Renin-angiotensin system blockade promotes a cardio-renal protection in albuminuric homozygous sickle cell patients.

Morad Djebbar, Francois Lionnet, Pierre Levy, Robert Girot, Michel Chaignon, Alexei Girshovich, Nathalie Tabibzadeh, Gilles Grateau, Emmanuel Letavernier, Jean-Philippe Haymann, Jean-Benoit Arlet, Yahia Benzerara, Pablo Bartolucci, Virginie Avellino, Anoosha Habibi, Frederic Galacteros, Katia Stankovic Stojanovic, Nadjib Hammoudi

Journal: British journal of haematology 2017;179(5):820-828

PMID: 29048108

Abstract

The management of sickle cell nephropathy (SCN) at an early stage is an important issue to prevent renal and cardiovascular morbidity and mortality. This study aimed to evaluate in this population, whether angiotensin converting enzyme inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10 mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured glomerular filtration rate (mGFR) together with haematological and cardiovascular parameters. A 1-month washout was also performed in order to differentiate short- and long-term ACEIs effects. A decrease in ACR baseline value (>30%) was detected in 62% of cases (mean ACR: 46·4 ± 7·6 and 26·4 ± 3·9 mg/mmol at baseline and 6 months respectively; P = 0·002), whereas mGFR values were unchanged. ACR decrease was detected at 1 month following ACEI initiation (32·9 ± 6·9, P = 0·02) with a persistent trend after withdrawal (P = 0·08). ACEIs also decreased diastolic blood pressure (P = 0·007), pulse wave velocity (P = 0·01), tricuspid regurgitation velocity (TRV; P = 0·04), asymmetric dimethyl arginine (ADMA: P = 0·001) and haemoglobin (P = 0·01) while conventional haemolytic biomarkers were unchanged. Our data suggest that ACEIs are safe and effective at decreasing albuminuria in sickle cell patients with a beneficial effect on specific mortality risk factors, such as TRV and asymmetric dimethyl arginine.

© 2017 John Wiley & Sons Ltd.

Address: Service d'Explorations Fonctionnelles Hôpital Tenon, Assistance Publique-Hopitaux de Paris, Paris, France.; Sorbonne Universites UPMC Univ Paris 06, Paris, France.; Institut National de la Sante et de la Recherche Medicale, UMR-S 1155, Paris, France.; Service de Cardiologie, Hôpital de la Pitie Salpetrière, Assistance Publique-Hopitaux de Paris, Paris, France.; Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.; Centre for Sickle Cell Disease, Hôpital Tenon, Assistance Publique-Hopitaux de Paris, Paris, France.; Centre for Sickle Cell Disease, Hôpital Mondor, Assistance Publique-Hopitaux de Paris, Paris, France.; Centre for Sickle Cell Disease, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France.; Public Health Department, Hôpital Tenon, Assistance Publique-Hopitaux de Paris, Paris, France.
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