Identification of biomarkers for PKD1 using urinary exosomes

Marie C Hogan, Jason L. Bakeberg, Vladimir G. Gainullin, Maria Irazabal Mira, Amber J. Harmon, John C Lieske, M. Cristine Charlesworth, Kenneth L. Johnson, Benjamin J. Madden, Roman M. Zenka, Daniel J Mc Cormick, Jamie L. Sundsbak, Christina M. Heyer, Vicente Torres, Peter C Harris, Christopher J. Ward

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of ESRD. Affected individuals inherit a defective copy of either PKD1 or PKD2, which encode polycystin-1 (PC1) or polycystin-2 (PC2), respectively. PC1 and PC2 are secreted on urinary exosome-like vesicles (ELVs) (100-nm diameter vesicles), in which PC1 is present in a cleaved form and may be complexed with PC2. Here, label-free quantitative proteomic studies of urine ELVs in an initial discovery cohort (13 individuals with PKD1 mutations and 18 normal controls) revealed that of 2008 ELV proteins, 9 (0.32%) were expressed at significantly different levels in samples from individuals with PKD1 mutations compared to controls (P,0.03). In samples from individuals with PKD1 mutations, levels of PC1 and PC2 were reduced to 54% (P,0.02) and 53% (P,0.001), respectively. Transmembrane protein 2 (TMEM2), a protein with homology to fibrocystin, was 2.1-fold higher in individuals with PKD1 mutations (P,0.03). The PC1/TMEM2 ratio correlated inversely with height-adjusted total kidney volume in the discovery cohort, and the ratio of PC1/TMEM2 or PC2/TMEM2 could be used to distinguish individuals with PKD1 mutations from controls in a confirmation cohort. In summary, results of this study suggest that a test measuring the urine exosomal PC1/TMEM2 or PC2/TMEM2 ratio may have utility in diagnosis and monitoring of polycystic kidney disease. Future studies will focus on increasing sample size and confirming these studies. The data were deposited in the ProteomeXchange (identifier PXD001075).

Original languageEnglish (US)
Pages (from-to)1661-1670
Number of pages10
JournalJournal of the American Society of Nephrology
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2015

    Fingerprint

ASJC Scopus subject areas

  • Nephrology

Cite this

Hogan, M. C., Bakeberg, J. L., Gainullin, V. G., Irazabal Mira, M., Harmon, A. J., Lieske, J. C., Charlesworth, M. C., Johnson, K. L., Madden, B. J., Zenka, R. M., Mc Cormick, D. J., Sundsbak, J. L., Heyer, C. M., Torres, V., Harris, P. C., & Ward, C. J. (2015). Identification of biomarkers for PKD1 using urinary exosomes. Journal of the American Society of Nephrology, 26(7), 1661-1670. https://doi.org/10.1681/ASN.2014040354