The clinical importance of flow cytometry crossmatch in the context of CDC crossmatch results.

BACKGROUND: The complement-dependent microcytotoxicity crossmatch (CDCXM) is a standard method for evaluating the presence of preformed antibodies before transplantation. The flow cytometry crossmatch (FCXM) is more sensitive, but there is controversy regarding translation of its increased sensitivity to clinically relevant graft outcomes. METHODS: We analyzed Organ Procurement and Transplant Network registry data for living and deceased donor kidney transplants performed in 1995 to 2009 after both CDCXM and FCXM testing. Transplants with negative CDCXM (CDCXM(-)) and with T-cell positive (T(+)), T-cell negative/B-cell positive (T(-)B(+)), or T- and B-cell negative (T(-)B(-)) FCXM results were included. Graft survival according to crossmatch results was compared by survival analysis. RESULTS: Among patients transplanted with negative CDCXM (CDCXM(-)), deceased and living donor graft recipients with T(+) FXCM experienced significant absolute reductions in 5-year graft survival of 11.5% and 8.8% compared to those with T(-) FCXM (P < .0001). Compared to patients with FCXM(-)/CDCXM(-) deceased and living donor recipients with T(-)B(+) FCXM/CDCXM(-) had absolute reductions in 5-year graft survival of 9.6% and 7.6%, respectively (P < .0001). Upon multivariate adjustment with Cox regression, T(+) FCXM/CDCXM(-) deceased donor transplantation was associated with 51% higher adjusted relative risk of 1-year graft loss than FCXM(-)/CDCXM(-). Relative risks were more marked at 1 year for the T(+) groups but stronger in the 1- to 5-year interval for the T(-)B(+) groups. CONCLUSION: Positive FCXM has important prognostic implications even when CDCXM is negative. Thus, positive FCXM should not routinely be dismissed as "overly sensitive" when CDCXM is negative.

Predictive ability of pretransplant comorbidities to predict long-term graft loss and death.

Whether to include additional comorbidities beyond diabetes in future kidney allocation schemes is controversial. We investigated the predictive ability of multiple pretransplant comorbidities for graft and patient survival. We included first-kidney transplant deceased donor recipients if Medicare was the primary payer for at least one year pretransplant. We extracted pretransplant comorbidities from Medicare claims with the Clinical Classifications Software (CCS), Charlson and Elixhauser comorbidities and used Cox regressions for graft loss, death with function (DWF) and death. Four models were compared: (1) Organ Procurement Transplant Network (OPTN) recipient and donor factors, (2) OPTN + CCS, (3) OPTN + Charlson and (4) OPTN + Elixhauser. Patients were censored at 9 years or loss to follow-up. Predictive performance was evaluated with the c-statistic. We examined 25 270 transplants between 1995 and 2002. For graft loss, the predictive value of all models was statistically and practically similar (Model 1: 0.61 [0.60 0.62], Model 2: 0.63 [0.62 0.64], Models 3 and 4: 0.62 [0.61 0.63]). For DWF and death, performance improved to 0.70 and was slightly better with the CCS. Pretransplant comorbidities derived from administrative claims did not identify factors not collected on OPTN that had a significant impact on graft outcome predictions. This has important implications for the revisions to the kidney allocation scheme.

Association of lower costs of pulsatile machine perfusion in renal transplantation from expanded criteria donors.

Pulsatile machine perfusion (PMP) has been shown to reduce delayed graft function (DGF) in expanded criteria donor (ECD) kidneys. Here, we investigate whether there is a cost benefit associated with PMP utilization in ECD kidney transplants. We analyzed United States Renal Data System (USRDS) data describing Medicare-insured ECD kidney transplant recipients in 1995-2004 (N = 5840). We examined total Medicare payments for transplant hospitalization and annually for 3 years posttransplant according to PMP utilization. After adjusting for other recipient, donor and transplant factors, PMP utilization was associated with a $2130 reduction (p = 0.007) in hospitalization costs. PMP utilization was also associated with lower DGF risk (p < 0.0001). PMP utilization did not predict differences in rejection, graft survival, patient survival, or costs at 1, 2 and 3 years posttransplant. PMP utilization is correlated with lower costs for the transplant hospitalization, which is likely due to the associated reduction in DGF among recipients of PMP kidneys. However, there is no difference in long-term Medicare costs for ECD recipients by PMP utilization. A prospective trial is necessary as it will help determine if the associations seen here are due to PMP utilization and not differences in the population studied.

Monozygotic transplantation: concerns and opportunities.

We describe the case of a 24-year-old female with end-stage renal disease from focal segmental glomerulosclerosis (FSGS) diagnosed at age 16, who underwent monozygotic triplet transplantation at age 21 from her sister. Monozygosity was established by buccal smear DNA PCR amplification using short tandem repeat (1) profiling for 16 genetic alleles. All immunosuppression was discontinued by 1 month posttransplant. To evaluate the use of immunosuppression in HLA identical monozygotic transplantation, we interrogated the OPTN (Organ Procurement Transplant Network) database for all transplants conducted from 1987 to 2006. We identified 194 probable identical twin transplantations based on age, gender, race, ethnic category, blood type and HLA match. We evaluated the use of various immunosuppressive agents at discharge, 6 months and 1, 2 and 3 years after transplantation. Seventy-one percent of these patients at discharge and 34% at the end of 1 year were on immunosuppression. At discharge 61% received steroids and 30% received calcineurin inhibitors and 66% of these remained on calcineurin inhibitors at 1 year. Renal function was superior among those not maintained on immunosuppression. Thus, monozygotic transplantation confers an immunologic advantage that allows immunosuppression elimination despite a risk of recurrent glomerular disease such as FSGS with appropriate evaluation and management.