Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease

Abstract

Background: Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients.

Methods: We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed for albuminuria either by direct measurement or by urinary chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs) were available for 112 patients. Hydroxyurea exposure was defined as ≥3 months of therapy before the assessment of albuminuria. Albuminuria was defined as either UACR ≥30 mg/g or ≥1+ proteinuria on two separate dipsticks. We constructed a multivariate logistic regression model to assess the association between hydroxyurea and albuminuria.

Results: The prevalence of albuminuria was lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis, hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio 0.28, 95% CI: 0.11-0.75, P = 0.01), adjusting for age, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet velocity, hypertension and acute chest syndrome.

Conclusions: In our population of sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt nephropathy or the progression of sickle cell disease nephropathy to end-stage renal disease, and its use for this indication merits further investigation.

Keywords: albuminuria; chronic kidney disease; hydroxyurea; nephropathy; sickle cell.