Evolution and Clinical Pathologic Correlations of De Novo Donor-Specific HLA Antibody Post Kidney Transplant

TLDR

The natural history and risk factors for de novo donor‑specific HLA antibodies after kidney transplant remain poorly defined, and clinical–histologic correlations are limited. We followed 315 kidney transplant recipients without pre‑transplant DSA for a mean of 6.2 years, performing protocol and for‑cause biopsies and screening for dnDSA with solid‑phase assays. Fifteen percent of patients developed dnDSA at a mean of 4.6 years, with HLA‑DRβ1 MM > 0 and nonadherence as independent predictors, and dnDSA was associated with lower 10‑year graft survival (57 % vs 96 %) and antibody‑mediated injury that can progress even without graft dysfunction.

Abstract

The natural history for patients with de novo donor-specific antibodies (dnDSA) and the risk factors for its development have not been well defined. Furthermore, clinical and histologic correlation with serologic data is limited. We studied 315 consecutive renal transplants without pretransplant DSA, with a mean follow-up of 6.2 ± 2.9 years. Protocol (n = 215) and for cause (n = 163) biopsies were analyzed. Solid phase assays were used to screen for dnDSA posttransplant. A total of 47 out of 315 (15%) patients developed dnDSA at a mean of 4.6 ± 3.0 years posttransplant. Independent predictors of dnDSA were HLA-DRβ1 MM > 0 (OR 5.66, p < 0.006); and nonadherence (OR 8.75, p < 0.001); with a strong trend toward clinical rejection episodes preceding dnDSA (OR 1.57 per rejection episode, p = 0.061). The median 10-year graft survival for those with dnDSA was lower than the No dnDSA group (57% vs. 96%, p < 0.0001). Pathology consistent with antibody-mediated injury can occur and progress in patients with dnDSA in the absence of graft dysfunction and furthermore, nonadherence and cellular rejection contribute to dnDSA development and progression to graft loss.