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

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

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalTransplantation Reviews
Volume28
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Transplantation

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