Faculty Bibliography

A 43-year-old patient with end-stage renal disease, a hypercoagulable condition and 100% panel reactive antibody was transferred to our institution with loss of hemodialysis access and thrombosis of the superior and inferior vena cava, bilateral iliac and femoral veins. A transhepatic catheter was placed but became infected. Access through a stented subclavian into a dilated azygos vein was established. Desensitization with two cycles of bortezomib was undertaken after anti-CD20 and IVIg were given. A flow-positive, cytotoxic-negative cross-match live-donor kidney at the end of an eight-way multi-institution domino chain became available, with a favorable genotype for this patient with impending total loss of a dialysis option. The patient received three pretransplant plasmapheresis treatments. Intraoperatively, the superior mesenteric vein was the only identifiable patent target for venous drainage. Eculizumab was administered postoperatively in the setting of antibody-mediated rejection and an inability to perform additional plasmapheresis. Creatinine remains normal at 6 months posttransplant and flow cross-match is negative. In this report, we describe the combined use of new agents (bortezomib and eculizumab) and modalities (nontraditional vascular access, splanchnic drainage of graft and domino paired donation) in a patient who would have died without transplantation.

We recently showed that DonorNet 2007 has reduced the efficiency of kidney distribution in the United States, particularly for those with prolonged cold ischemia time (CIT), by requiring systematic allocation of all kidneys regardless of quality. Reliable early identification of those most likely to be discarded or significantly delayed would enable assigning them to alternate, more efficient distribution strategies. Based on 39 035 adult kidneys recovered for possible transplantation between 2005 and 2008, we created a regression model that reliably (AUC 0.83) quantified the probability that a given kidney was either discarded or delayed beyond 36 h of CIT (Probability of Discard/Delay, PODD). We then analyzed two PODD cutoffs: a permissive cutoff that successfully flagged over half of those kidneys that were discarded/delayed, while only flagging 7% of kidneys that were not eventually discarded/delayed, and a more stringent cutoff that erroneously flagged only 3% but also correctly identified only 34%. Kidney transplants with high PODD were clustered in a minority of centers. Modifications of the kidney distribution system to more efficiently direct organs with high PODD to the centers that actually use them may result in reduced CIT and fewer discards.

Human leukocyte antigen (HLA) sensitization and ABO incompatibility continue to pose significant barriers to further expansion of live donor renal transplantation. However, the recent development of effective desensitization protocols and creative paired donation strategies demonstrates that the presence of circulating donor HLA-specific antibodies and the use of ABO incompatible organs should no longer be considered contraindications for renal transplantation. It is estimated that as many as 6,000 patients on the kidney transplant waiting list have incompatible living donors and could benefit from these treatments. Furthermore, as our understanding of these treatment modalities has improved, it is now possible to predict whether desensitization, kidney paired donation or a combination of both will provide an individual patient with their best chance for successful renal transplantation.

The recent decrease in the total number of living kidney transplants coupled with the increase in the number of candidates on the waiting list underscores the importance of eliminating barriers to living kidney donation. We report what we believe to be the first pure right-sided laparoscopic live donor nephrectomy with extraction of the kidney through the vagina. The warm ischemia time was 3 min and the renal vessels and ureter of the procured kidney were of adequate length for routine transplantation. The donor did not receive any postoperative parenteral narcotic analgesia, was discharged home within 24 h and was back to normal activity in 14 days. The kidney functioned well with no complications or infections. Laparoscopic live donor nephrectomy with vaginal extraction may be a viable alternative to open and standard laparoscopic approaches. Potential advantages include reduced postoperative pain, shorter hospital stay and convalescence and a more desirable cosmetic result. These possible, but yet unproven, advantages may encourage more individuals to consider live donation.

Therapeutic plasma exchange (TPE) preconditioning with immunosuppressive therapy reduces ABO antibody titers, permitting engraftment of ABO-incompatible (ABO-I) kidney transplants. The posttransplant predictive role of ABO antibody titers for antibody-mediated rejection (AMR) is unknown. This retrospective study evaluated 46 individuals who received TPE to permit ABO-I kidney transplantation. ABO antibody titers were performed using donor-type indicator red cells. Seven individuals (15.2%) experienced clinical or subclinical AMR. There was no significant difference between recipient blood group, number of pretransplant TPE and baseline titer between those with and without AMR. At 1-2 weeks posttransplant the median titer was 64 (range 4 - 512) among individuals with AMR and 16 (range 2 - 256) among individuals without AMR. Total agglutination reactivity score was significantly higher among individuals with AMR (p = 0.046). The risk of AMR was significantly higher among individuals with an elevated posttransplant titer of >or=64 (p = 0.006). The sensitivity of an elevated posttransplant titer was 57.1% with a specificity of 79.5%. The positive predictive value was 33.3% and the negative predictive value was 91.2%. Most individuals with AMR have an elevated titer, however, the positive predictive value of a high titer for AMR is poor.

Hepatitis C-positive (HCV(+)) candidates likely derive survival benefit from transplantation with HCV(+) kidneys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data has led to wide practice variation. Our goal was to characterize national utilization of HCV(+) kidneys for HCV(+) recipients, and to quantify the risks/benefits of this practice. Of 93,825 deceased donors between 1995 and 2009, HCV(+) kidneys were 2.60-times more likely to be discarded (p < 0.001). However, of 6830 HCV(+) recipients, only 29% received HCV(+) kidneys. Patients over 60 relative rate (RR 0.86), women (RR 0.73) and highly sensitized patients (RR 0.42) were less likely to receive HCV(+) kidneys, while African Americans (RR 1.56), diabetics (RR 1.29) and those at centers with long waiting times (RR 1.19) were more likely to receive them. HCV(+) recipients of HCV(+) kidneys waited 310 days less than the average waiting time at their center, and 395 days less than their counterparts at the same center who waited for HCV(-) kidneys, likely offsetting the slightly higher patient (HR 1.29) and graft loss (HR 1.18) associated with HCV(+) kidneys. A better understanding of the risks and benefits of transplanting HCV(+) recipients with HCV(+) kidneys will hopefully improve utilization of these kidneys in an evidence-based manner.

Certain patient groups are predicted to derive significant survival benefit from transplantation with expanded criteria donor (ECD) kidneys. An algorithm published in 2005 by Merion and colleagues characterizes this group: older adults, diabetics and registrants at centers with long waiting times. Our goal was to evaluate ECD listing practice patterns in the United States in terms of these characteristics. We reviewed 142 907 first-time deceased donor kidney registrants reported to United Network for Organ Sharing (UNOS) between 2003 and 2008. Of registrants predicted to benefit from ECD transplantation according to the Merion algorithm ('ECD-benefit'), 49.8% were listed for ECD offers ('ECD-willing'), with proportions ranging from 0% to 100% by transplant center. In contrast, 67.6% of adults over the age of 65 years were ECD-willing, also ranging from 0% to 100% by center. In multivariate models, neither diabetes nor center waiting time was significantly associated with ECD-willingness in any subgroup. From the time of initial registration, irrespective of eventual transplantation, ECD-willingness was associated with a significant adjusted survival advantage in the ECD-benefit group (HR for death 0.88, p < 0.001) and in older adults (HR 0.89, p < 0.001), but an increased mortality in non-ECD-benefit registrants (HR 1.11, p < 0.001). In conclusion, ECD listing practices are widely varied and not consistent with published recommendations, a pattern that may disenfranchise certain transplant registrants.