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Urinary cell mRNA profiles predictive of human kidney allograft status
Author(s) -
Lee John R.,
Muthukumar Thangamani,
Dadhania Darshana,
Ding Ruchuang,
Sharma Vijay K.,
Schwartz Joseph E.,
Suthanthiran Manikkam
Publication year - 2014
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12159
Subject(s) - kidney transplantation , kidney , biology , urinary system , pathology , transplantation , biopsy , medicine , endocrinology
Summary Kidney allograft status is currently characterized using the invasive percutaneous needle core biopsy procedure. The procedure has become safer over the years, but challenges and complications still exist including sampling error, interobserver variability, bleeding, arteriovenous fistula, graft loss, and even death. Because the most common type of acute rejection is distinguished by inflammatory cells exiting the intravascular compartment and gaining access to the renal tubular space, we reasoned that a kidney allograft may function as an in vivo flow cytometer and sort cells involved in rejection into urine. To test this idea, we developed quantitative polymerase chain reaction ( PCR ) assays for absolute quantification of mRNA and pre‐amplification protocols to overcome the low RNA yield from urine. Here, we review our single center urinary cell mRNA profiling studies that led to the multicenter Clinical Trials in Organ Transplantation ( CTOT ‐04) study and the discovery and validation of a 3‐gene signature of 18S rRNA ‐normalized measures of CD 3ε mRNA and IP‐10 mRNA and 18S rRNA that is diagnostic and predictive of acute cellular rejection in the kidney allograft. We also review our development of a 4‐gene signature of mRNA s for vimentin, NKCC 2, E‐cadherin, and 18S rRNA diagnostic of interstitial fibrosis/tubular atrophy ( IF / TA ).