Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study

Background Chronic kidney disease is one of the leading causes of mortality in patients with sickle cell disease. However, it has been almost exclusively studied in patients with the SS phenotype and in high-income countries, despite more than 80% of patients living in Africa. We looked for the determinants of glomerulopathy in a multinational cohort of patients with sickle cell disease of different phenotypes in sub-Saharan Africa. Methods In the CADRE cohort, we prospectively included patients 3 years and older with sickle cell disease of all haemoglobin phenotypes in Cameroon, Cote d'Ivoire, Mali, and Senegal. All individuals were assessed at steady state. The main outcome of interest was albuminuria defined as a urine albumin-to-creatinine ratio of greater than 30 mg/g. We investigated the clinical and biological determinants (including haemolysis markers) of albuminuria in two main phenotype groups (SS and S beta(0); SC and S beta(+)) with further stratification by age and country. Findings The study is ongoing because of follow-up. 2582 patients with sickle cell disease were included (1776 SS, 136 S beta(0), 511 SC, and 159 S beta(+)). 644 patients with the SS and S beta(0) phenotypes (33.7%, 95% CI 31.6-35.8) and 110 with the SC and S beta(+) phenotypes (16.4%, 13.6-19.2) had albuminuria. In the SS and S beta(0) group, albuminuria was detected in 144 (27%) of 527 children younger than 10 years and its frequency increased with age (29 [48%] of 60 patients aged >40 years). Multivariable analysis showed that albuminuria was associated with age (odds ratio 1.43, 95% CI 1.20-1.71; p<0.0001), female sex (1.35, 1.02-1.82; p=0.045), low haemoglobin (0.79, 0.66-0.93; p=0.006), high lactate dehydrogenase concentrations (1.33, 1.14-1.58; p=0.0009), and, using Cote d'Ivoire as the reference, Mali (2.49, 1.64-3.79; p=0.042) and Cameroon (1.59, 1.01-2.51; p=0.0007) in patients with the SS and S beta(0) phenotypes. The magnitude of the association of albuminuria with haemoglobin and lactate dehydrogenase concentrations increased with age. In the SC and S beta(+) patients, only low haemoglobin (0.69, 0.48-0.97; p=0.029), high blood pressure (1.63, 1.17-2.27; p=0.0017), and Mali (3.75, 1.75-8.04; p<0.0001) were associated with albuminuria. Interpretation Hyperhaemolysis is associated with albuminuria, with an age-dependent effect, in the SS and S beta(+) phenotypes only, suggesting a different pathological mechanism for glomerular disease in the patients with SC and S beta(+) phenotypes. However, both phenotypes are associated with a high prevalence of albuminuria in childhood. Therefore, screening for albuminuria is advised in African children with sickle cell disease to detect early renal damage.