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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Nephrology 1/2016

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

Zeitschrift:
BMC Nephrology > Ausgabe 1/2016
Autoren:
Rupesh Raina, Linda Lou, Bruce Berger, Beth Vogt, Angelique Sao-Mai Do, Robert Cunningham, Pauravi Vasavada, Karin Herrmann, Katherine Dell, Michael Simonson
Wichtige Hinweise

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.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

RR, LL, BB, BV, RC and KD recruited participants. PV and KH analyzed MRI images. ASD and MSS performed statistical analysis, and all authors wrote the manuscript and provided critical review. All authors read and approved the final manuscript.

Abstract

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 m2 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.
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