NDT Advance Access originally published online on September 6, 2005
Nephrology Dialysis Transplantation 2005 20(11):2408-2413; doi:10.1093/ndt/gfi111
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Urinary endothelin-1 as a marker of renal damage in sickle cell disease
1 INSERM U702, 2 Department of Day Hospitalization, 3 Department of Vascular Medicine, 4 Hematology Laboratory; Tenon Hospital, 4 rue de la Chine, 75020, 5 Physiology Laboratory, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France
Correspondence and offprint requests to: Pierre-Louis Tharaux, MD, PhD, INSERM U489 – Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France. Email: pilto{at}bigfoot.com
Background. Sickle cell disease (SCD) affects the kidney by acute mechanisms as well as by insidious renal medullary/papillary necrosis, resulting in tubular defects, which increase the risk of dehydration and subsequent sickle crisis. Hypoxia has been reported to stimulate endothelin-1 (ET-1) synthesis by endothelial cells and also in the renal tubule.
Methods. This case–control study measured ET-1 in urine as a marker of its renal synthesis in asymptomatic SCD patients. Baseline plasma and urinary ET-1 levels were measured and followed during a water deprivation study and a subsequent administration of desmopressin.
Results. Urine and plasma levels of ET-1 were elevated in patients with SCD, compared with carefully matched African-French and African controls, and urine ET-1 excretion was associated with a marked urine-concentrating defect. Moreover, urinary ET-1 output was correlated with microalbuminuria in SCD patients.
Conclusions. ET-1 is known to antagonize the tubular effects of vasopressin and to promote renal scarring; increased renal production of ET-1 could produce nephrogenic diabetes insipidus and dehydration in SCD patients through a combination of fibrosis and functional resistance to vasopressin. This study provides a rationale for trials with endothelin receptor antagonists in sickle cell disease nephropathy.
Keywords: endothelin-1; hypoxia; nephrogenic diabetes insipidus; sickle cell disease
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