Academic Commons

Articles

Allograft rejection and tubulointerstitial fibrosis in human kidney allografts: Interrogation by urinary cell mRNA profiling

Muthukumar, Thangamani; Lee, John R.; Dadhania, Darshana M.; Ding, Ruchuang; Sharma, Vijay K.; Schwartz, Joseph E.; Suthanthiran, Manikkam

Because the kidney allograft has the potential to function as an in-vivo flow cytometer 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.

Files

  • thumnail for Muthukumar_Transplant_Rev_2014_PMC.pdf Muthukumar_Transplant_Rev_2014_PMC.pdf application/pdf 880 KB Download File

Also Published In

Title
Transplantation Reviews
DOI
https://doi.org/10.1016/j.trre.2014.05.003

More About This Work

Academic Units
Center for Behavioral Cardiovascular Health
Published Here
July 24, 2016