NDT Advance Access published online on September 6, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi111
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1 INSERM U702, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France
* To whom correspondence should be addressed. 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.
Received December 1, 2004
Accepted June 15, 2005
Original Articles
Urinary endothelin-1 as a marker of renal damage in sickle cell disease
2 Department of Day Hospitalization, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France
3 Department of Vascular Medicine, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France
4 Hematology Laboratory; Tenon Hospital, 4 rue de la Chine, 75020, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France
5 INSERM U702, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France; Physiology Laboratory, Saint-Antoine University Hospital, University Pierre and Marie Curie, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France
Pierre-Louis Tharaux, E-mail: pilto{at}bigfoot.com
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