Urinary endothelin-1 as a marker of renal damage in sickle cell disease.
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.
Tharaux
Pierre-Louis
PL
INSERM U702 - Hôpital Tenon, 75020 Paris, France. pilto@bigfoot.com
Hagège
Isabelle
I
Placier
Sandrine
S
Vayssairat
Michel
M
Kanfer
Alain
A
Girot
Robert
R
Dussaule
Jean-Claude
JC
D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology / Q000652:urine*; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D018500:Diabetes Insipidus, Nephrogenic / Q000097:blood / Q000150:complications / Q000652:urine*; D018450:Disease Progression; D019332:Endothelin-1 / Q000096:biosynthesis / Q000097:blood / Q000652:urine*; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D012720:Severity of Illness Index
D015415:Biomarkers; D019332:Endothelin-1