Despite improved tissue matching and the advent of newer immunosuppression protocols, rejection of the transplanted kidney remains a major hindrance to the successful outcome of kidney transplantation. For patients with 1 or more acute rejection episodes the incidence of graft loss due to chronic rejection at 1, 2, and 3 years is 3, 9, and 12%, respectively. The major objective of this prospective study is to define predictors of allograft outcome following first acute rejection episodes developing the first year following kidney transplantation.
Our specific aims are: 1.) To evaluate the association between kidney biopsy histology obtained 6 weeks after the first acute rejection episode with graft outcome. 2.) To determine if fine needle aspiration can be used to diagnose subclinical acute rejection. 3.) To evaluate the association with graft outcome of graft infiltrating T cells of defined phenotypes (CD4, CD45R, CD8, CD28), function (cytotoxic/proliferative/cytokine production) or specificity (class I/II antigens) evaluated at the 6 week follow-up biopsy. Patients will be admitted to the Clinical Research Center at the University of Minnesota 6 weeks after treatment of their first acute rejection episode. Patients will undergo percutaneous kidney biopsy and biopsy specimens will be evaluated by light (for histology) and immunofluorescence (for T lymphocyte subsets and cytokine expression) microscopy. T cells will be grown from a small portion of the kidney biopsy specimen for cell surface phenotyping and primed lymphocyte testing. Half of the patients will also undergo fine needle aspiration biopsy. Fine needle aspiration cytology will be evaluated by light microscopy for presence or absence of cells consistent with acute rejection. Patient and graft survival rates, as well as chronic rejection rates, will be computed. Rejection episodes will be defined by core needle kidney biopsy and tabulated for each recipient. T cell subsets and T cell cytokines will be correlated with rejection. All patients will be followed for 5 years. The demonstration of an association between graft infiltrating T cells of defined phenotypes and function present at 6 weeks and chronic rejection at 3 years might indicate which individuals with acute rejection on protocol biopsy should be targeted for intensive treatment and monitoring.
Showing the most recent 10 out of 356 publications
