Chronic kidney disease and albuminuria in children with sickle cell disease

Abstract

Background and objectives: Sickle cell nephropathy begins in childhood and may progress to renal failure. Albuminuria is a sensitive marker of glomerular damage that may indicate early chronic kidney disease (CKD).

Design, setting, participants, & measurements: The aims of this study were to determine the cross-sectional prevalence and clinical correlates of albuminuria and CKD among children with sickle cell disease (SCD). Over a 10-year period (1995 to 2005) 410 pediatric SCD patients ages 2 to 21 years were enrolled: 261 with hemoglobin SS (HbSS) or HbSβ(0) thalassemia (HbSβ(0)) and 149 with HbSC or HbSβ(+) thalassemia (HbSβ(+)). The albumin/creatinine ratio (ACR) of spot-urine specimens and serum creatinine were measured; abnormal albuminuria was defined as urinary ACR ≥ 30 mg/g.

Results: The prevalence of abnormal albuminuria was 20.7% (23.0% in HbSS/HbSβ(0), 16.8% in HbSC/HbSβ(+)). Among HbSS/HbSβ(0), abnormal albuminuria was associated with increasing age and lower baseline hemoglobin. GFR, estimated in 189 patients using the updated Schwartz formula, correlated negatively with age (r = -0.27, P = 0.0002). CKD defined according to the Kidney Disease: Improving Global Outcomes study was present in 26.5% (50 of 189) of patients: stage 1 in 27 (14.8%) and stage 2 in 22 (11.6%). In multivariate analysis, age and HbSC/HbSβ(+) genotype were associated with CKD.

Conclusions: This is the first study to stage CKD in children with SCD and highlights a high prevalence of albuminuria and glomerular injury early in life. Detecting CKD in childhood could allow for earlier intervention and prevention of renal failure in adulthood.

Figure 1.

Inverse correlation of estimated GFR with age in (A) HbSS/Sβ⁰ patients (r = −0.19, P = 0.048) and (B) HbSC/HbSβ⁺patients (r = −0.29, P = 0.01).

Figure 2.

Prevalence and stages of chronic kidney disease (CKD) in HbSS/Sβ⁰ and HbSC/Sβ⁺. (A) In HbSS/Sβ⁰, CKD occurred in 11 of 73 (15.1%) children ages 2 to 12 years versus 12 of 40 (30%) children ages 13 to 21 years (P = 0.06). (B) In HbSC/Sβ⁺, CKD occurred in 11 of 41 (26.8%) children ages 2 to 12 years versus 16 of 35 (45.7%) children ages 13 to 21 years (P = 0.09).