Long-term Outcomes Following a Comprehensive Quality Assurance and Process Improvement Endeavor to Minimize Opioid Use After Kidney Transplant.

Importance: Opioid use following kidney transplant is associated with an increased risk of graft loss and mortality. Opioid minimization strategies and protocols have shown reductions in short-term opioid use after kidney transplant. Objective: To evaluate the long-term outcomes associated with an opioid minimization protocol following kidney transplant. Design, Setting, and Participants: This single-center quality improvement study evaluated postoperative and long-term opioid use before and after the implementation of a multidisciplinary, multimodal pain regimen and education process in adult kidney graft recipients from August 1, 2017, through June 30, 2020. Patient data were collected from a retrospective chart review. Exposures: Preprotocol and postprotocol implementation use of opioids. Main Outcomes and Measures: Between November 7 and 23, 2022, opioid use before and after protocol implementation was evaluated up to 1 year after transplant using multivariable linear and logistic regression. Results: A total of 743 patients were included, with 245 patients in the preprotocol group (39.2% female and 60.8% male; mean [SD] age, 52.8 [13.1 years]) vs 498 in the postprotocol group (45.4% female and 54.6% male; mean [SD] age, 52.4 [12.9 years]). The total morphine milligram equivalents (MME) in the 1-year follow-up in the preprotocol group was 1203.7 vs 581.9 in the postprotocol group. In the postprotocol group, 313 patients (62.9%) had 0 MME in the 1-year follow-up vs 7 (2.9%) in the preprotocol group (odds ratio [OR], 57.52; 95% CI, 26.55-124.65). Patients in the postprotocol group had 99% lower odds of filling more than 100 MME in the 1-year follow-up (adjusted OR, 0.01; 95% CI, 0.01-0.02; P < .001). Opioid-naive patients postprotocol were one-half as likely to become long-term opioid users vs preprotocol (OR, 0.44; 95% CI, 0.20-0.98; P = .04). Conclusions and Relevance: The study's findings show a significant reduction in opioid use in kidney graft recipients associated with the implementation of a multimodal opioid-sparing pain protocol.

Impact of CYP3A5 genotype on de-novo LCP tacrolimus dosing and monitoring in kidney transplantation.

OBJECTIVES: LCP tac has a recommended starting dose of 0.14 mg/kg/day in kidney transplant. The goal of this study was to assess the influence of CYP3A5 on perioperative LCP tac dosing and monitoring. METHODS: This was a prospective observational cohort study of adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele). RESULTS: In this study, 120 were screened, 90 were contacted and 52 provided consent; 50 had genotype results, and 22 patients expressed CYP3A5*1. African Americans (AA) comprised 37.5% of nonexpressors versus 81.8% of expressors (P = 0.001). Initial LCP tac dose was similar between CYP3A5 groups (0.145 vs. 0.137 mg/kg/day; P = 0.161), whereas steady state dose was higher in expressors (0.150 vs. 0.117 mg/kg/day; P = 0.026). CYP3A5*1 expressors had significantly more tac trough concentrations of less than 6 ng/ml and significantly fewer tac trough concentrations of more than 14 ng/ml. Providers were significantly more likely to under-adjust LCP tac by 10 and 20% in CYP3A5 expressors versus nonexpressors (P < 0.03). In sequential modeling, CYP3A5 genotype status explained the LCP tac dosing requirements significantly more than AA race. CONCLUSION: CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers.