Chronic kidney disease (CKD) is estimated to affect over 13% of US adults and is increasing in prevalence. More than 76% of CKD cases are caused by glomerular diseases with progressive glomerulosclerosis lesions, including diabetic nephropathy (37%), hypertensive nephropathy (24%), and glomerulonephritis (15%) (www.usrds.org).
We are currently investigating the cell-type specific responses and signals of glomerular disease progression in CKD. In particular we are examining the signaling crosstalk between podocytes, endocapillary cells and mesangial cells that lead to irreversible segmental sclerosis characteristic of glomerular disease progression. This research aims to identify novel glomerular lesion-specific therapeutic targets. We are also interested in understanding the underlying genetic risks for developing CKD in various mouse strains, and this research effort has so led to the discovery of DNA variants linked to the regulation of XOR and production of ROS in a diabetic setting and aging.
As part of the CKD Biomarkers Consortium(http://www.ckdbiomarkersconsortium.org/) we were involved in screening kidney tissue damage markers identified by cross-species (mouse-human) transcriptional profiling in human and murine kidney disease in urine of non-renal controls, ‘non-progressive’ and ‘rapid progressive’ CKD cases (Mount Sinai CKD cohort). Using an innovative “virtual clinical cohort” approach we will then analyze the candidate biomarkers for clinical utility using biospecimens collected during routine clinical care and clinical data culled from the electronic medical record.