Hydroxyurea Is Associated with Lower Prevalence of Albuminuria in Adults with Sickle Cell Disease

Abstract

AbstractAbstract ▪3211▪This icon denotes a clinically relevant abstract Background:Albuminuria is an early manifestation of sickle cell disease (SCD) nephropathy, denoting glomerular injury. Minimal clinical data exist on the association of hydroxyurea (HU) use with albuminuria in adults with SCD. Methods:A cross-sectional study was performed to evaluate the association of HU with the prevalence of albuminuria among adults with SCD using clinical data collected from 2000 to 2011. HU exposure was defined as ≥3 months of therapy prior to assessment of albuminuria. Albuminuria was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g and/or ≥1+ proteinuria on two dipstick measurements at least 2 months apart. A multivariate logistic regression model was constructed from univariate analyses and with covariates previously identified to be associated with albuminuria in SCD, including history of acute chest syndrome, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) use, age, and elevated tricuspid regurgitation jet velocity (TRV). Backward elimination of covariates was used to produce the most parsimonious model. Results:149 adult patients (mean age 38±13 years; 113 with HbSS, 10 HbSß0, 7 HbSß1, 18 HbSC, and 1 HbSD) were included. The prevalence of albuminuria was lower among patients on HU therapy than those not on HU [26/75 (34.7%) vs. 41/74 (55.4%); p=0.01]. Among 112 patients with a measured UACR, median albumin excretion was lower in patients on HU [17.9 (6.0–53.0) vs. 40.5 (7.0–204.9) mg/g; p=0.04]. In univariate analyses, ACEi/ARBuse, hemoglobin level and percent reticulocytes were also related to albuminuria. By multivariate logistic regression model, HU use was associated with a lower risk of albuminuria (odds ratio 0.31, 95% CI 0.12 to 0.81; p=0.02), adjusting for age, ACEi/ARB use, TRV ≥2.5 m/s, systemic hypertension and history of acute chest syndrome. Conclusion:The use of HU was associated with lower prevalence of albuminuria, after controlling for age, ACEi/ARB use, TRV ≥2.5 m/s, systemic hypertension and history of acute chest syndrome. Based upon these findings, the potential of HU to prevent overt nephropathy or the progression of SCD nephropathy to end-stage renal disease merits further investigation.Comparison of clinical and laboratory parameters of patients on and not on hydroxyurea therapyParametersHydroxyurea (N=75)No hydroxyurea (N=74)p*N (%)N (%)Albuminuria26 (34.7)41 (55.4)0.01Microalbuminuria15 (27.3)24 (42.1)0.1Macroalbuminuria6 (10.9)12 (21.1)0.1Sex F:M46:2949:250.5ACEi/ARB use11 (14.7)13 (17.6)0.6NSAID use30 (40.0)26 (35.1)0.5Hypertension17 (22.7)23 (31.1)0.2Diabetes5 (6.7)3 (4.1)0.7Acute chest syndrome71 (94.7)52 (70.3)<0.001Tricuspid regurgitation jet velocity ≥2.5m/s¤17 (37.0)28 (57.1)0.05UACR (mg/g)17.9 (6.0–53.0)40.5 (7.0–204.9)0.04Creatinine (mg/dL)0.7 (0.6–0.9)0.8 (0.6–1.1)0.1eGFR (mL/min)151±55128±580.02Hemoglobin (g/dL)9.1±1.99.0±1.60.8Lactate dehydrogenase (U/L)809 (664–1119)916 (671–1385)0.1Total bilirubin level (mg/dL)1.8 (1.0–2.4)2.2 (1.0–3.3)0.1Parametric continuous variables expressed as mean ± standard deviation; nonparametric continuous variables expressed as median (interquartile range). For continuous variables, data were missing in <10% of subjects.*X2 test or Fisher’s exact test (categorical); t-test or Mann-Whitney U test (continuous). For microalbuminuria, macroalbuminuria and UACR, N=112 (55 on HU, 57 not on HU) ¤For TR jet velocity, N=95 (46 on HU, 49 not on HU). Disclosures:No relevant conflicts of interest to declare.