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

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 micro...

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Autores principales: Kocyigit, Ismail, Taheri, Serpil, Sener, Elif Funda, Eroglu, Eray, Ozturk, Fahir, Unal, Aydin, Korkmaz, Kezban, Zararsiz, Gokmen, Sipahioglu, Murat Hayri, Ozkul, Yusuf, Tokgoz, Bulent, Oymak, Oktay, Ecder, Tevfik, Axelsson, Jonas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450105/
https://www.ncbi.nlm.nih.gov/pubmed/28558802
http://dx.doi.org/10.1186/s12882-017-0600-z
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author Kocyigit, Ismail
Taheri, Serpil
Sener, Elif Funda
Eroglu, Eray
Ozturk, Fahir
Unal, Aydin
Korkmaz, Kezban
Zararsiz, Gokmen
Sipahioglu, Murat Hayri
Ozkul, Yusuf
Tokgoz, Bulent
Oymak, Oktay
Ecder, Tevfik
Axelsson, Jonas
author_facet Kocyigit, Ismail
Taheri, Serpil
Sener, Elif Funda
Eroglu, Eray
Ozturk, Fahir
Unal, Aydin
Korkmaz, Kezban
Zararsiz, Gokmen
Sipahioglu, Murat Hayri
Ozkul, Yusuf
Tokgoz, Bulent
Oymak, Oktay
Ecder, Tevfik
Axelsson, Jonas
author_sort Kocyigit, Ismail
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-017-0600-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-54501052017-06-01 Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function Kocyigit, Ismail Taheri, Serpil Sener, Elif Funda Eroglu, Eray Ozturk, Fahir Unal, Aydin Korkmaz, Kezban Zararsiz, Gokmen Sipahioglu, Murat Hayri Ozkul, Yusuf Tokgoz, Bulent Oymak, Oktay Ecder, Tevfik Axelsson, Jonas BMC Nephrol Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12882-017-0600-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-30 /pmc/articles/PMC5450105/ /pubmed/28558802 http://dx.doi.org/10.1186/s12882-017-0600-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kocyigit, Ismail
Taheri, Serpil
Sener, Elif Funda
Eroglu, Eray
Ozturk, Fahir
Unal, Aydin
Korkmaz, Kezban
Zararsiz, Gokmen
Sipahioglu, Murat Hayri
Ozkul, Yusuf
Tokgoz, Bulent
Oymak, Oktay
Ecder, Tevfik
Axelsson, Jonas
Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
title Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
title_full Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
title_fullStr Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
title_full_unstemmed Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
title_short Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
title_sort serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450105/
https://www.ncbi.nlm.nih.gov/pubmed/28558802
http://dx.doi.org/10.1186/s12882-017-0600-z
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