Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers.

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.

Graft survival of fourth-time renal transplant recipients is similar to third-time recipients: A SRTR database analysis.

BACKGROUND: Candidates for repeat kidney transplant (KT) have increased. While graft and patient survival are inferior to primary KT, second and third KTs improve patient survival over dialysis. Little is known about the outcomes after fourth KTs. METHODS: We retrospectively compared characteristics of third and fourth KTs in the SRTR. Factors associated with graft survival in third vs fourth KT and patient survival of fourth KT vs patients waitlisted for a 4th KT were assessed by Cox regression and multivariable linear regression analysis. RESULTS: There were 3055 third- and fourth-time KTs performed in the United States. Fourth-time graft survival was not significantly different from third-time transplants (HR 1.06, P = .653). Patients who received a fourth KT have a significant survival advantage compared with patients who remained on the waitlist for a fourth KT (HR = 0.53, P = .006). CONCLUSIONS: Graft and patient survival of fourth KTs are comparable to third KTs, but inferior to first and second KTs in terms of graft and patient survival. Recipients of fourth KT have had an increased life expectancy compared with patients waitlisted for a fourth KT.

Marijuana use should not preclude consideration for kidney transplantation.

Transplant eligibility for tobacco and/or marijuana using candidates varies among transplant centers. This study compared the impact of marijuana use and tobacco use on kidney transplant recipient outcomes. Kidney transplant recipients at a single center from 2001 to 2015 were reviewed for outcomes of all-cause graft loss, infection, biopsy-proven acute rejection, and estimated glomerular filtration rate between four groups: marijuana-only users, marijuana and tobacco users, tobacco-only users, and nonusers. The cohort (N = 919) included 48 (5.2%) marijuana users, 45 (4.8%) marijuana and tobacco users, 136 (14.7%) tobacco users, and 75% nonusers. Smoking status was not significantly associated with acute rejection, estimated glomerular filtration rate or pneumonia within one-year post-transplant in an adjusted model. Compared to nonuse, marijuana and tobacco use and tobacco-only use was significantly associated with increased risk of graft loss (aHR 1.68, P = .034 and 1.52, P = .006, respectively). Patients with isolated marijuana use had similar overall graft survival compared to nonusers (aHR 1.00, P = .994). Marijuana use should not be an absolute contraindication to kidney transplant.

Honoring patients' organ donation decisions when family conflict is present: Experience from a single organ procurement organization.

BACKGROUND: Donor designation refers to the laws and processes for documentation of an individual's wishes regarding organ donation should that person become eligible for donation at death. All 50 states have laws supporting donor designation. Donor-family conflict arises when a designated donor's family attempts to rescind the donor's authorization to donate. Little guidance exists in the current literature to address these situations. METHODS: Hospital public relations offices and organ procurement organization (OPO) records were queried to assess the incidence of legal action and adverse media coverage. Public legal records were searched for civil actions involving the hospitals at which these conflicts occurred. RESULTS: Fourteen cases of donor-family conflict were identified. Organ procurement proceeded in 9 (64%) of 14. A total of 38 organs were transplanted from these 9 donors. For those nine cases, median follow-up time was 57 months (interquartile range, 52-77 months; range, 38-114 months). The identified reasons for conflict include a belief by the family that they were given a choice in the decision about whether to proceed with donation; misunderstanding and lack of acceptance of the brain death diagnosis; disagreement among family members; concerns about timing/length of the donation process and desire to withdraw ventilator support; next-of-kin anger over cause of death when cause of death was suicide; and challenges to the validity of donor document and stated donor intent. No adverse news items were reported, and no lawsuits were filed in cases of donor-family conflict where organ donation proceeded. In addition, we found no mention of lawsuits brought against hospitals for failure to proceed with organ donation when donor was designated and eligible. CONCLUSION: The 2006 Anatomical Gift Act compels hospitals and OPOs to pursue donation regardless of family wishes in cases of brain death in designated donors. When a donor's family attempts to rescind the donor's authorization, the donor's wishes, not the families, should be honored. Fears of legal action and adverse media coverage are unfounded. Clinicians, OPO staff, and hospital administrators should strive to understand state donor designation law and create a plan for managing this conflict should it arise. LEVEL OF EVIDENCE: Therapeutic/care management study, level V.