Serum microRNA profiles in patients with autosomal dominant polycystic kidney disease show systematic dysregulation partially reversible by hemodialysis

Beata Małachowska; Marcin Tkaczyk; Sławomir Chrul; Rafał Zwiech; Wojciech Młynarski; Wojciech Fendler

doi:10.5114/aoms.2019.86804

Serum microRNA profiles in patients with autosomal dominant polycystic kidney disease show systematic dysregulation partially reversible by hemodialysis

Arch Med Sci. 2019 Jul 22;17(6):1730-1741. doi: 10.5114/aoms.2019.86804. eCollection 2021.

Authors

Beata Małachowska¹, Marcin Tkaczyk², Sławomir Chrul², Rafał Zwiech³, Wojciech Młynarski⁴, Wojciech Fendler^{1

5}

Affiliations

¹ Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
² Department of Pediatrics, Immunology and Nephrology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
³ Department of Kidney Transplantation/Dialysis Department, Barlicki Memorial Teaching Hospital No. 1, Medical University of Lodz, Lodz, Poland.
⁴ Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
⁵ Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

Introduction: The impact of autosomal dominant polycystic kidney disease (ADPKD) on serum microRNAs (miRNA) is unknown.

Material and methods: For profiling experiment we recruited 30 patients from three equinumerous groups: controls, ADPKD and ADPKD on hemodialysis. From the last group extra samples were collected for in pre-/postdialysis analysis. Additionally, 23 healthy volunteers were used for selected biomarker verification. Real-time PCR arrays were used for quantification of 752 miRNAs. Validation of selected miRNAs was performed in total RNA extracted from the serum and the exosomal fraction in pre-/postdialysis samples.

Results: In total, 37 significant circulating miRNAs were found to differ between ADPKD patients and controls. In validation, 3 miRNAs with the highest fold change in comparison of dialyzed vs non-dialyzed patients (miR-532-3p, miR-320b, miR-144-5p) were not significantly altered by hemodialysis and from the top down-regulated ones, miR-27a-3p was significantly lower after dialysis in both total and exosomal fractions, miR-20a-5p was down-regulated in the exosomal fraction and miR-16-5p was unaltered by hemodialysis. MiR-16-5p was selected as the best circulating biomarker of ADPKD. Circulating representatives of the miR-17 family sharing the same seed region (miR-20a-5p, miR-93-5p and miR-106a-5p) showed significantly lower expression among dialyzed vs. non-dialyzed patients and their exosomal fraction dropped after hemodialysis.

Conclusions: The serum miRNAs among ADPKD patients differ substantially depending on the stage of CKD. The exosomal fraction of miRNA was more affected by dialysis than the total one. There was a common pattern of down-regulation for circulating miR-17 family members sharing the same seed region.

Keywords: autosomal dominant polycystic kidney disease; chronic kidney disease; exosomes; hemodialysis; microRNA expression; serum.