Association between hemolysis and albuminuria in adults with sickle cell anemia

Abstract

Studies have questioned whether renal dysfunction in sickle cell disease is linked to hemolysis-associated vasculopathy. We have investigated renal function and markers of hemolysis in a cohort of 424 adult African-British patients with sickle cell disease. While significant associations were found in HbSS and HbSβ(0) (sickle cell anemia) patients with and without controlling for covariates between hemolytic markers and albuminuria, the associations were not significant in patients with HbSC. Estimated glomerular filtration rate, a marker of renal function, correlated significantly with reticulocyte count and bilirubin. Alpha thalassemia, present in 34% of the sickle cell anaemia patients, had a protective effect against albuminuria in this group. Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia.

Figure 1.

(A) ACR as a continuous (upper panels) and dichotomous (lower panels) variable vs. age in HbSS + HbSβ⁰ group (left), and HbSC group (right) panels. Bar charts: error bars=95% confidence interval. The geometric (geom) mean was derived by anti-logging the fitted values of the interval regression of log(ACR) on age group (as categorical variable). When ACR was analyzed as a dichotomous variable, a cut-off value of ≥4.5mg/mmol was applied (referred to as microalbuminuria). (B) Effect of α-thalassemia status in HbSS + HbSβ⁰ on ACR with age as a continuous (left: P<0.0005, 95%CI −1.22,−0.38) and dichotomous variable (right panel; P=0.001, 95%CI −3.01,−0.82). The geometric (geom) mean was derived by anti-logging the fitted values of the interval regression of log(ACR) on age group (as categorical variable), the binary variable for alpha-thal (indicating the presence of one or more deletions) and their interaction. When ACR was analyzed as a dichotomous variable, a cut-off value of ≥4.5mg/mmol was applied (referred to as microalbuminuria). (C) Distribution of MDRD eGFR according to genotype and age in HbSS + HbSβ⁰ and HbSC group. Thick line represent cubic spline fit; thin lines represent 95% confidence interval of fit.