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Allograft Rejection and Tubulointerstitial Fibrosis in Human Kidney Allografts: Interrogation by Urinary Cell mRNA Profiling #MMPMID24929703
Muthukumar T; Lee JR; Dadhania DM; Ding R; Sharma VK; Schwartz JE; Suthanthiran M
Transplant Rev (Orlando) 2014[Jul]; 28 (3): 145-54 PMID24929703show ga
Because the kidney allograft has the potential to function as an in-vivo flowcytometer and facilitate the access of immune cells and kidney parenchymal cells in to the urinary space, we hypothesized that mRNA profiling of urinary cells offers a noninvasive means of assessing the kidney allograft status. We overcame the inherent challenges of urinary cell mRNA profiling by developing pre-amplification protocols to compensate for low RNA yield from urinary cells and by developing robust protocols for absolute quantification mRNAs using RT-PCR assays. Armed with these tools, we undertook first single-center studies urinary cell mRNA profiling and then embarked on the multicenter Clinical Trials in Organ Transplantation-04 study of kidney transplant recipients. We report here our discovery and validation of diagnostic and prognostic biomarkers of acute cellular rejection and of interstitial fibrosis and tubular atrophy (IF/TA). Our urinary cell mRNA profiling studies, in addition to demonstrating the feasibility of accurate diagnosis of acute cellular rejection and IF/TA in the kidney allograft, advance mechanistic and potentially targetable biomarkers. Interventional trials, guided by urinary cell mRNA profiles, may lead to personalized immunosuppression in recipients of kidney allografts.