The role of microvascular injury on steroid and OKT3 response in renal allograft rejection.

Abstract

The authors' aim is to understand the influence of human leukocyte antigen-DR positive microvascular (MV)-DR destruction on steroid and OKT3 response in acute rejection (AR). Twenty of 40 patients had steroid-resistant AR (group 1) and received OKT3 treatment, and the other 20 patients had AR that responded to steroid treatment (group 2). A renal biopsy specimen was obtained from each subject during the AR episode. The degree of MV-DR destruction and the peritubular capillary (PTC) leukocyte infiltration were recorded in each case, using three-tiered scales. The follow-up biopsy specimens of all cases were evaluated for the development of interstitial fibrosis (IF). Seventy-eight percent of the cases with severe MV destruction and 45% of those with moderate MV destruction did not show response to steroid therapy, whereas 74% of the cases with mild MV destruction responded to steroid therapy. Group 1 patients showed higher frequencies of vascular rejection (80%) and high-grade PTC leukocyte infiltration (85%) than the group 2 cases (P<0.01 for both). Seventy percent of the patients in group 1 responded to OKT3 therapy. The biopsy specimens from the six individuals who were resistant to OKT3 had shown severe MV destruction, vascular rejection, and high-grade PTC leukocyte infiltration. Severity of MV destruction in the initial AR diagnostic biopsy was positively correlated with development of diffuse IF and chronic allograft nephropathy in the follow-up biopsy specimens (P<0.001) Analysis of MV destruction may be helpful for diagnosing rejection and predicting graft prognosis. This type of assessment may be useful for determining the immune response and thus identifying the most appropriate treatment.