Relationship of urinary endothelin-1 with estimated glomerular filtration rate in autosomal dominant polycystic kidney disease: a pilot cross-sectional analysis

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-016-0232-8) contains supplementary material, which is available to authorized users.