Urinary endothelin-1 as a marker of renal damage in sickle cell disease
PL Tharaux, I Hagège, S Placier… - Nephrology Dialysis …, 2005 - academic.oup.com
PL Tharaux, I Hagège, S Placier, M Vayssairat, A Kanfer, R Girot, JC Dussaule
Nephrology Dialysis Transplantation, 2005•academic.oup.comBackground. 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 …
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 …
Abstract
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.
Oxford University Press