Early Detection Of Renal Injury

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

1) We developed an automated method for quantitating interstitial fibrosis during chronic kidney disease, where we can sample the entire kidney section, rather than selected high power fields of view, and our digital masking of vessel-associated collagen enabled us to remove this quantitative artifact. 2) In a study with mouse sepsis, we found that serum Cystatin C had a faster increase and reached peak levels more rapidly than serum creatinine. Serum creatinine had better performance than Cystatin C at later time points. We were able to develop a composite serum creatinine and serum Cystatin C score that performed well at all time points. Similar to our previous work, we found that cystatin C production was reduced in sepsis. Both serum Cystatin C and serum creatinine outperformed BUN at early prediction of sepsis-induced mortality. 3) We are continuing our work on exosomes as a source of biomarkers, including proteins and miRNA. We are exploring proper normalizing techniques for these biomarkers, including counting exosomes by Nanosight Tracking Analysis and measuring TSG101 by western blot. 4) We are continuing a public-private consortium with the HESI Genomics microRNA Focus Group to compare standard protocol vs site-specific protocols from multiple sites; variations will identify which preanalytical steps affect microRNA detection and quantification in biofluids in drug-induced injury models. The initial model is a cardiotoxin that stimulates release of miRNAs into the circulation, which will shed light on renal handling of miRNA. Urinary miRNA from non-renal sources is expected to be non-exosomal.