Evaluation of Gene Panel mRNAs in Urine Samples of Kidney Transplant Recipients as a Non-invasive Tool of Graft Function

Abstract

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-β1, EGFR, IFN-γ, 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 six months (N = 31), and with more than six months post-KT (N = 64). KTP with more than six months post-KT were classified as KTP with stable kidney function (SKF) (N = 32), KTP with SKF (creatinine < 2 mg/dL) and proteinuria > 500 mg/24 h (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 six months post-KT (P = 0.005). For KTR groups with more than six months 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 also were 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-β1 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.

The urine microRNA profile may help monitor post-transplant renal graft function

“…The evaluation of mRNA in urinary cells has been a common approach during the last years for evaluating native and allograft kidneys (22-26, 33-35). However, most of the urine samples have total RNA without the required concentration, and/or quality and integrity for microarray analysis.…”

Noninvasive Prediction of Organ Graft Rejection and Outcome Using Gene Expression Patterns

“…In kidney transplantation, the progressive scaring process of the allograft, formerly called “chronic allograft nephropathy”, which is secondary to a number of contributory factors such as immunological insults, hemodynamic changes, and calcineurin inhibitor nephrotoxicity, remains the chief cause of kidney transplant failure (47). Recent data suggest that differential expression of a number of transcripts in urinary cells could be a valuable biomarker of chronic allograft nephropathy (48–50). Several laboratories are developing noninvasive tools to molecularly define subgroups of chronic allograft nephropathies (e.g.…”

A New Clinical Prediction Tool for 5-Year Kidney Transplant Outcome

“…Novel biomarkers also have shown some promise in predicting long-term transplant outcome. 16,17 However, to date, these markers, many of which require specialized laboratory testing, have not proved attractive enough to warrant widespread adoption.…”