The development of de novo donor-specific antibody (dnDSA) is an independent predictor of allograft loss in renal transplantation. Rates and determinants of clinical pathologic progression for recipients who develop dnDSA, especially subclinical dnDSA, are required to evaluate the effectiveness of current or novel therapies. A consecutive cohort of 560 renal transplant recipients (n=63 with dnDSA) was studied using clinical, serologic, and pathologic data. Recipients that developed dnDSA had a 3-fold increase in the rate of eGFR decline (0.36 vs. 1.07 ml/min/year, p<0.0001). Graft dysfunction at dnDSA onset was associated with a step-wise decline in eGFR of 16.5±3.0 ml/min (p<0.0001) after which subclinical and clinical dnDSA had similar rates of eGFR decline (1.32 vs 0.96 ml/min/year, p=0.446). Histologic analysis of 1,088 biopsies pre and post-dnDSA development found that dnDSA independently predicted chronic glomerulopathy, but not interstitial fibrosis and tubular atrophy (IFTA), or chronic vasculopathy. Non-adherence, early cellular rejection, and time were independent predictors of IFTA. Predictors of post-dnDSA graft survival available at dnDSA detection were clinical dysfunction, dnDSA mean fluorescence intensity sum score, tubulointerstitial inflammation, and chronic glomerulopathy. Understanding the risk factors of eGFR decline and post-dnDSA detection graft loss could help design and select recipients for therapeutic trials.

« Back to 2015 American Transplant Congress