Skip to main content
Top
Published in: BMC Nephrology 1/2017

Open Access 01-12-2017 | Research article

Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function

Authors: Ismail Kocyigit, Serpil Taheri, Elif Funda Sener, Eray Eroglu, Fahir Ozturk, Aydin Unal, Kezban Korkmaz, Gokmen Zararsiz, Murat Hayri Sipahioglu, Yusuf Ozkul, Bulent Tokgoz, Oktay Oymak, Tevfik Ecder, Jonas Axelsson

Published in: BMC Nephrology | Issue 1/2017

Login to get access

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD.

Methods

Eighty ADPKD patients (44.6 ± 12.7 years, 40% female, 65% hypertensive) and 50 healthy subjects (HS; 45.4 ± 12.7, 44% female) were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.01 considered significant).

Results

Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months (cut-off >2.2 AU, sensitivity 83%, specificity 78%, area 0.872 [95% CI: 0.790–0.953, p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value.

Conclusion

Increased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.
Appendix
Available only for authorised users
Literature
1.
go back to reference Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369(9569):1287–301.CrossRefPubMed Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369(9569):1287–301.CrossRefPubMed
3.
go back to reference Grantham JJ, et al. Volume Progression in Polycystic Kidney Disease. N Engl J Med. 2006;354(20):2122–30.CrossRefPubMed Grantham JJ, et al. Volume Progression in Polycystic Kidney Disease. N Engl J Med. 2006;354(20):2122–30.CrossRefPubMed
4.
go back to reference Wing MR, et al. Epigenetics of Progression of Chronic Kidney Disease: Fact or Fantasy? Semin Nephrol. 2013;33(4):363–74.CrossRefPubMed Wing MR, et al. Epigenetics of Progression of Chronic Kidney Disease: Fact or Fantasy? Semin Nephrol. 2013;33(4):363–74.CrossRefPubMed
5.
go back to reference Ben-Dov IZ, et al. Urine MicroRNA as Potential Biomarkers of Autosomal Dominant Polycystic Kidney Disease Progression: Description of miRNA Profiles at Baseline. PLoS One. 2014;9(1):e86856.CrossRefPubMedPubMedCentral Ben-Dov IZ, et al. Urine MicroRNA as Potential Biomarkers of Autosomal Dominant Polycystic Kidney Disease Progression: Description of miRNA Profiles at Baseline. PLoS One. 2014;9(1):e86856.CrossRefPubMedPubMedCentral
7.
go back to reference Liep J, et al. Cooperative Effect of miR-141-3p and miR-145-5p in the Regulation of Targets in Clear Cell Renal Cell Carcinoma. PLoS One. 2016;11(6):e0157801.CrossRefPubMedPubMedCentral Liep J, et al. Cooperative Effect of miR-141-3p and miR-145-5p in the Regulation of Targets in Clear Cell Renal Cell Carcinoma. PLoS One. 2016;11(6):e0157801.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Pandey P, et al. Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease. BMC Genomics. 2008;9(1):624.CrossRefPubMedPubMedCentral Pandey P, et al. Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease. BMC Genomics. 2008;9(1):624.CrossRefPubMedPubMedCentral
10.
go back to reference Pandey P, et al. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol. 2011;5(1):56.CrossRefPubMedPubMedCentral Pandey P, et al. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol. 2011;5(1):56.CrossRefPubMedPubMedCentral
11.
go back to reference Smyth GK. An efficient algorithm for REML in heteroscedastic regression. J Comput Graph Stat. 2002;11(4):836–47.CrossRef Smyth GK. An efficient algorithm for REML in heteroscedastic regression. J Comput Graph Stat. 2002;11(4):836–47.CrossRef
13.
go back to reference Kocyigit I, et al. Early Arterial Stiffness and Inflammatory Bio-Markers in Normotensive Polycystic Kidney Disease Patients. Am J Nephrol. 2012;36(1):11–8.CrossRefPubMed Kocyigit I, et al. Early Arterial Stiffness and Inflammatory Bio-Markers in Normotensive Polycystic Kidney Disease Patients. Am J Nephrol. 2012;36(1):11–8.CrossRefPubMed
14.
go back to reference Agarwal V, et al. Predicting effective microRNA target sites in mammalian mRNAs. elife. 2015;4 Agarwal V, et al. Predicting effective microRNA target sites in mammalian mRNAs. elife. 2015;4
15.
go back to reference Sammels E, et al. Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J Biol Chem. 2010;285(24) doi:10.1074/jbc.M109.090662. Sammels E, et al. Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J Biol Chem. 2010;285(24) doi:10.​1074/​jbc.​M109.​090662.
16.
go back to reference Devogelaere B, et al. The complex regulatory function of the ligand-binding domain of the inositol 1,4,5-trisphosphate receptor. Cell Calcium. 2008;43(1):17–27.CrossRefPubMed Devogelaere B, et al. The complex regulatory function of the ligand-binding domain of the inositol 1,4,5-trisphosphate receptor. Cell Calcium. 2008;43(1):17–27.CrossRefPubMed
17.
go back to reference Lee S-O, et al. MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Investig. 2008;118(11):3714–24.CrossRefPubMedPubMedCentral Lee S-O, et al. MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Investig. 2008;118(11):3714–24.CrossRefPubMedPubMedCentral
18.
go back to reference Sun H, et al. MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation. Mol Biol Rep. 2009;37(6):2951–8.CrossRefPubMed Sun H, et al. MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation. Mol Biol Rep. 2009;37(6):2951–8.CrossRefPubMed
19.
go back to reference Harskamp LR, et al. The epidermal growth factor receptor pathway in chronic kidney diseases. Nat Rev Nephrol. 2016;12(8):496–506.CrossRefPubMed Harskamp LR, et al. The epidermal growth factor receptor pathway in chronic kidney diseases. Nat Rev Nephrol. 2016;12(8):496–506.CrossRefPubMed
20.
go back to reference Stocklin E. An activated allele of the c-erbB-2 oncogene impairs kidney and lung function and causes early death of transgenic mice. J Cell Biol. 1993;122(1):199–208.CrossRefPubMed Stocklin E. An activated allele of the c-erbB-2 oncogene impairs kidney and lung function and causes early death of transgenic mice. J Cell Biol. 1993;122(1):199–208.CrossRefPubMed
21.
23.
go back to reference Aguado-Fraile E, et al. A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury. PLoS One. 2015;10(6):e0127175.CrossRefPubMedPubMedCentral Aguado-Fraile E, et al. A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury. PLoS One. 2015;10(6):e0127175.CrossRefPubMedPubMedCentral
24.
go back to reference Salih M, et al. Urinary extracellular vesicles as markers to assess kidney sodium transport. Curr Opin Nephrol Hypertens. 2016;25(2):67–72.CrossRefPubMed Salih M, et al. Urinary extracellular vesicles as markers to assess kidney sodium transport. Curr Opin Nephrol Hypertens. 2016;25(2):67–72.CrossRefPubMed
Metadata
Title
Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
Authors
Ismail Kocyigit
Serpil Taheri
Elif Funda Sener
Eray Eroglu
Fahir Ozturk
Aydin Unal
Kezban Korkmaz
Gokmen Zararsiz
Murat Hayri Sipahioglu
Yusuf Ozkul
Bulent Tokgoz
Oktay Oymak
Tevfik Ecder
Jonas Axelsson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2017
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-017-0600-z

Other articles of this Issue 1/2017

BMC Nephrology 1/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.