Trends and Characteristics in Early Glomerular Filtration Rate Decline After Posttransplantation Alloantibody Appearance

Abstract

Approximately 7% to 9% of patients with donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) fail within 1 year post-DSA onset. However, little is known as to how this DSA-associated failure temporally progresses. This longitudinal study investigates DSA's temporal relationship to allograft dysfunction and identifies predictors of allograft function's progressive deterioration post-DSA. A cohort of 175 non-HLA identical patients receiving their first transplant between March 1999 and March 2006 were analyzed. Protocol testing for DSA via single antigen beads was done before transplantation and at 1, 3, 6, 9, and 12 months after transplantation then annually. Estimated glomerular filtration rate (eGFR) was analyzed before and after DSA onset. Forty-two patients developed DSA and had adequate eGFR information for analysis. Before DSA onset, the 42 patients had stable eGFR. By 1 year post-DSA, the cohort's eGFR was significantly lower (P<0.001); however, 30 of 42 had stable function. Twelve patients had failure or early allograft dysfunction (eGFR decline >25% from DSA onset). Those who failed early (by 1 year post-DSA) had more antibody-mediated rejection than stable patients (P=0.03). Late failures (after 1 year post-DSA) were predictable with evidence of early allograft dysfunction (eGFR decline >25% by 1 year post-DSA; P<0.001). Early allograft dysfunction preceded late failure by nearly 1 year. DSA is temporally related to allograft function deterioration. However, in many cases, late allograft failures are preceded by early allograft dysfunction. Therefore, monitoring for early allograft dysfunction provides treating physicians with a window of opportunity for treatment or continued monitoring.