Highly Sensitized Patients: Miami Transplant Institute Experience.

BACKGROUND: Transplantation continues to be challenging in highly sensitized patients. Herein, we compared induction immunosuppression (IS) based on immunologic risk stratification and desensitization with intravenous immunoglobulin (IVIG). METHODS: Of the 42 highly sensitized kidney and 3 kidney-pancreas transplant recipients who underwent IVIG for desensitization from 2008-2014, 10 (Control group) received standard induction IS with antithymocyte globulin, basiliximab, and methylprednisolone, and 35 (Rituximab group) received standard IS with rituximab ± IVIG ± plasmapheresis. Immunologic risk stratification was based on donor specific antibodies (DSA), flow crossmatch ratio, and calculated panel reactive antibody. All patients received tacrolimus, mycophenolate, and steroids for maintenance IS. Unacceptable antigen cut-offs for class I and II DSA were 6000 and 9000 mean fluorescence intensity and 2.0 and 4.4 channel shift ratios for T and B cell flow cytometry crossmatch, respectively. All complement dependent cytotoxicity T cell crossmatch negative patients were transplanted. RESULTS: Characteristics between groups, including high risk level, previous transplantation rate, number of human leukocyte antigen mismatches, delayed graft function rate, rejection rate, serum creatinine, and estimated glomerular filtration rate at 1 year (1.48 ± 0.6 and 50 ± 17 versus 1.1 ± 0.4 mg/dl and 66 25 ml/min) were not statistically significant between the Control and the Rituximab groups, respectively. Waiting time for the Control group was 6.4 years versus 4.1 years for the Rituximab group (p = 0.009). The cumulative proportion of patients who remain free of death or allograft failure was significantly higher in the Rituximab (87%) versus the Control group (60%) (p = 0.047). CONCLUSIONS: In highly sensitized patients who received desensitization with IVIG, the addition of Rituximab to our standard IS (and/or IVIG and plasmapheresis as per the immunologic risk stratification model) resulted in higher cumulative patient and graft survival.

Managing the kidney waiting list.

Candidates on the kidney transplant list wait for longer periods and have increasing numbers of comorbid conditions. To ensure that these candidates are acceptable for transplantation when an organ becomes available, physical, psychosocial, and financial strategies are essential. The authors surveyed 68 transplant centers to determine current practices. Eighteen percent of centers did not reevaluate candidates. Other programs used time on the list, disease, age, or a combination of these factors as evaluation criteria. Initial cardiac evaluation was relied upon by 51.4% of centers, with varying criteria used to determine status. Social work evaluation was done by 42.6% of centers, usually annually. Annual financial reevaluation was performed in 57.4%. Data support reviewing candidates, especially those with diabetes, those who have been receiving dialysis for a long time, and those older than 60 years. The dedication of one coordinator to manage waitlisted candidates using age, diagnosis, and time receiving dialysis was effective in this study.

Diagnosis of 6 mercaptopurine hepatotoxicity post liver transplantation utilizing metabolite assays.

Azathioprine and 6-mercaptopurine (6 MP) are commonly used as immunosuppression postsolid organ transplantation. Recently, a better understanding of the metabolism of these drugs has developed. 6 Mercaptopurine is metabolized by thiopurine methyl transferase (TPMT) which is under the control of a common genetic polymorphism. Genetic testing and measurement of levels of 6 MP metabolites allow identification of patients at risk of toxicity. We report two cases of cholestatic hepatocellular injury associated with 6 MP toxicity occurring after orthotopic liver transplantation. Cholestasis developed after the introduction of 6 MP. Patients underwent extensive investigation and 6 MP toxicity was considered only after all other causes had been excluded. Thiopurine methyl transferase alleles identified on genetic testing were normal as were the 6 thioguanine levels. However, 6-methyl mercaptopurine levels were significantly elevated into the toxic range. Cholestasis resolved within a few weeks of drug withdrawal. 6 Mercaptopurine hepatotoxicity can present with a variety of clinical, biochemical and histological manifestations post OLT and should be considered as a cause of liver enzyme elevation. Monitoring of 6 MP metabolite levels in addition to TPMT allele testing is useful to prevent 6 MP toxicity and to help guide therapy.

Survival and risk of recidivism in methadone-dependent patients undergoing liver transplantation.

Cirrhosis resulting from hepatitis C virus is presently the most common indication for liver transplantation (OLT) in the United States. A number of U.S. transplant centers require cirrhotics who are using methadone to discontinue it before proceeding with OLT. We sought to examine the outcomes of those patients who had undergone OLT at the Mount Sinai Medical Center. A retrospective chart review of 36 subjects on methadone maintenance treatment (MMT), and off heroin, at the time of OLT was performed. The median daily methadone dose pre-OLT was 50 mg. Post-OLT, there was an increase in methadone dose in 15 subjects, a decrease in four subjects, and no dose change in 17 subjects. Four subjects had documented single episodes of intravenous drug use post-OLT; only one subject had a dose change after the event. Patient and graft survival rates were comparable to the national average. There was no significant difference in post-OLT outcome in patients on MMT when compared with the general population. The few episodes of drug relapse were not related to changes in the methadone dose. Efforts should be made to allow methadone-using cirrhotics better access to OLT without regard to methadone dosage.

Living liver donors: a coordinator's perspective.

Living donor liver transplantation is an acceptable alternative for many patients awaiting a liver transplant. The benefits of living donor liver transplantation to the recipient are many; however, there is also an appreciable risk to the donor. Many people, including healthcare professionals, believe that living donor liver transplantation is not ethically justified because any risk to a donor outweighs the benefit to the recipient. Recent studies show adverse events in this population do not include only medical complications; any complication-medical, social, psychological, financial, or other--must be examined to analyze the true incidence of adverse outcomes in living liver donors.

Quality of life after lobectomy for adult liver transplantation.

INTRODUCTION: Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS: Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS: Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS: Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.