renal impairment (eGFR <60 mL/min), albuminuria (albumin/creatinine ratio ≥3 mg/mmol) or PRTD (retinol-binding protein/creatinine ratio >2.93 μg/mmol and/or fractional phosphate excretion >20% with plasma phosphate <0.8 mmol/L). In a longitudinally tracked set of participants, the researchers also used multivariable linear regression to compare rapid declines in eGFR and worsening albuminuria in HIV-positive people continuing an unmodified antiretroviral regimen versus the HIV-negative comparison group.

The analysis involved 596 HIV-positive and 544 HIV-negative AGEhIV cohort members who had baseline eGFR data. Median overall age stood at 52.5 years and more than 80% of participants were men. The HIV group included a significantly higher proportion of people from Africa (14.3% versus 6.4%, P < .001). Most HIV-positive people (95%) were taking antiretroviral therapy, 94% had a viral load below 200 copies/mL, 73% were taking tenofovir disoproxil fumarate (TDF) and 42% were taking a protease inhibitor.

Significantly higher proportions of the HIV group had renal impairment (4.7% versus 2.0%, P = .01), albuminuria (24.4% versus 5.6%, P < .001) and PRTD (40.1% versus 8.6%, P < .001). Logistic regression analysis adjusted for age, sex, African descent, cigarette smoking and other variables determined that cohort members with HIV had significantly higher odds of renal impairment (adjusted odds ratio [aOR] 2.1, 95% confidence interval [CI] 1.0 to 4.4, P = .05), albuminuria (aOR 5.8, 95% CI 3.7 to 9.0, P < .001) and PRTD (aOR 7.1, 95% CI 4.9 to 10.2, P < .001).

Older age was significantly associated with higher odds of renal impairment, albuminuria and PRTD. Other independent predictors of renal measures were current smoking (albuminuria), former smoking (PRTD), use of antihypertensives (albuminuria), higher systolic blood pressure (albuminuria), diabetes (albuminuria), cardiovascular disease (PRTD), cumulative TDF exposure (PRTD) and higher nadir body weight (lower odds of albuminuria).

The longitudinal analysis included 377 people with HIV and 479 without HIV with approximately four years of follow-up. A significantly higher proportion of people with HIV had rapid eGFR decline (5.8% versus 2.3%, P = .008) or worsening albuminuria (11.6% versus 5.0%, P < .001). In an analysis adjusted for age, sex, African descent and other factors, remaining on a baseline antiretroviral regimen was linked to greater eGFR decline (–0.56, 95% CI –0.87 to –0.24 mL/min per year). Linear regression analysis, adjusted for the same variables, determined that HIV infection more than doubled the odds of rapid eGFR decline (aOR 2.2, 95% CI 1.0 to 4.7, P = .04) and significantly increased the odds of worsening albuminuria (aOR 2.4, 95% CI 1.4 to 4.0, P = .001).

Further analysis linked current atazanavir (Reyataz) use to greater odds of rapid eGFR decline (OR 2.61, 95% CI 1.00 to 6.60, P = .04), current smoking predicted higher odds of worsening albuminuria (OR 2.79, 95% CI 1.20 to 6.50, P = .02) and higher baseline eGFR predicted lower odds of worsening albuminuria (OR 0.70, 95% CI 0.60 to 0.80, P < .001).

The investigators concluded that these aging adults with HIV were more likely than a similar HIV-negative group to have renal impairment, albuminuria and PRTD. They proposed that waning renal function with HIV in their longitudinal analysis might reflect exposure to certain antiretrovirals, and they reminded clinicians that "the nephrotoxic potential of antiretroviral regimens should be considered in the management of HIV infection."