Abstract
BackgroundAutosomal 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.MethodsEighty 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).ResultsComparing 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.ConclusionIncreased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.
Highlights
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism
Autosomal dominant polycystic kidney disease (ADPKD) is a congenital progressive disease resulting in chronic kidney disease (CKD) that often progresses to end-stage renal disease (ESRD)
The present study suggests (a) that random bloodsampling in a clinical setting can yield meaningful patterns of miRs, (b) that these patterns vary between healthy subjects and those with kidney disease, and, (c) that increased copy numbers of miR-3907 in the circulation predicts the future decline in Estimated glomerular filtration rate from biochemical data (eGFR) among ADPKD patients followed for 12 months
Summary
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Autosomal dominant polycystic kidney disease (ADPKD) is a congenital progressive disease resulting in chronic kidney disease (CKD) that often progresses to end-stage renal disease (ESRD). In renal tissue miRs have been implicated in both embryonic development and kidney disease processes and altered levels have been reported in the blood and urine during several specific glomerular and tubular diseases as well as in animal models of these [5,6,7,8]. While few studies have investigated miRs in ADPKD, two recent animal experiments have suggested that they may be important as regulators of pro-fibrotic calcium signaling [9, 10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
