The Systems Biology of Clinical Organ Transplantation

13:40 Late Deterioration of Kidney Allograft Function: Preliminary Results from the DeKAF Study
Arthur J. Matas, University of Minnesota, Minneapolis, USA

The Long-term Deterioration of Kidney Allograft Function (DeKAF) study is a multicenter, NIH-funded, observational study conducted at 7 centers in the U.S. and Canada. DeKAF was designed with the premise that late graft dysfunction, if examined early in its course, can be characterized as definable clinical and histopathologic entities with distinct phenotypes. If these phenotypes can be defined, intervention trials for each could be developed. The study consists of 2 cohorts of kidney transplant recipients: a cross-sectional (CS) cohort; and a prospective cohort. The CS cohort provides an overview of the "troubled kidney", irrespective of the time from transplant, and preliminary data from CS cohort are available.

Recipients were eligible for enrollment in this cohort if they had undergone a kidney or kidney-pancreas transplant at any time prior to January 1, 2006, had a serum creatinine level of ≤ 2.0 mg/dl (last creatinine measured) on January 1, 2006, and subsequently developed deterioration of graft function that led to a kidney allograft biopsy. Allograft biopsies were read by the local pathologist, and the pathologic diagnosis was used to guide clinical care and any adjustments to immunosuppressive medications. Clinical care was provided using local protocols.

We found that local pathologist’s diagnoses were not prognostic: CAN vs. no CAN had similar outcome; and CNI toxicity vs. no toxicity had similar outcome. However, cluster analysis based on BANFF scores (individual scores and severity of score) (central pathology) separated recipients into distinct groups (clusters). C4d staining and the presence of donor-specific antibody did not distinguish clusters. Importantly, actuarial outcome (from time of biopsy) differed by cluster, suggesting that phenotypes are being distinguished. This is a first step to developing intervention trials for each phenotype.