Background:  Deterioration of renal function among HIV⁺ patients is recognized to be caused by traditional renal risk factors, HIV itself, and exposure to ART. The contribution of immunodeficiency has not been well characterized. Our aim was to prospectively evaluate the rate of and factors associated with deterioration of renal function by assessing changes in estimated glomerular fitration rate (eGFR).

Methods:  eGFR was calculated using the Cockcroft-Gault and modification of diet in renal disease (MDRD) equations after standardization for body-surface area. Deterioration of renal function was defined as 2 consecutive eGFR ≤60 mL/minute/1.73 m² or a confirmed 25% decline in eGFR. Baseline was defined as the date of the first eGFR. Multivariable Cox models, stratified by center, were adjusted for confounders including time-updated exposure to ART, hypertension, diabetes, smoking, and cardiovascular events.

Results:  We included 5526 patients. At baseline the median age was 43 (IQR 38 to 51), current and nadir CD4 count 453 cells/µL (IQR 310 to 640) and 148 cells/µL (55 to 250), respectively, and 75% had HIV RNA <500 copies/mL. During follow-up, eGFR was measured 31,650 times (5 per patient, IQR 4 to 7; median time between eGFR 4 months (3 to 6), 130 patients (2.4%) with the mean of the first 2 eGFR >60 experienced a confirmed eGFR ≤60 and 175 patients (3.2%) a confirmed 25% decline in eGFR (incidence rates 13.4 (95%CI 11.1 to 15.7) and 17.3 (14.4 to 19.9)/1000 patient-years of follow-up, respectively) (see the figure); 41 patients experienced both outcomes. Using the Cockcroft-Gault equation, a 2-fold higher latest CD4 cell count was associated with 31% lower risk of developing a confirmed deterioration of renal function (adjusted relative hazard [RH] = 0.69; 0.55 to 87, p = 0.0034). CD4 nadir was not associated with deterioration of renal function (RH = 1.03/2-fold higher; 0.89 to 1.19; p = 0.74). A prior AIDS diagnosis was associated with increased risk of deterioration of renal function by 75% (RH = 1.75; 1.10 to 2.79; p = 0.018). Hepatitis C virus (HCV) antibody-positive patients also had an increased risk of deterioration of renal function (RH = 2.67; 1.58 to 4.52; p = 0.0002). Other independent risk factors were diagnosis of a cardiovascular event, HIV RNA levels, baseline eGFR, and time of inclusion into the study. Repeating the analysis for a confirmed 25% decline in GFR, the adjusted RH per doubling of the CD4 cell count was 0.75 (0.64 to 0.88). Similar results were obtained using the MDRD equation.

Conclusions:  Deterioration of renal function occurs in 2 to 3% of the patients over a period of 2 to 3 years of follow-up, and is associated with current levels of immunodeficiency, in addition to traditional risk factors.