Brigitte Ranque1, Aymeric Menet2, Ibrahima Bara Diop3, Marie Michèle Thiam4, Dapa Diallo5, Saliou Diop6, Ibrahima Diagne7, Ibrahima Sanogo8, Samuel Kingue9, David Chelo10, Guillaume Wamba11, Mamadou Diarra12, Jean Baptiste Anzouan13, Roland N'Guetta13, Cheick Oumar Diakite5, Youssouf Traore5, Gaëlle Legueun3, Indou Deme-Ly7, Suzanne Belinga14, Kouakou Boidy8, Ismael Kamara8, Pierre-Louis Tharaux4, Xavier Jouven15. 1. 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. 2. Cardiology Unit, Groupement des Hôpitaux de l'Université Catholique de Lille, Lille, France. 3. Cardiology Unit, Centre Hospitalo-Universtaire de Fann, Dakar, Senegal. 4. UMR S970, Université Paris Descartes, Inserm, Paris, France. 5. Centre de Recherche et Lutte contre la Drépanocytose, Bamako, Mali. 6. Centre National de Transfusion Sanguine, Dakar, Senegal. 7. Pediatrics Unit, Centre Hospitalier National d'Enfants Albert Royer, Dakar, Senegal. 8. Hematology Unit, CHU de Yopougon, Abidjan, Côte d'Ivoire. 9. Cardiology Unit, Hôpital Général, Yaoundé, Cameroon. 10. Cardiology Unit, Centre Mère et Enfant de la Fondation Chantal Biya, Yaoundé, Cameroon. 11. Pediatrics Unit, Centre Hospitalier d'Essos, Yaoundé, Cameroon. 12. Cardiology Unit, Centre Gynéco-obstétrique, Bamako, Mali. 13. Institut de Cardiologie, Abidjan, Côte d'Ivoire. 14. Centre Pasteur du Cameroun, Yaoundé, Cameroon. 15. Cardiology Department, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, Paris, France; UMR S970, Université Paris Descartes, Inserm, Paris, France.
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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Paris Cité Sorbonne University (GrEX project) and Cardiology and Development.
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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Paris Cité Sorbonne University (GrEX project) and Cardiology and Development.
Authors: Kabir O Olaniran; Andrew S Allegretti; Sophia H Zhao; Maureen M Achebe; Nwamaka D Eneanya; Ravi I Thadhani; Sagar U Nigwekar; Sahir Kalim Journal: J Am Soc Nephrol Date: 2019-12-06 Impact factor: 10.121
Authors: Amy Geard; Gift D Pule; Bernard Chetcha Chemegni; Valentina J Ngo Bitoungui; Andre P Kengne; Emile R Chimusa; Ambroise Wonkam Journal: Br J Haematol Date: 2017-05-03 Impact factor: 6.998
Authors: Santosh L Saraf; Xu Zhang; Binal Shah; Tamir Kanias; Krishnamurthy P Gudehithlu; Rick Kittles; Roberto F Machado; Jose A L Arruda; Mark T Gladwin; Ashok K Singh; Victor R Gordeuk Journal: Haematologica Date: 2015-07-23 Impact factor: 9.941
Authors: Oyindamola C Adebayo; Lambertus P Van den Heuvel; Wasiu A Olowu; Elena N Levtchenko; Veerle Labarque Journal: Pediatr Nephrol Date: 2021-05-29 Impact factor: 3.651