Sickle Cell Anemia (SCA) modifies kidney structure and function. Progressive reduction in kidney function begins at very young stages of life with abnormally increased glomerular filtration rate, followed by albuminuria in late childhood. Albuminuria has been associated with poor prognosis. However, albuminuria is often intermittent in individuals with SCA, and its progression over time needs to be better understood. We aimed to investigate the progression of albuminuria and its risk factors in a large prospective cohort of children with SCA.

We recruited steady-state pediatric patients with SCA at ‘Fundação Hemominas'outpatient clinic, Minas Gerais, Brazil. Random-spot urine specimens were collected during routine visits. Albuminuria was defined by urinary albumin/creatinine ratio ≥30 mg/g of creatinine. Participants were prospectively categorized by the presence or absence of albuminuria at baseline and on the follow-up urine test. Participants with albuminuria at baseline and on the follow-up urine test were considered to have persistent albuminuria. Those with no albuminuria at baseline or on the follow-up urine tests were considered to have no albuminuria. Participants with no albuminuria at baseline who developed albuminuria on the follow-up test were considered progressors. Those with albuminuria at baseline but none on follow-up were considered remitters. Baseline steady-state laboratory data were obtained from medical records. Baseline kidney injury biomarkers in urine were measured using multilplex xMAP® assays. Univariate and multivariate analyses were performed using Cox regression.

From 572 children included in the cohort [287 (50.2%) males], 112 (19.6%; 95% CI:16.3%–22.8%) had albuminuria at enrollment; mean age was 12.9±4.6 years. A total of 246 participants (43%) had two samples and were included in the longitudinal analysis. The median follow-up was 2.1 (6m–4y) years, providing 467.9 patient-years. One hundred eight-seven (76%) participants were receiving intensification therapy (HU, chronic blood transfusion, or both). Out of 246 participants, 169 (68.7%) presented no albuminuria, 13 (5.3%) were progressors, 19 (7.7%) remitters, and 45 (18.3%; 95% CI 13.5%–23.1%) had persistent albuminuria. The incidence of persistent albuminuria was 9.6/100 patient-years (95% CI 6.9–12.3). In cox multivariate analysis, persistent albuminuria was associated with older age (HR = 1.1, 95% CI 1.02–1.19; p = 0.018), lower total Hb (HR = 0.75, 95% CI 0.57–0.98; p = 0.040), and higher indirect bilirubin (HR = 1.3, 95% CI 1.11–1.58; p = 0.002) and kidney injury molecule-1 levels (HR = 1.007, 95% CI 1.001–1.013; p = 0.020).

This study provides important findings on the natural history of albuminuria during childhood of individuals with SCA. The prevalence of persistent albuminuria was similar to previously published studies in children with SCA (13% to 30%). Our findings replicated the association of persistent albuminuria with aging, anemia, and higher levels of hemolysis and renal tubular injury markers. These features may allow early identification of individuals at highest risk for persistent albuminuria, enabling therapeutic interventions to prevent the decline of renal function.

This study showed a high frequency of persistent albuminuria in children with SCA. Age, anemia, and biomarkers of hemolysis and renal tubular injury were significantly associated with persistent albuminuria.