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- Title
Relationship of urinary endothelin-1 with estimated glomerular filtration rate in autosomal dominant polycystic kidney disease: a pilot cross-sectional analysis.
- Authors
Raina, Rupesh; Lou, Linda; Berger, Bruce; Vogt, Beth; Sao-Mai Do, Angelique; Cunningham, Robert; Vasavada, Pauravi; Herrmann, Karin; Dell, Katherine; Simonson, Michael; Do, Angelique Sao-Mai
- Abstract
<bold>Background: </bold>The pathogenesis of progressive renal insufficiency in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Evidence from experimental models of ADPKD suggests that elevated endothelin-1 (ET-1) drives cyst growth, renal fibrosis and loss of renal function, but whether ET-1 is elevated in humans with ADPKD is uncertain.<bold>Methods: </bold>In a cross-sectional study of ADPKD we measured urinary ET-1, a surrogate for ET-1 in kidney cortex, in spot collections corrected for creatinine. The volume of each kidney was measured using MRI-based stereology. The relationship of urine ET-1 with MDRD eGFR and kidney volume was modeled by multiple linear regression with adjustment for clinical covariates.<bold>Results: </bold>Patients with ADPKD were ages 18 to 53 with eGFRs (median, interquartile range) of 63.2 (43.5-80.2) ml/min/1.73 m(2) and albumin/creatinine ratios (ACR) of 115.0 (7.5-58.5) μg/mg. Urine ET-1 was inversely associated with eGFR (r = -0.480, P < 0.05) and positively (r = 0.407, P = 0.066) with ACR independent of age and female sex (P < 0.01). ET-1 appeared to be positively associated with total kidney volume (r = 0.426, P = 0.100), with a test for trend across urine ET-1 quartiles yielding z = 1.83, P = 0.068. ET-1 strongly correlated with NAGase (r = 0. 687, P = 0.001), a marker of tubular damage and a surrogate marker of renal disease progression in ADPKD. Of note, ET-1 levels in urine were not correlated with hypertension.<bold>Conclusions: </bold>In a translational study of patients with ADPKD, urinary ET-1 was inversely associated with eGFR and positively correlated with total kidney volume. Taken together with results from experimental models, these findings suggest that the role of ET-1 in ADPKD warrants further investigation.
- Subjects
POLYCYSTIC kidney disease; PREPROENDOTHELIN; KIDNEY tumors; HYPERTENSION risk factors; RENAL fibrosis; CROSS-sectional method; GENETICS; ANTHROPOMETRY; ENDOTHELINS; GLOMERULAR filtration rate; GLYCOSIDASES; HYPERTENSION; KIDNEYS; MAGNETIC resonance imaging; KIDNEY failure; PILOT projects; SEVERITY of illness index; DISEASE progression
- Publication
BMC Nephrology, 2016, Vol 17, p1
- ISSN
1471-2369
- Publication type
journal article
- DOI
10.1186/s12882-016-0232-8