Publications

OBJECTIVE

To describe the incidence of rapid kidney function decline (RKFD), and stage 3 chronic kidney disease (CKD) in HIV-1-infected adults initiated on tenofovir-containing antiretroviral therapy.

METHODS

A retrospective cohort study at the infectious diseases clinic of Tygerberg Academic Hospital in Cape Town, South Africa. Patients with more than 3 ml/min per year decline in estimated glomerular filtration were classified as having RKFD, and stage 3 CKD was defined as a value less than 60 ml/min per 1.73 m. We used logistic and Cox proportional hazards regression models to determine factors associated with RKFD and stage 3 CKD.

RESULTS

Of 650 patients, 361 (55%) experienced RKFD and 15 (2%) developed stage 3 CKD during a median interquartile range follow-up time of 54 (46.6-98) weeks. For every 10-year increase in age and 10 ml/min lower baseline estimated glomerular filtration, the odds of RKFD increased by 70% [adjusted odds ratio = 1.70, 95% confidence interval (CI) 1.36-2.13] and 57% (adjusted odds ratio = 1.57, 95% CI 1.38-1.80), respectively. Each 10-year older age was associated with a 1.90-fold increased risk of developing stage 3 CKD (adjusted hazard ratio = 1.90, 95% CI: 1.10-3.29). Women had about four-fold greater risk of stage 3 CKD compared with men (adjusted hazard ratio = 3.96, 95% CI: 1.06-14.74).

CONCLUSION

About half of our study population developed RKFD but only 2% progressed to stage 3 CKD. Approaches that provide balanced allocation of limited resources toward screening and monitoring for kidney dysfunction and HIV disease management are critically needed in this setting.

Fibroblast growth factor23 (FGF23), an early marker of kidney dysfunction, is associated with cardiovascular death. Its role in HIV-positive individuals is unknown. We measured FGF23 in 100 HIV-negative and 191 HIV-positive nondiabetic adults with normal baseline estimated glomerular filtration rate (GFR). We measured GFR by iohexol annually, albumin-creatinine ratio (ACR) every 6 months, as well as pulse wave velocity, carotid plaque, and carotid intima media thickness (IMT) at baseline and 2 years. Progressive albuminuria was defined as follow-up ACR ≥2-fold than baseline and ≥30 mg/g. Regression models assessed associations of FGF23 with baseline factors and longitudinal changes in disease markers. FGF23 levels were similar in HIV serostatus. Among HIV-positive persons, factors independently associated with higher baseline FGF23 levels included female (adjusted ratio of geometric means [95% CI],1.46 [1.21,1.76]), serum phosphorus (1.20 [1.03,1.40]), HCV (1.31 [1.10,1.56]) and non-suppressed HIV RNA (1.27 [1.01,1.76]). At baseline, FGF23 was not associated with GFR, albuminuria, carotid plaque, or carotid IMT in cross-sectionally adjusted analysis of HIV-positive individuals. However, higher baseline FGF23 was associated with progressive albuminuria (odds ratio1.48 [95% CI]:1.05,2.08) and a more rapid increase in IMT (13 μm/year, 95% CI,3,24). These findings suggest a role for FGF23 in HIV-positive populations in identifying patients at greater risk for cardiovascular and kidney disease.