Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a life-long disease in which the genes responsible are known, but the pathogenesis of cyst formation and cyst growth are not understood. Cyst growth ultimately leads to end stage renal failure in most patients. Analysis of the urinary proteome offers the potential to identify proteins that indicate the presence of cysts (and thus provides diagnosis) as well as the rates of cyst growth (providing prognostic information).
We performed scheduled Parallel Reaction Monitoring (sPRM) assay on urine samples from 14 patients and 18 normal controls. For relative quantification, we spiked stable isotope-labeled synthetic peptides in the urinary protein digests prior to data collection. The data were subsequently normalized to creatinine and protein concentration in the respective urine samples to control for variations in water intake between individuals.
We show that 69 of the targeted urinary proteins are significantly dysregulated in ADPKD, and can be used to cluster ADPKD patients into those who are more or less similar to normal controls.
Our study shows that sPRM is a promising approach to rapidly screen large numbers of proteins in urine in order to provide earlier diagnosis and potentially better understand the pathogenesis of ADPKD development and progression. This article is protected by copyright. All rights reserved.
Proteomics. Clinical applications. 2018 Mar 23 [Epub ahead of print]
Navin Rauniyar, Xiaoqing Yu, Jennifer Cantley, Edward Voss, Justin Belcher, Chris Colangelo, Kathryn Stone, Neera Dahl, Chirag Parikh, TuKiet T Lam, Lloyd G Cantley
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA., Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA., MS & Proteomics Resource, W.M. Keck Biotechnology Resource Laboratory, Yale University School of Medicine, New Haven, CT, USA.