Faculty Bibliography

In the setting of disparities in access to simultaneous pancreas and kidney transplantation (SPKT), Medicare coverage for this procedure was initiated July 1999. The impact of this change has not yet been studied. A national cohort of 22 190 type 1 diabetic candidates aged 18-55 for kidney transplantation (KT) alone or SPKT was analyzed. Before Medicare coverage, 57% of Caucasian, 36% of African American and 38% of Hispanic type 1 diabetics were registered for SPKT versus KT alone. After Medicare coverage, these proportions increased to 68%, 45% and 43%, respectively. The overall increase in SPKT registration rate was 27% (95% CI 1.16-1.38). As expected, the increase was more substantial in patients with Medicare primary insurance than those with private insurance (Relative Rate 1.18, 95% CI 1.09-1.28). However, racial disparities were unaffected by this policy change (African American vs. Caucasian: 0.97, 95% CI 0.87-1.09; Hispanic vs. Caucasian: 0.94, 95% CI 0.78-1.05). Even after Medicare coverage, African Americans and Hispanics had almost 30% lower SPKT registration rates than their Caucasian counterparts (95% CI 0.66-0.79 and 0.59-0.80, respectively). Medicare coverage for SPKT succeeded in increasing access for patients with Medicare, but did not affect the substantial racial disparities in access to this procedure.

Hepatic artery thrombosis (HAT) is the most common vascular complication after liver transplantation; it has been reported to occur in 2% to 5% of liver transplant recipients. Most reports of HAT in the literature describe single-center series with small numbers of patients and lack the power to definitively identify nontechnical risk factors. We used the United Network for Organ Sharing database of adult deceased donor liver transplants from 1987 to 2006 to identify 1246 patients with graft loss from HAT. Univariate and multivariate regression analyses were performed to identify donor and graft risk factors for HAT-induced graft loss. Although most donor predictors of HAT-induced graft loss were surrogates for vessel size, donor age > 50 years was also a significant predictor of graft loss from HAT (relative risk = 1.45, P < 0.001). Furthermore, the risk of graft loss from HAT increased progressively with each decade of donor age > 50 years, such that a 61% increased risk of HAT-related graft loss (relative risk = 1.61, P < 0.001) was associated with donor age > 70 years. A separate analysis of risk factors for early HAT graft loss ( 90 days) found that older donor age was associated with increased late HAT graft loss. These findings are of interest in an era of ongoing organ shortages requiring maximum utilization of potential allografts and increasing allocation of older allografts.

Identification of factors responsible for an increase in the breadth or strength of HLA-specific antibody (HSA) is critical to the continued successful management and transplantation of sensitized patients. A retrospective review of our HLA registry identified 107 patients with known HSA and sufficient information in their electronic patient record to determine the presence or absence of a proinflammatory event. The patients were stratified according to transplant status [sensitized and on the transplant waitlist (n = 65); immunosuppressed recipients of a positive crossmatch (+XM) transplant (n = 42)]. Eighty-three percent of waitlist candidates and 55% of sensitized kidney transplant recipients with a documented proinflammatory event had an associated increase in HSA. Interestingly, among patients with a culture-proven infection, 97% of the waitlist patients and 54.8% of +XM recipients had an associated rise in HSA. Overall, proinflammatory events were associated with a greater increase among waitlist patients than +XM recipients, 5.3-fold [IRR 5.25, (95% CI 4.03-6.85), p < 0.001] versus 2.5-fold [IRR 2.54, (95% CI 1.64-3.95), p < 0.001] increase in HSA. Therefore, sensitized patients known to have an infection or undergoing surgery should be monitored for expansion of HSA.

We reviewed 116 surveillance biopsies obtained approximately 1, 3, 6 and 12 months posttransplantation from 50 +XM live donor kidney transplant recipients to determine the frequency of subclinical cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). Subclinical CMR was present in 39.7% of the biopsies at 1 month and >20% at all other time points. The presence of diffuse C4d on biopsies obtained at each time interval ranged from 20 to 30%. In every case, where histological and immunohistological findings were diagnostic for AMR, donor-specific antibody was found in the blood, challenging the long-held belief that low-level antibody could evade detection due to absorption on the graft. Among clinical factors, only recipient age was associated with subclinical CMR. Clinical factors associated with subclinical AMR were recipient age, positive cytotoxic crossmatch prior to desensitization and two mismatches of HLA DR 51, 52 and 53 alleles. Surveillance biopsies during the first year post-transplantation for these high-risk patients uncover clinically occult processes and phenotypes, which without intervention diminish allograft survival and function.

In the United States, ABO-incompatible liver transplantation (ILT) is limited to emergent situations when ABO-compatible liver transplantation (CLT) is unavailable. We analyzed the United Network for Organ Sharing database of ILT performed from 1990-2006 to assess ILT outcomes for infant (0-1 years; N = 156), pediatric (2-17 years; N = 170), and adult (> 17 years; N = 667) patients. Since 2000, the number of ILT has decreased annually, and there has been decreased use of blood type B donors and increased use of blood type A donors. Furthermore, ILT graft survival has improved for all age groups in recent years, beyond the improved graft survival attributable to era effect based on comparison to respective age group CLT. On matched control analysis, graft survival was significantly worse for adult ILT as compared to adult CLT. However, infant and pediatric ILTs did not have worse graft survival versus age-matched CLT. Adjusted analyses identified age-specific characteristics impacting ILT graft loss. For infants, transplant after 2000 and donor age < 9 years were associated with reduced risk of ILT graft loss. For pediatric patients, female recipient sex and donor age > 50 years were associated with increased risk of ILT graft loss. For adults, life support, repeat transplant, split grafts, and hepatocellular carcinoma were associated with increased risk of ILT graft loss. The current study identifies important trends in ILT in the United States in the modern immunosuppression era, as well as specific recipient, donor, and graft characteristics impacting ILT graft survival that could be utilized to guide ILT organ allocation in exigent circumstances. Liver Transpl 15:883-893, 2009. (c) 2009 AASLD.

In 2007, UNOS released DonorNet 2007 (DN07) in hope of improving allocation equity and efficiency. We hypothesized that hard-to-place organs might be less efficiently handled through this regimented process. We analyzed associations between DN07 and center-level equity, number of refusals per organ and cold ischemia time (CIT). A total of 8244 kidney transplants between 1/2006 and 12/2006 (pre-DN07) were compared with 6029 transplants between 5/2007 and 2/2008 (post-DN07). Distribution equity was assessed by the Gini coefficient, changes in the number of refusals and CIT by negative binomial regression and discard rates by logistic regression. We estimated quantile-specific differences in CIT by bootstrapping. We found no significant change in center-level distribution equity after DN07. Number of refusals per organ increased by 20% (adjusted rate ratio (1.12)1.20(1.28), p < 0.001) at the patient level and 11% (ARR (1.07)1.11(1.16), p < 0.001) at the center level. Regression models of CIT showed no global change in CIT associated with DN07, but those kidneys with the longest CIT pre-DN07 had statistically significantly longer CIT post-DN07. The discard rate also increased significantly (ARR (1.06)1.11(1.17), p < 0.001). DN07 has not improved equity or efficiency in allocation of deceased donor kidneys, and may be harming the allocation of hard-to-place kidneys.