Antithymocyte globulin is associated with a lower incidence of de novo donor-specific antibodies in moderately sensitized renal transplant recipients.

BACKGROUND: Recent evidence suggests that de novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and graft failure after kidney transplantation. The effects of induction immunosuppression on dnDSA are unknown. METHODS: The study population comprised 114 consecutive moderately sensitized (positive DSA and negative flow crossmatch) recipients who received deceased donor renal transplants between December 2009 and November 2011. Patients were divided into two groups based on induction immunosuppression: antithymocyte globulin (ATG) (n=85) or basiliximab (n=29) and were followed up for 36 months. RESULTS: Patients in the ATG group received a mean dose of 4.98 mg/kg ± 7.9 mg/kg, had a significantly higher PRA, and received more plasmapheresis and IVIG at the time of transplant. The incidence of dnDSA (P=0.02, HR=0.33, 95% CI 0.09-1.24) and ABMR (P=0.002, HR=0.2, 95% CI 0.04-0.87) was significantly lower in the ATG group. In multivariate regression analyses, ATG induction was the single most important variable associated with both ABMR and dnDSA. CONCLUSIONS: In moderately sensitized deceased donor renal transplant recipients, induction with ATG is associated with a reduction in the occurrence of dnDSA and ABMR when compared with basiliximab.

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.

In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

Differential outcomes of expanded-criteria donor renal allografts according to recipient age.

BACKGROUND AND OBJECTIVES: Expanded-criteria donor (ECD) kidneys are used to expand the number of deceased-donor kidney transplants, often for elderly recipients. This study sought to determine whether older recipients had significantly worse outcomes from receiving ECD kidneys and whether outcomes of ECD versus standard-criteria donor (SCD) kidneys differed in younger recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a single-center, retrospective review of all primary deceased-donor kidney transplantations performed between 2000 and 2005. Group 1 consisted of patients ≥60 years of age (n=189) who received an ECD (n=96) or an SCD (n=93) kidney. Group 2 consisted of patients 40-59 years of age (n=370) who received an ECD (n=105) or an SCD (n=265) kidney. RESULTS: Older recipients (group 1) who received ECD kidneys demonstrated significantly shortened 5-year actuarial patient and graft survival rates compared with older recipients of SCD allografts. Group 1 ECD recipients also had significantly worse outcomes than younger (group 2) ECD recipients. In multivariate analysis, ECD kidneys remained an independent predictor of poorer outcome in group 1. CONCLUSIONS: Morbidity and mortality were increased in elderly recipients of ECD kidneys. These findings may have implications in kidney allocation policy developments that encourage placement of ECD kidneys for older recipients.

Donation after cardiac death: a 29-year experience.

OBJECTIVE: To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008. METHODS: One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD). RESULTS: Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients. CONCLUSION: This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors.

Simultaneous liver and kidney transplantation using donation after cardiac death donors: a brief report.

Although the use of donation after cardiac death (DCD) donor organs has been shown to be a viable option for liver and kidney transplant recipients, outcomes after simultaneous liver and kidney (SLK) transplantation using DCD donors are less clear. We performed a retrospective analysis of 37 adult, primary SLK transplants performed at our center between January 1, 1998 and December 31, 2008. Thirty-two patients received donation after brain death (DBD) organs, and 5 patients received DCD organs. SLK recipients in the 2 groups were similar with respect to age, gender, race, body mass index, donor race, and donor body mass index. The calculated Model for End-Stage Liver Disease scores and pretransplant glomerular filtration rates were similar between the groups. DCD donors were younger and had shorter liver cold ischemia times. The median DCD donor warm ischemia time was 19.0 minutes (6.0-25.0 minutes). The recipient surgical times and hospital lengths of stay were comparable between the groups. Delayed graft function was more frequent in DCD renal allografts (80% versus 31%, P = 0.06). The 1-year graft survival rates for liver allografts (100% for the DCD group versus 94% for the DBD group) and kidney allografts (100% for the DCD group versus 94% for the DBD group) were similar. In conclusion, patients undergoing DCD SLK transplantation have comparable 1-year patient and graft survival rates and acceptable perioperative morbidity in comparison with DBD SLK transplant recipients. Although long-term outcomes remain unknown, the utilization of DCD organs for SLK transplantation should be considered a valid approach to safely expanding the donor organ pool.