Abstract Title: STUDY OF mRNAs IN URINE SAMPLES OF KIDNEY TRANSPLANT RECIPIENTS AS INDICATORS OF ALLOGRAFT FUNCTION
Valeria Mas, PhD1, Luciana Mas, MS1-2, Robert Fisher, MD1, Kellie Archer, PhD3, Kenneth Yanek, MS1, Anne King, MD1, Eric Gibney, MD1, Adrian Cotterell, MD1, Marc Posner, MD1 and Daniel Maluf, MD1. 1Surgery, Virginia Commonwealth University, Richmond, VA, United States; 2Hospital Privado, Cordoba, Argentina and 3Biostatistics, VCU, Richmond, VA, United States.
Body: Background. There is evidence that monitoring in urine cells may be useful in the early period after kidney transplant (KT), particularly in relation to predicting the presence of acute rejection (AR). It is less clear whether chronic allograft nephropathy (CAN) is also associated with consistent changes in urine cells. To identify non-invasive markers of allograft function in kidney transplant recipients (KTR), we studied mRNA levels of AGT, TGF-1, EGFR, IFN-, thrombospondin-1 (TSP-1), and IL-10 in urine (Ur) samples.
Patients and Methods. Ninety-five KTR, (follow-up time= 22.922.1 months (mo), range= 1-60) and 111 Ur were evaluated. Gene expression levels were studied using qRT-PCR. 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 KTR with stable kidney function (SKF) (N=32), KTR with SKF (creatinine <2 mg/dl) and proteinuria >500mg/24hs (N=18), and KTP with biopsy proven CAN (N=14). F-test was used for equality of variances between groups. Variables with significantly different variances among groups were then compared using a two sample t-test using Satterthwaites adjustment to the degrees; otherwise, a two-sample t-test was applied.
Results. IFN- mRNA levels were significantly higher in KTR with less than 6 mo post-KT and associated with AR episodes (P=0.042). IL-10 mRNA levels were decreased in this group (P=0.005). Among the different KTR groups with more than 6 mo post-KT, mRNA levels of AGT and EGFR were statistically lower in KTP with SKF and proteinuria and in CAN Pts when compared to KTP with SKF (P=0.003, and P=0.001; respectively). EGFR mRNA were differentially expressed between KTP with SKF and proteinuria vs. CAN Pts (P=0.05). TGF-1 and TSP-1 mRNA levels were significantly higher in CAN Pts (P=0.029 and P=0.04). AR episodes were significantly higher in CAN patients (P=0.02). However, there was no statistically significant difference for BK, CMV, age, type of donor, cold and warm ischemia time.
Conclusions. Ur samples represent a good source for monitoring mRNA levels in KTR. We found a characteristic pattern of mRNA levels KTR with SKF, KTP with SKF and proteinuria, and CAN Pts indicating that the mRNA levels in Ur cells might reflect allograft function.