Clinical and Laboratory Correlates of Albuminuria in Sickle Cell Disease

Introduction: Albuminuria is a common and sensitive marker of glomerular injury in SCD, and typically precedes the development of renal insufficiency. We have previously observed that clinical measures of renal function (including serum creatinine and blood urea nitrogen) are significantly associated with SCD-associated pulmonary hypertension (PHT), a complication associated with increased hemolysis. However, the pathogenesis of albuminuria in SCD patients remains uncertain. The purpose of this exploratory study was to evaluate the association of albuminuria with laboratory measures of hemolysis and hemolysis-related complications in SCD.

Methods: Consecutive adult patients followed at the Sickle Cell Clinic at UNC-Chapel Hill were selected onto this ongoing study. Spot urine for microalbumin/creatinine ratio (to assess albumin excretion rate [AER]), serum measures of renal function, markers of hemolysis and other laboratory studies were obtained at the time of evaluation. Doppler echocardiography was used to determine the pulmonary artery systolic pressure, and PHT was subsequently defined using an age-, sex- and BMI-adjusted reference range. We evaluated for associations between microalbumin/creatinine ratio and 25 clinical and laboratory covariates using Spearman’s correlation coefficient for continuous covariates, and the rank sum test for categorical covariates. Reported p-values are for individual tests, unadjusted for multiple comparisons.

Results: Spot urine samples were available in 73 of the 74 evaluated subjects (SS = 62, SC = 8, Sb⁰ = 3, Sb⁺ = 1), mean age, 39.4 years (range 18–71 years). Normoalbuminuria (AER < 30 mg/g creatinine) was observed in 34 subjects, microalbuminuria (AER = 30–299 mg/g creatinine) in 24 subjects and macroalbuminuria (AER ³ 300 mg/g creatinine) in 15 subjects. Microalbumin/creatinine ratio was significantly associated with PHT (p = 0.03) and a history of leg ulcers (p = 0.03), with borderline association with a history of priapism (p = 0.07). We observed significant correlations between microalbumin/creatinine ratio and age (r = 0.32, p = 0.006), systolic blood pressure (r = 0.27, p = 0.02), lactate dehydrogenase (r = 0.24, p = 0.05), and hemoglobin (r = −0.25, p = 0.03). Microalbumin/creatinine ratio was also correlated with cystatin C levels (r = 0.25, p = 0.03), with inverse correlations with glomerular filtration rate (MDRD: r = −0.24, p = 0.04; Cockroft-Gault: r = −0.29, p = 0.03).

Conclusion: In this exploratory study, we found that albuminuria is common in patients with SCD, and is associated with PHT, leg ulcers, systolic blood pressure and laboratory measures of hemolysis. This finding suggests that hemolysis may contribute to the pathogenesis of albuminuria in SCD. The correlation between microalbumin/creatinine ratio and other measures of renal function suggests that microalbuminuria may predict for SCD-associated glomerulopathy. Longitudinal studies evaluating the relationship between microalbuminuria and progressive renal failure in SCD patients are warranted.