Belatacept Conversion Protocols and Outcomes in Kidney Transplant Recipients.

BACKGROUND: Conversion from calcineurin inhibitor (CNI)-based to belatacept-based immunosuppression has become common; however, numerous protocols have emerged in lieu of a standardized protocol. The purpose of this study was to characterize belatacept conversion protocols from multiple centers and observe outcomes. METHODS: This was a retrospective study that included Kaiser Permanente Southern California members. The primary outcome was rejection 6 months after conversion and secondary outcomes included change in serum creatinine and graft loss. RESULTS: Seventy-eight patients were included. Thirteen distinct protocols were identified from 8 different transplant centers. Protocols varied by initial dose, induction schedule, and CNI taper. The observed rate of rejection was 6%. There was a trend toward an association of rejection with lower tacrolimus exposure at the time of conversion and lower mycophenolic acid dosing postconversion. Graft survival was 88% and patient survival was 94%. There was a significant improvement in creatinine after conversion. Those with early conversions and creatinine >2.0 mg/dL at the time of conversion had the best response. CONCLUSIONS: A large variety of belatacept conversion protocols were identified. Protocols were defined by the initial dose, induction regimen, and CNI taper. Rejection rates were low and may be influenced by exposure to maintenance immunosuppression during and after conversion. Most patients showed stabilization and improvement in creatinine postconversion, with the largest effect in those with an early conversion and serum creatinine >2.0 mg/dL.

Differences in pathologic features and graft outcomes in antibody-mediated rejection of renal allografts due to persistent/recurrent versus de novo donor-specific antibodies.

Antibody-mediated rejection (ABMR) of renal allografts occurs in two forms. Type 1 ABMR results from persistence and/or a rebound of preexisting donor-specific antibodies in sensitized patients and usually occurs early post-transplantation. Type 2 ABMR is associated with de novo donor-specific antibodies and usually occurs over one year post-transplantation. It is generally accepted that types 1 and 2 also differ with regard to certain pathologic features including the frequencies of C4d positivity and concurrent cell-mediated rejection. However, direct comparison of pathologic, serologic, and clinical features of types 1 and 2 ABMR is lacking. Here we compared these features in 80 cases of ABMR (37 type 1, 43 type 2) diagnosed at our center. Compared with type 1, type 2 ABMR occurred later post-transplantation, was more often associated with donor-specific antibodies against Class II HLA, and was associated with more interstitial fibrosis/tubular atrophy and more frequent cell-mediated rejection, although these did not differ with respect to C4d positivity. By univariate analysis, graft survival was lower with type 2 than type 1 ABMR with borderline significance. Still, among these 80 patients, all but one treated for ABMR following diagnosis, the only two independent predictors of graft failure were at least moderate interstitial fibrosis/tubular atrophy and failure of the donor-specific antibody relative intensity scale score, a measure of the combined strength of all donor-specific antibodies present, to decrease in response to therapy.