Background:  Renal disease is a strong and independent predictor of cardiovascular disease (CVD) in the general population. Systemic endothelial dysfunction may be the link between CVD and proteinuria, albuminuria, and reduced renal function. In a small pilot study, however, we found that these markers of renal disease were not associated with endothelial dysfunction in non-diabetic and non-hypertensive HIV-infected patients. We sought to confirm and extend these findings in a larger study.

Methods:  We performed a cross-sectional analysis of 104 (73% male; 37% non-Hispanic black) non-diabetic, non-hypertensive, HIV-infected patients without known CVD and who either did not require ART or were on a stable ART. The associations between flow-mediated dilation of the brachial artery, a measure of systemic endothelial function, and spot urine protein to creatinine ratio (P/Cr), albumin to creatinine ratio (A/Cr), and renal function (estimated as both creatinine clearance [CrCl] by the Cockcroft-Gault formula and as glomerular filtration rate [GFR] by the simplified MDRD formula) were determined using Spearman Correlation Coefficients and multivariable linear regression models.

Results:  The median (IQR) age and CD4 cell counts were 40 (34, 46) years and 416 (271, 645)/mm³, respectively; 47% were receiving ART and 46% of the entire cohort had HIV-1 RNA levels <400 copies/mL. The median (IQR) flow-mediated dilation (%), nitroglycerin-mediated dilation (%), P/Cr (g/g), A/Cr (g/g), CrCl (mL/min), and GFR (mL/min/1.73 m²) were 5.4 (2.9, 7.3), 15.9 (12.6, 23.2), 0.073 (0.053, 0.10), 0.0037 (0.0023, 0.008), 118 (96, 139), and 102 (90, 119), respectively. In univariate analyses, flow-mediated dilation was significantly and negatively correlated with P/Cr (r = –0.26, p = 0.01) and A/Cr (r = –0.20, p = 0.05), but not with CrCl or GFR. In multivariable analysis, however, P/Cr and A/Cr were no longer associated with flow-mediated dilation after controlling for baseline diameter, age, sex, and race. Similar results were found in the subgroups not receiving ART or in those with HIV-1 RNA ≥400 copies/mL.

Conclusions:  This larger study confirms that systemic endothelial dysfunction may not independently contribute to nephropathy in stable HIV-infected patients without diabetes, hypertension, or known CVD. Renal disease may not be an independent predictor of future cardiovascular events in these patients.