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

BMC Nephrology

Research Article

Bruce Berger¹  Angelique Sao-Mai Do¹  Michael Simonson¹  Rupesh Raina²  Beth Vogt²  Linda Lou²  Robert Cunningham²  Karin Herrmann³  Pauravi Vasavada³  Katherine Dell⁴ 

[1] Department of Medicine, Division of Nephrology and Hypertension, Cleveland, USA;Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, 44106, Cleveland, OH, USA;Department of Pediatrics, Division of Pediatric Nephrology, Rainbow Babies and Children’s Hospital, Cleveland, USA;Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, 44106, Cleveland, OH, USA;Department of Radiology, Cleveland, USA;Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, 44106, Cleveland, OH, USA;University Hospitals Case Medical Center, Center for Pediatric Nephrology, Cleveland Clinic Foundation, Cleveland, USA;Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, 44106, Cleveland, OH, USA;

关键词: Autosomal dominant polycystic kidney disease;    Endothelin-1;    Cyst growth;    Hypertension;    Kidney volume;   

DOI  :  10.1186/s12882-016-0232-8

 received in 2015-03-26, accepted in 2016-02-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsIn 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.ResultsPatients 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.ConclusionsIn 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.

【 授权许可】

CC BY   
© Raina et al. 2016