JI Program: Renal
Chronic kidney disease (CKD) is a significant public health problem, and progression to end-stage renal disease (ESRD) leads to dramatic increases in morbidity and mortality. The mechanisms underlying progression of CKD are poorly defined, and current noninvasive markers incompletely correlate with disease progression. In this discovery proposal, we seek to discover global glycoprotein profiles that predict progression and we will explore specific glycosylation changes to UMOD that associates with progression. We propose to set up a case control discovery study from our existing biobank with 100 subjects at Peking University First Hospital. Utilizing shotgun glycoproteomics, we will determine urinary glycoprotein markers for progression. These discovery studies will lay the groundwork for future large-scale studies to identify biomarker potential of the identified markers. This work will establish a collaborative infrastructure between PUHSC and Michigan Medicine and foster training opportunities for PUHSC graduate students in renal glycoproteomics.
- 100 urine samples (50 IgA and 50 DKD) samples were collected in PKUHSC biorepository and shipped to Michigan Medicine. 100 samples were collected for the mass spectrometric analyses.
- 1 PhD student from PKUHSC received extensive training at Michigan Medicine mentored by Dr. Pennathur.
- Urine succinate and citrate predict pregression of kidney disease in the U.S. cohort. If confirmed in the PKUHSC cohort, these biomarkers could be used for prediction for DKD progression.
- The rodent studies are ongoing with development of rat diabetic kidney disease model in both wild type and THP null rats. Once completed (in summer 2019), these samples will be shipped to UM for metabolomics analysis. These studies will be pivotal in providing the mechanistic link between THP and mitochondrial nutrient metabolism and risk for DKD progression.
Manuscript in preparation