Faculty Bibliography

Partial hepatectomy for hepatocellular carcinoma (HCC) is a high-risk procedure, especially in the presence of portal hypertension. We assessed whether the volume of hospital liver transplant procedures was associated with lower in-hospital mortality independently of the volume of partial hepatectomy procedures. We queried the Nationwide Inpatient Sample (1998-2005) to identify patients who had undergone partial hepatectomy for HCC and used logistic regression to assess the independent effect of volumes of hospital liver transplant and partial hepatectomy procedures on mortality while adjusting for demographic, clinical, and hospital factors. Overall in-hospital mortality was 7.7%. Patients with portal hypertension experienced higher mortality than those who did not (24.5% versus 5.8%, P < 0.0001). Postoperative mortality benefited from a higher volume of hospital liver transplants (>12 per year) and partial hepatectomy procedures (>5 resections per year). Undergoing partial hepatectomy at a center that performed an effective liver transplant volume (eLTV; >12 transplants per year) was associated with lower mortality in both the portal hypertensive group (16.4% versus 33.7%, P = 0.004) and non-portal hypertensive group (4% versus 8%, P = 0.0002). After multivariate adjustment, the odds ratio (OR) of in-hospital death for those with portal hypertension was 4.5 [95% confidence interval (CI), 2.98-6.81]. The lower mortality observed with eLTV (OR, 0.59; 95% CI, 0.37-0.93) was independent of the mortality benefit from an effective partial hepatectomy volume (>5 hepatectomies per year; OR, 0.54; 95% CI, 0.31-0.94). Postoperative complications were also fewer at centers with eLTV compared to those without eLTV (39.2% versus 29.3%, P < 0.0001). In conclusion, given the postoperative mortality benefit independent of the volume of partial hepatectomy procedures, referral to a center with eLTV should be considered for HCC resection, especially in the presence of portal hypertension.

The requirements for potent immunosuppression coupled with the formidable risk of irreversible antibody-mediated rejection (AMR) have thus far limited the expansion of ABO incompatible (ABOi) kidney transplantation. We present a retrospective review of our single-center experience with 60 consecutive ABOi kidney transplants and describe the evolution of our treatment protocol to one that consists only of a brief escalation in immunosuppression without long-term B-cell suppression from splenectomy or anti-CD20. The 1-, 3-, and 5-year graft survival rates for the cohort were 98.3%, 92.9%, and 88.7%, respectively, which is comparable with United Network for Organ Sharing data for compatible live donor transplants. No instances of hyperacute rejection were observed, and no grafts were lost secondary to AMR. In fact, fewer than 15% of the patients experienced a clinical episode of AMR, and rejections were mild. Elimination of B-cell ablative therapies did not result in an increased incidence of AMR. Excellent graft function persists with a current median creatinine clearance of 60 mL/min. The findings of this study and the relatively simple therapeutic regimen used should facilitate widespread application of ABOi kidney transplantation resulting in one of the most rapid escalations in access to organs in the modern era of kidney transplantation.

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.

C4d deposition in peritubular capillaries is a specific marker for the presence of antidonor antibodies in renal transplant recipients and is usually associated with antibody-mediated rejection (AMR) in conventional allografts. In ABO-incompatible grafts, however, peritubular capillary C4d is often present on protocol biopsies lacking histologic features of AMR; the significance of C4d in this setting remains unclear. For addressing this, data from 33 patients who received ABO-incompatible renal allografts (after desensitization) were retrospectively reviewed. Protocol biopsies were performed at 1 and/or 3 and 6 mo after transplantation in each recipient and at 12 mo in 28 recipients. Twenty-one patients (group A) had strong, diffuse peritubular capillary C4d staining without histologic evidence of AMR or cellular rejection on their initial protocol biopsies. The remaining 12 patients (group B) had negative or weak, focal peritubular capillary C4d staining. Three grafts (two in group B) were lost but not as a result of AMR. Excluding these three patients, serum creatinine levels were similar in the two groups at 6 and 12 mo after transplantation and at last follow-up; however, recipients in group A developed significantly fewer overall chronic changes, as scored by the sum of Banff chronic indices, than group B during the first year after transplantation. These results suggest that diffuse peritubular capillary C4d deposition without rejection is associated with a lower risk for scarring in ABO-incompatible renal allografts; the generalizability of these results to conventional allografts remains unknown.

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.