Journal Article

Urinary endothelin-1 as a marker of renal damage in sickle cell disease

Pierre-Louis Tharaux, Isabelle Hagège, Sandrine Placier, Michel Vayssairat, Alain Kanfer, Robert Girot and Jean-Claude Dussaule

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 20, issue 11, pages 2408-2413
Published in print November 2005 | ISSN: 0931-0509
Published online September 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfi111
Urinary endothelin-1 as a marker of renal damage in sickle cell disease

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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

Journal Article.  3240 words.  Illustrated.

Subjects: Nephrology

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