title: Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study.
abstract: 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, Côte 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 Sβ(0); SC and Sβ(+)) with further stratification by age and country.
  
  
  RESULTS
  The study is ongoing because of follow-up. 2582 patients with sickle cell disease were included (1776 SS, 136 Sβ(0), 511 SC, and 159 Sβ(+)). 644 patients with the SS and Sβ(0) phenotypes (33·7%, 95% CI 31·6-35·8) and 110 with the SC and Sβ(+) phenotypes (16·4%, 13·6-19·2) had albuminuria. In the SS and Sβ(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 Côte 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 Sβ(0) phenotypes. The magnitude of the association of albuminuria with haemoglobin and lactate dehydrogenase concentrations increased with age. In the SC and Sβ(+) 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.
  
  
  CONCLUSIONS
  Hyperhaemolysis is associated with albuminuria, with an age-dependent effect, in the SS and Sβ(0) phenotypes only, suggesting a different pathological mechanism for glomerular disease in the patients with SC and Sβ(+) 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.
  
  
  BACKGROUND
  Paris Cité Sorbonne University (GrEX project) and Cardiology and Development.
authors.affiliation: Internal Medicine, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, Paris, France; UMR S970, Université Paris Descartes, Inserm, Paris, France. Electronic address: brigitte.ranque@egp.aphp.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Ranque
authors.affiliation: Cardiology Unit, Groupement des Hôpitaux de l'Université Catholique de Lille, Lille, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Menet
authors.affiliation: Cardiology Unit, Centre Hospitalo-Universtaire de Fann, Dakar, Senegal.
authors.forename: Ibrahima Bara
authors.initials: IB
authors.lastname: Diop
authors.affiliation: UMR S970, Université Paris Descartes, Inserm, Paris, France.
authors.forename: Marie Michèle
authors.initials: MM
authors.lastname: Thiam
authors.affiliation: Centre de Recherche et Lutte contre la Drépanocytose, Bamako, Mali.
authors.forename: Dapa
authors.initials: D
authors.lastname: Diallo
authors.affiliation: Centre National de Transfusion Sanguine, Dakar, Senegal.
authors.forename: Saliou
authors.initials: S
authors.lastname: Diop
authors.affiliation: Pediatrics Unit, Centre Hospitalier National d'Enfants Albert Royer, Dakar, Senegal.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diagne
authors.affiliation: Hematology Unit, CHU de Yopougon, Abidjan, Côte d'Ivoire.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Sanogo
authors.affiliation: Cardiology Unit, Hôpital Général, Yaoundé, Cameroon.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kingue
authors.affiliation: Cardiology Unit, Centre Mère et Enfant de la Fondation Chantal Biya, Yaoundé, Cameroon.
authors.forename: David
authors.initials: D
authors.lastname: Chelo
authors.affiliation: Pediatrics Unit, Centre Hospitalier d'Essos, Yaoundé, Cameroon.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Wamba
authors.affiliation: Cardiology Unit, Centre Gynéco-obstétrique, Bamako, Mali.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Diarra
authors.affiliation: Institut de Cardiologie, Abidjan, Côte d'Ivoire.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Anzouan
authors.affiliation: Institut de Cardiologie, Abidjan, Côte d'Ivoire.
authors.forename: Roland
authors.initials: R
authors.lastname: N'Guetta
authors.affiliation: Centre de Recherche et Lutte contre la Drépanocytose, Bamako, Mali.
authors.forename: Cheick Oumar
authors.initials: CO
authors.lastname: Diakite
authors.affiliation: Centre de Recherche et Lutte contre la Drépanocytose, Bamako, Mali.
authors.forename: Youssouf
authors.initials: Y
authors.lastname: Traore
authors.affiliation: Cardiology Unit, Centre Hospitalo-Universtaire de Fann, Dakar, Senegal.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Legueun
authors.affiliation: Pediatrics Unit, Centre Hospitalier National d'Enfants Albert Royer, Dakar, Senegal.
authors.forename: Indou
authors.initials: I
authors.lastname: Deme-Ly
authors.affiliation: Centre Pasteur du Cameroun, Yaoundé, Cameroon.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Belinga
authors.affiliation: Hematology Unit, CHU de Yopougon, Abidjan, Côte d'Ivoire.
authors.forename: Kouakou
authors.initials: K
authors.lastname: Boidy
authors.affiliation: Hematology Unit, CHU de Yopougon, Abidjan, Côte d'Ivoire.
authors.forename: Ismael
authors.initials: I
authors.lastname: Kamara
authors.affiliation: UMR S970, Université Paris Descartes, Inserm, Paris, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Tharaux
authors.affiliation: Cardiology Department, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, Paris, France; UMR S970, Université Paris Descartes, Inserm, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jouven