Faculty Bibliography

BACKGROUND:Antibody-mediated rejection (AMR) is a major barrier to the long-term function of renal allografts. White blood cells, which may be present in red blood cell (RBC) units, and platelets (PLTs) express HLA antigens that may increase the risk of AMR by inducing or increasing humoral sensitization to HLA. STUDY DESIGN AND METHODS/METHODS:A retrospective cohort study of HLA-incompatible (HLAi) renal transplant recipients between 2004 and 2015 was conducted. Data on apheresis PLT and leukoreduced RBC transfusions within 4 weeks of transplantation, demographic information, and biopsy-proven AMR were collected from medical records and the Scientific Registry of Transplant Recipients. Patients were evaluated until they showed evidence of AMR or until 1 year posttransplant, whichever came first. Multivariable analysis with Cox modeling was performed. RESULTS:Of 244 individuals, 182 (74.6%) received RBCs and 20 (8.2%) of those also received PLTs. During the first year posttransplant, 97 (39.8%) had AMR. RBC-alone or RBC and PLT transfusions were not associated with increased risk of AMR after adjustment for panel-reactive antibody, years on dialysis, HLA antibody strength, and number of therapeutic plasma exchange treatments (adjusted hazard ratio [adjHR] 1.00, 95% confidence interval [95% CI] 0.59-1.69; and adjHR 0.68, 95% CI 0.28-1.68, respectively). For each 1-unit increase in RBC transfusions, there was no association with AMR (adjHR 0.94, 95% CI 0.85-1.05). Only HLA antibody strength before transplantation was associated with AMR (adjHR 2.23, 95% CI 1.10-4.52; cytotoxic crossmatch compared to crossmatch negative but detectable donor-specific HLA antibodies). CONCLUSIONS:Patients who receive an HLAi transplant who are transfused with leukoreduced RBCs or PLTs in the peritransplant period are at no higher risk of AMR than nontransfused patients.

Kidney transplant recipients (KTR) have greater morbidity and length of stay (LOS) following certain surgical procedures than non-KTR. Given that appendectomy is one of the most common surgical procedures, we investigated differences in outcomes between 1336 KTR and 2,640,247 non-KTR post-appendectomy at transplant and non-transplant centers in the US from 2000-2011, using NIS data and adjusting for patient and hospital level factors. Postoperative complications were identified using ICD9 codes. Among KTR, there were no post-appendectomy in-hospital deaths, compared to a 0.2% in non-KTR (p=0.5). Overall complications were similar among KTR and non-KTR (17.0% vs 11.6%; aOR:_0.771.12_1.61). LOS and costs were greater for KTR compared to non-KTR (LOS ratio_1.191.31_1.45; cost ratio_1.111.17_1.26). Only 44.8% of KTR had laparoscopic approach compared to 54.5% of non-KTR, but had similar complication rates (10.6 vs 8.7%, p 0.5). When treated at transplant centers, KTR had similar complications (aOR_0.440.79_1.43), but longer LOS (ratio_1.211.37_1.55) and greater hospital-associated costs (ratio_1.191.29_1.41) than non-KTR. Conversely, at non-transplant centers, KTR and non-KTR had similar complications (aOR_0.751.23_2.0), LOS (ratio_0.840.96_1.09), and cost (ratio_0.931.01_1.10). Contrary to other procedures, KTR did not constitute a high-risk group for patients undergoing appendectomy.

BACKGROUND:Renal failure is common among patients undergoing liver transplantation. Liver allocation based on the model for end-stage liver disease score has increased the number of recipients who require perioperative renal replacement therapy (RRT). Although RRT can be continued intraoperatively, the risks and benefits of intraoperative RRT are not well defined. The aim of this study is to report the intraoperative management of patients with pretransplant renal failure at a transplant center with extremely infrequent utilization of intraoperative RRT. MATERIALS AND METHODS:We performed a retrospective analysis of all adult patients undergoing orthotopic liver or simultaneous liver-kidney (SLK) transplantation between June 2009 and December 2015. Patients were divided into 2 groups based on their need for pretransplant RRT. RESULTS:A total of 785 patients underwent liver or SLK transplant during the study period. One hundred and seventy-four patients (22.2%) required preoperative dialysis. Only 2 patients required intraoperative RRT. There was no difference in the incidence of acidosis or hyperkalemia between patients who required preoperative dialysis and those who did not. CONCLUSIONS:We describe the successful management of patients undergoing liver or SLK transplantation almost entirely without the need for intraoperative RRT.

30% of kidney transplant recipients are readmitted in the first month post-transplant. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95%CI: 1.13-1.46; P<0.001). Risk peaked at 6-12 months (RR 1.67; 95%CI: 1.49-1.87; P<0.001), attenuating by 24-36 months (RR 1.24; 95%CI: 1.10-1.40; P<0.001). ILDKTs had a 5.86-fold higher readmission risk (95%CI: 4.96-6.92; P<0.001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85; 95%CI: 0.77-0.95; P=0.002) and 24-36 months (RR 0.74; 95% CI: 0.66-0.84; P<0.001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.

Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNgamma response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.