Persistence of De Novo Donor Specific Antibodies Results in Higher Rates of Acute Rejection and Graft Loss in Renal Transplant Recipients With Stable Renal Function.

Abstract

Background: Most studies have focused on single time point detection of de novo donor specific antibodies (dnDSA) and on adverse outcomes after renal transplant. Longitudinal studies of sensitized dialysis patients have reported that some patients spontaneously clear antibodies, but the pattern and impact of antibody clearance is unknown. We sought to determine the rate of spontaneous clearance of dnDSA after renal transplant and to describe the outcomes associated with dnDSA clearance versus dnDSA persistence in patients without prior rejection. Methods: We prospectively monitored 828 kidney transplants for dnDSA from 7/2007 - 7/2012. All had at least 1 year follow-up. We excluded 120 patients with graft failure or death < 1 month post-transplant, DSA prior to transplant, acute rejection (AR) prior to dnDSA, or treatment of dnDSA with IVIG. Recipients with a single positive dnDSA followed by no additional positive tests were considered isolated (IsoDSA) and those with at least 2 positive tests were persistent (PersDSA). Results: One-hundred fifty-seven of 708 (22%) patients with stable renal function and no prior AR developed a dnDSA. Of these, 36% were IsoDSA and 64% were PersDSA. IsoDSA occurred later than persDSA (6.3 (IQR 1.1-12.7 months) vs. 3.2 (IQR 0.9-11.8 months) respectively; p<0.05). AR occurred more often in PersDSA patients than in IsoDSA patients (1.8% vs. 22% respectively; p<0.001) (Figure 1a). Moreover, recipients with persDSA had more graft loss compared to IsoDSA (0 vs. 10.5% respectively; p=0.014) (Figure 1b).Figure: No Caption available.Figure: No Caption available.Conclusions: In a large cohort of prospectively monitored renal transplant recipients without acute rejection prior to dnDSA, 22% develop dnDSA, 64% of which remained as PersDSA and 36% of which spontaneously resolved (IsoDSA). There was a higher rate of rejection and graft loss in recipients with PersDSA, and dnDSA developed earlier in recipients with PersDSA compared to recipients with IsoDSA. Recipients with 2 dnDSA (PersDSA) warrant increased monitoring and could be more likely candidates for preemptive treatment.