URINARY CELL MRNA PROFILES OF REJECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Clinical acute rejection, defined as a sudden deterioration in renal-allograft function as a result of the recipient's immune response to the donor organ, is a major risk factor for allograft failure. An increase in the serum creatinine level is often the first clinical indicator, and currently the best surrogate marker of acute rejection. This marker lacks sensitivity and specificity. We will test the hypothesis that urinary cell mRNA profiles identify allografts at risk for progressive decline in renal function. Urinary cell mRNA profiling will be performed at pre-defined time points in year one of transplantation. Renal function will be assessed by measuring serum creatinine levels at 12, 24, and 36 months following renal transplantation and estimating GFR with MDRD equation. We are proposing to measure levels of mRNA for perforin, granzyme B and CD3 in urinary cells obtained during the first 12 months after transplantation. Our recent studies suggest that noninvasive diagnosis of acute rejection of renal allografts is feasible by measurement of mRNA for perforin, granzyme B, and CD3 with a specificity of 95% and sensitivity of 95%. Data must be validated in a prospective multicenter trial prior to its application as a routine assay in the clinical setting. The study will demonstrate whether this molecular profiling is predictive and diagnostic, reliable and portable for all transplant centers in the country; whether urinary PCR profile can prognosticate and/or diagnose the occurrence of acute rejection; and whether the results are independent of the type of induction and maintenance immunosuppression.