Faculty Bibliography

There is an increase in the older incident end-stage renal disease population that is associated with an increasing prevalence of end-stage renal disease in the United States. This trend is paralleled by an increasing rate of kidney transplantation in the elderly. Although patient survival is lower in older versus younger kidney recipients, the elderly benefit from a reduction in mortality rate and improved quality of life with transplantation compared with dialysis. Immunologic, physiologic, and psychosocial factors influence transplant outcomes and should be recognized in the care of the elderly transplant patient. In this review, we discuss transplantation in the elderly patient, particularly the topics of access to transplantation, patient and graft survival, the impact of donor quality on transplant outcomes, immunology and immunosuppression of aging, and ethical considerations in the development of an equitable organ allocation scheme.

We report a chain of 10 kidney transplantations, initiated in July 2007 by a single altruistic donor (i.e., a donor without a designated recipient) and coordinated over a period of 8 months by two large paired-donation registries. These transplantations involved six transplantation centers in five states. In the case of five of the transplantations, the donors and their coregistered recipients underwent surgery simultaneously. In the other five cases, "bridge donors" continued the chain as many as 5 months after the coregistered recipients in their own pairs had received transplants. This report of a chain of paired kidney donations, in which the transplantations were not necessarily performed simultaneously, illustrates the potential of this strategy.

Women have less access to kidney transplantation than men, but the contributions of age and comorbidity to this disparity are largely unknown. We conducted a national cohort study of 563,197 patients with first-onset ESRD between 2000 and 2005. We used multivariate generalized linear models to evaluate both access to transplantation (ATT), defined as either registration for the deceased-donor waiting list or receiving a live-donor transplant, and survival benefit from transplantation, defined as the relative rate of survival after transplantation compared with the rate of survival on dialysis. We compared relative risks (RRs) between women and men, stratified by age categories and the presence of common comorbidities. Overall, women had 11% less ATT than men. When the model was stratified by age, 18- to 45-yr-old women had equivalent ATT to men (RR 1.01), but with increasing age, ATT for women declined dramatically, reaching a RR of 0.41 for those who were older than 75 yr, despite equivalent survival benefits from transplantation between men and women in all age subgroups. Furthermore, ATT for women with comorbidities was lower than that for men with the same comorbidities, again despite similar survival benefits from transplantation. This study suggests that there is no disparity in ATT for women in general but rather a marked disparity in ATT for older women and women with comorbidities. These disparities exist despite similar survival benefits from transplantation for men and women regardless of age or comorbidities.

In the highly active antiretroviral therapy era of improved survival for patients living with human immunodeficiency virus (HIV), chronic kidney disease now accounts for more than 10% of HIV-related deaths. The role of kidney transplant among HIV-positive patients with end-stage renal disease is under consideration, but concerns remain regarding allocation of kidneys to these patients when long-term benefit has not been firmly established. We evaluated 39,501 patients undergoing a renal transplant between January 1, 2004, and June 30, 2006, identified through the United Network for Organ Sharing national registry and found that, although long-term allograft survival is lower among HIV-positive recipients, controllable risk factors may explain this disparity. With proper donor selection and transplant recipient management, including the avoidance of prolonged cold ischemic time, use of living donors, and determination of optimal immunosuppression dosing before transplant, long-term graft survival comparable to that in HIV-negative patients can be achieved.

We present four cases of renal transplant recipients who were treated with bortezomib for four different indications, each of whom had circulating anti-HLA antibodies that were followed serially throughout their courses of bortezomib therapy. It is important to note that each patient was administered bortezomib in conjunction with other agents and therapies traditionally used for desensitization or the treatment of AMR. The results have been mixed. In some cases substantial decreases in HLA-antibody were temporally related to bortezomib therapy. In the one case of recalcitrant AMR there has been no reduction in DSA after 2 cycles of the drug. Bortezomib has been well tolerated. One patient developed reversible peripheral neuropathic pain while another experienced line sepsis, a urinary tract infection, and an invasive fungal skin infection. Again, this patient had also received protracted courses of plasmapheresis combined with T-cell and B-cell depleting agents. The use of these other drugs precludes the ability to rigorously evaluate the efficacy of bortezomib in isolation and points towards a need for large-scale, controlled trials to determine whether the drug's promising mechanism of action is applicable in the setting of solid organ transplantation.

BACKGROUND: Successful ABO-incompatible (ABOi) kidney transplantation of non-A2 renal allografts requires preconditioning to reduce anti-blood group antibody to safe lev-els in order to avoid hyperacute rejection. Unfortunately, early post-transplant acute antibody-mediated rejection remains a problem in these patients and can result in rapid graft loss. A number of investigators have encountered ABOi recipients who have had no evidence of allograft injury in the setting of elevated titers of anti-ABO antibody, a protective phenomenon that has been termed 'accommodation'. Little is known about the time course of accommodation. We report a case of a successful ABOi renal transplant recipient who had evidence of accommodation within the first week following transplantation. CASE REPORT: The patient is a 36-year-old, highly sensitized blood group.woman who underwent live donor transplantation from her human leukocyte antigen-identical blood group A1 brother following therapy with plasmapheresis and low-dose intravenous immunoglobulin for an initial anti-A anti-human globulin antibody titer of 512. Within the first week following transplantation, her anti-A titer rose to 128 without change in her renal function. At 1 month following transplantation, her anti-A titer had risen to 256 at which time a biopsy was per-formed that demonstrated no evidence of antibody-mediated rejection. CONCLUSION: This patient demonstrates that accommodation of the renal allograft following ABOi transplantation may take place in the early postoperative period in the setting of high titer antibody. The implications for postoperative management of the ABOi patient and the need for future investigation in this area are discussed.

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.

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.