Association between Endothelial Dysfunction, Biomarkers of Renal Function, and Disease Severity in Sickle Cell Disease

Background Endothelial dysfunction (ED), as ascertained by brachial artery flow-mediated dilation (FMD), is a known feature of sickle cell disease (SCD), which is present both in crisis and in steady state. The assessment of FMD was introduced to examine the vasodilator function. Our objective was to establish the relationship between ED determined by FMD, biomarkers of renal dysfunction, and biomarkers of disease severity in SCD subjects asymptomatic of renal disease. Methods We enrolled 44 patients with homozygous SCD in steady state and 33 age-and sex-matched controls between 2013 and 2014 in a tropical tertiary hospital. Ultrasonographic FMD of the right brachial artery, renal arterial Doppler, complete blood count, creatinine, fetal hemoglobin, soluble P-selectin, and cystatin C (Cys-C) levels were determined. Using the median FMD value of the control group, the SCD subjects were further classified into two groups for comparison. Results The median FMD in SCD subjects of 3.44 (IQR, 0.00-7.08) was significantly lower than that of controls, which was 5.35 (IQR, 3.60-6.78; P=0.04). There was negative correlation between FMD and Cys-C levels (r=-0.372; P=0.01) along with renal artery resistivity index (RARI; r=-0.307; P=0.04) in SCD subjects. Additionally, Cys-C level was significantly higher in SCD subjects with FMD < 5.35. Conclusions Brachial artery FMD was significantly lower in SCD subjects compared with a control group. Cys-C and RARI show a negative correlation with FMD, indicating that renal function is related to ED in SCD.