Subclinical Inflammation in Renal Transplantation

The standardization of renal allograft pathology began in 1991 at the first Banff Conference held in Banff, Alberta, Canada. The first task of transplant pathologists, clinicians, and surgeons was to establish diagnostic criteria for T-cell-mediated rejection (TCMR). The histological threshold for this diagnosis was arbitrarily set at "i2t2": a mononuclear interstitial cell infiltrate present in at least 25% of normal parenchyma and >4 mononuclear cells within the tubular basement membrane of nonatrophic tubules. TCMR was usually found in dysfunctional grafts with an elevation in the serum creatinine; however, our group and others found this extent of inflammation in "routine" or "protocol" biopsies of normally functioning grafts: "subclinical" TCMR. The prevalence of TCMR is higher in the early months posttransplant and has decreased with the increased potency of current immunosuppressive agents. However, the pathogenicity of lesser degrees of inflammation under modern immunosuppression and the relation between ongoing inflammation and development of donor-specific antibody has renewed our interest in subclinical alloreactivity. Finally, the advances in our understanding of pretransplant risk assessment, and our increasing ability to monitor patients less invasively posttransplant, promises to usher in the era of precision medicine.