The association of endothelin-1 levels with renal survival in polycystic kidney disease patients

Abstract

Background

The prominent features of autosomal dominant polycystic kidney disease (ADPKD) are early development of hypertension, chronic kidney disease and cardiovascular problems. Thus, we aimed to investigate the role of endothelin, a vascular biomarker, in the clinical course of ADPKD, including renal and cardiovascular survival.

Methods

In 138 patients with ADPKD and 28 healthy controls, we measured serum endothelin-1 (ET-1) levels by enzyme-linked immunosorbent assay (ELISA). Endothelium-dependent vasodilatation (flow-mediated dilatation, FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation, NMD) of the brachial artery were assessed non-invasively with high-resolution ultrasound. Magnetic resonance imaging (MRI) was performed with a 1.5-T system, and total kidney volumes were calculated using mid-slice technique. To determine PKD1 and PKD2 genotype, we performed molecular and genetic tests involving the following steps: DNA isolation, next-generation sequencing (NGS) and data analysis.

Results

Endothelin levels and height-adjusted total kidney volumes (hTKV) significantly increased while the estimated glomerular filtration rate (eGFR) decreased across CKD stages 1–4. Hypertension was more frequent in ADPKD patients with high serum endothelin. At multivariate Cox analysis, endothelin level, PKD1 truncating mutation, hTKV, high-sensitive C reactive protein (hs-CRP) level and the presence of diabetes mellitus were associated with the risk of overall survival. Moreover, endothelin level, PKD1 truncating mutation, hTKV, age and presence of hypertension were associated with the risk of renal survival. Additionally, body mass index (BMI), FMD, PKD1 truncating mutation, endothelin and triglyceride levels were independently associated with hypertension.

Conclusions

Increased serum endothelin levels independently predict hypertension in ADPKD. Serum endothelin levels are also associated with both renal and overall survival in patients with ADPKD.

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Acknowledgements

We thank to the all study participants who enrolled to the study.

Funding

There is no funding of the study.

Author information

Affiliations

Authors

Contributions

IK, EE, ASK and GZ conceived of the study and designed the protocol which was implemented by IK, EE, MHS and BT. These authors also recruited the participants. MD, OO helped with the study design. HI performed the assessments of total kidney volume. DK and RB set up and validated the endothelin assay and helped to interpret the results. IK and EE coordinated the study. All authors participated in data analysis and interpretation, and also read and approved the final manuscript.

Corresponding author

Correspondence to Eray Eroglu.

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Conflict of interest

All authors declare that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Cite this article

Kocyigit, I., Eroglu, E., Kaynar, A.S. et al. The association of endothelin-1 levels with renal survival in polycystic kidney disease patients. J Nephrol 32, 83–91 (2019). https://doi.org/10.1007/s40620-018-0514-2

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Keywords

  • Endothelin
  • Biomarkers
  • CKD
  • Endothelial dysfunction
  • ADPKD