Faculty Bibliography

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.

CONTEXT: More than 6000 healthy US individuals every year undergo nephrectomy for the purposes of live donation; however, safety remains in question because longitudinal outcome studies have occurred at single centers with limited generalizability. OBJECTIVES: To study national trends in live kidney donor selection and outcome, to estimate short-term operative risk in various strata of live donors, and to compare long-term death rates with a matched cohort of nondonors who are as similar to the donor cohort as possible and as free as possible from contraindications to live donation. DESIGN, SETTING, AND PARTICIPANTS: Live donors were drawn from a mandated national registry of 80 347 live kidney donors in the United States between April 1, 1994, and March 31, 2009. Median (interquartile range) follow-up was 6.3 (3.2-9.8) years. A matched cohort was drawn from 9364 participants of the third National Health and Nutrition Examination Survey (NHANES III) after excluding those with contraindications to kidney donation. MAIN OUTCOME MEASURES: Surgical mortality and long-term survival. RESULTS: There were 25 deaths within 90 days of live kidney donation during the study period. Surgical mortality from live kidney donation was 3.1 per 10,000 donors (95% confidence interval [CI], 2.0-4.6) and did not change during the last 15 years despite differences in practice and selection. Surgical mortality was higher in men than in women (5.1 vs 1.7 per 10,000 donors; risk ratio [RR], 3.0; 95% CI, 1.3-6.9; P = .007), in black vs white and Hispanic individuals (7.6 vs 2.6 and 2.0 per 10,000 donors; RR, 3.1; 95% CI, 1.3-7.1; P = .01), and in donors with hypertension vs without hypertension (36.7 vs 1.3 per 10,000 donors; RR, 27.4; 95% CI, 5.0-149.5; P < .001). However, long-term risk of death was no higher for live donors than for age- and comorbidity-matched NHANES III participants for all patients and also stratified by age, sex, and race. CONCLUSION: Among a cohort of live kidney donors compared with a healthy matched cohort, the mortality rate was not significantly increased after a median of 6.3 years.

The field of desensitization and incompatible transplantation has made great gains over the past decade. There are now several options and effective therapies for many patients who face antibody barriers. Kidney paired donation (KPD) and desensitization have traditionally been considered competing strategies and patients have been offered one or the other without regard for the probability of a successful outcome. It is now possible to predict which donor/recipient phenotypes will benefit from each of these modalities. KPD should be favored among patients with immunologic phenotypes that are likely to match without prolonged waiting times. However, as many as 50% of patients with incompatible donors will fail to find a match in a KPD pool and many of these patients could be desensitized to their donor. Positive crossmatch and ABO incompatible transplantation has been accomplished in selective cases without the need for heavy immunosuppression or B-cell ablative therapy. Patients who are both difficult-to-match due to broad sensitization and hard-to-desensitize because of strong donor reactivity can often be successfully transplanted through a combination of desensitization and KPD. Using these various modalities it is estimated that most patients with incompatible live donors can undergo successful renal transplantation.

BACKGROUND: We have monitored ABO antibody titers in 53 ABO-incompatible kidney transplants (INKTs) using a time-consuming, conventional test tube (CTT) method that included a 30-minute room temperature (RT) phase, followed by incubation for 30 minutes at 37 degrees C and conversion to the anti-human globulin (AHG) phase. Our studies have indicated that AHG ABO antibody titers are critical for clinical management, but RT titers do not supplement clinical decision making. Therefore, we assessed AHG titers by two methods: 1) a revised test tube (TT) method without RT and 2) an anti-immunoglobulin G (IgG) gel microcolumn (IgG gel) method with a goal of streamlining ABO antibody titrations. STUDY DESIGN AND METHODS: Fifty frozen samples from our INKT collection with anti-A and/or anti-B AHG titers of 2 to 512 were titrated by revised TT method with 30 minutes at 37 degrees C and conversion to AHG and by IgG gel method with 15 minutes at 37 degrees C and centrifugation. RESULTS: The titers using the revised TT and IgG gel methods had 64 and 52% concordance, respectively, with CTT AHG titers. Neither the revised TT AHG titers nor the IgG gel titers varied by more than one standard dilution from the CTT AHG titers, which is within acceptable limits for titration techniques. CONCLUSIONS: The revised TT and IgG gel titers are comparable to the CTT AHG titers. The IgG gel method offers the best titer turnaround time, eliminating 45 minutes of incubation time alone. Implementation of this technique would benefit ABO INKT patients by providing titer results in a more timely manner.

OBJECTIVE: No therapy except liver transplantation currently exists for patients with acute liver failure (ALF). The aim of this study was to determine whether pharmacologic mobilization of endogenous hematopoietic stem cells (HSCs) can aid in liver repair and improve survival in an animal model of ALF. METHODS: Rodents were treated with a single near-lethal intraperitoneal injection of carbon tetrachloride (CCl4). After 12 hours, animals were randomized to receive plerixafor and granulocyte colony-stimulating factor (G-CSF), agents known to mobilize marrow-derived stem cells, or saline vehicle injection. Mice were observed for survival, and serial assessment of liver injury by serum transaminase measurements, and histologic analysis was performed. RESULTS: In our ALF model, 7-day survival after injection of CCl4 was 25%. Administration of plerixafor and G-CSF following CCl4 resulted in 87% survival (n = 8, P < 0.05). On serial histopathologic analysis, animals treated with plerixafor and G-CSF demonstrated less hepatic injury compared with control animals. Evaluation of peripheral blood demonstrated an increase in circulating HSCs in response to plerixafor and G-CSF, and immunostaining suggested the infiltration of HSCs into the hepatic parenchyma after stem cell mobilization. CONCLUSIONS: Our results suggest a possible new treatment strategy for patients with ALF, a group for whom either liver transplantation or death is frequently the outcome. Pharmacologic agents that mobilize HSCs may lead to an infiltration of the injured liver with cells that may participate in or expedite liver regeneration. This therapy has the potential to avert liver transplantation in some patients with ALF and may be of benefit in a wide variety of medical and surgical patients with liver injury.