LONG-TERM DETERIORATION OF KIDNEY ALLOGRAFT FUNCTION (DEKAF)

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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. The two major problems in clinical kidney transplantation (ktx) today are late graft loss (LGL) and the shortage of organs. In fact, these problems are interrelated - ktx failure is currently the 3rd leading cause of end stage renal disease (ESRD) in the U.S. and recipients returning to the waiting list contribute to the organ shortage. For the past decade it was hoped that decreasing the incidence of acute rejection (AR) would reduce LGL. In fact, the use of modern immunosuppression has decreased AR rates during the last year post-ktx to <10% at many centers; this has been associated with improvement in long-term function (the slope of the GFR) has also improved, perhaps related to superior control of rejection with newer protocols. Despite these advances, LGL continues to be a problem: almost 4,500 ktx recipients returned to dialysis in 2003, most of them late (>1 year post-tx). Furthermore, improvements in graft survival have plateaued. Thus, we have improved AR rates and early outcomes but LGL remains a problem; our previous conceptualization provides an inadequate basis for effective intervention. The long-term goal of this study is to understand and reduce long-term ktx deterioration. The specific aims of the study are to 1) determine, in a previously ktx cross-sectional cohort, whether clinical, laboratory, or pathologic studies at the time of initial graft dysfunction define clinico-pathologic entitites; 2) determine, in a prospective cohort, whether clinical, laboratory, and pathologic studies at the time of initial graft dysfunction define different entitites; and 3) determine whether markers of fibrogenic activity and/or inflammation, the presence of anti-human leukocyte antigen antibodies, or other clinical correlates can define the probability of progression and the rate of progression of chronic graft dysfunction.