Evaluation of Gene Panel cnRNAs in Urine Samples of Kidney Transplant Recipients as a Non-invasive Tool of Graft Function.
Molecular medicine (Cambridge, Mass.) 2007 Jun 11; In press
Mas V VR, Mas L LA, Archer K KJ, Yanek K K, King A AL, Gibney E EM,
Division of Transplant, Department of Surgery.
Non-invasive monitoring may be useful after kidney transplantation (KT), particularly for predicting acute rejection (AR). It is less clear whether chronic allograft nephropathy (CAN) is also associated with changes in urine cells. To identify non-invasive markers of allograft function in kidney transplant patients (KTP), mRNA levels of AGT, TGF-beta1, EGFR, IFN-gamma, TSP-1, and IL-10 in urine (Ur) samples were studied using QRT-PCR. Ninety-five KTP and 111 Ur samples were evaluated. Patients (Pts) were divided as, within 6 mo (N=31), and with more than 6 mo post-KT (N=64). KTP with more than 6 mo post-KT were classified as KTP with stable kidney function (SKF) (N=32), KTP with SKF (creatinine <2 mg/dl) and proteinuria >500mg/24hs (N=18), and KTP with biopsy proven CAN (N=14). F-test was used to test for equality of variances between groups. IL-10 mRNA was decreased in Ur samples from KTP with less than 6 mo post-KT (P=0.005). For KTR groups with more than 6 mo post-KT, AGT and EGFR mRNA were statistically different among KTP with SKF, KTP with SKF and proteinuria, and CAN Pts (P=0.003, and P=0.01), with KTP with SKF having higher mean expression. TSP-1 mRNA levels were also significantly different among these three groups (P=0.04), with higher expression observed in CAN Pts. Using the random forest algorithm, AGT, EGFR, and TGF-beta1 were identified as predictors of CAN, SKF, SKF with proteinuria. A characteristic pattern of mRNA levels in the different KTP groups was observed indicating that the mRNA levels in Ur cells might reflect allograft function.