Evaluation of Tacrolimus Concentrations and Clinical Outcomes Between Extended and Immediate Release Formulations in Kidney Transplant.

Objectives: Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. Methods: This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. Results: 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, P = .63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. Conclusions: The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes.

Early versus delayed initiation of cytomegalovirus prophylaxis after liver transplant.

OBJECTIVES: Delaying cytomegalovirus (CMV) prophylaxis after liver transplantation may limit medication side effects and reduce inpatient drug costs. The primary objective of this study was to determine the incidence of CMV DNAemia in liver transplant recipients who initiated prophylaxis immediately after transplant (early prophylaxis) and those who initiated prophylaxis on postoperative day 7 or at discharge, whichever came first (delayed prophylaxis). STUDY DESIGN: This was a retrospective, single-center study of adult liver transplant recipients between February 2017 and February 2019. Patients who were at low risk for CMV (D-/R-), received dual organs, had a history of invasive CMV disease, or received prophylaxis with an agent other than ganciclovir/valganciclovir were excluded. Chart review of patient profiles was completed 9 months following the transplant, and the primary end point was the first positive CMV PCR within that timeframe. Cumulative incidence of CMV DNAemia was estimated by adjusting for competing events for early and delayed prophylaxis groups. The subdistribution hazard model was utilized to examine the effect of the timing of prophylaxis on CMV DNAemia while accounting for CMV serostatus. Secondary end points included peak quantifiable viral load, time to detection, and incidence of tissue-invasive disease. RESULTS: A total of 119 patients (60 early prophylaxis and 59 delayed prophylaxis) were included, and baseline demographics were similar except for sex. Twenty patients in the early group and 17 in the delayed group developed CMV DNAemia within 9 months of transplant with a cumulative incidence of 31.7% (95% confidence interval (CI) 20%, 44%) and 28.8% (95% CI 18%, 41%), respectively. After controlling for CMV serostatus, the relative incidence of DNAemia was similar between prophylaxis groups (subdistribution hazard ratio: 1.01, 95% CI 0.53, 1.90). CONCLUSIONS: No significant difference in CMV DNAemia within 9 months of liver transplant was observed between patients who received early and delayed prophylaxis. Future studies are warranted to conclude that delaying prophylaxis can be considered a safe alternative to initiating prophylaxis immediately after transplant.

Delayed vs initial cytomegalovirus prophylaxis after kidney transplantation.

It is recommended to start cytomegalovirus (CMV) prophylaxis within 10 days of solid organ transplant, if indicated. Our center underwent a cost-savings initiative to delay CMV prophylaxis initiation from postoperative day zero to postoperative day 7 or upon discharge, hypothesizing this would not affect clinical outcomes but could impact costs. The purpose of this retrospective study was to determine the effects of early vs delayed (<72 vs >72 hours after transplant) CMV prophylaxis in kidney and kidney/pancreas transplant recipients transplanted between June 2014 and January 2017. The primary endpoint was incidence of CMV infection within 1 year. Secondary endpoints included CMV disease, CMV testing, and valganciclovir cost during index hospitalization. A total of 173 patients (114 early, 59 delayed) were included. CMV infection occurred in 61% vs 54% in the early vs delayed group (P = .5). Excluding low-level DNAemia (QNAT < 200 IU/mL), infection occurred in 30% vs 22% in the early vs late group (P = .4). The median days to starting prophylaxis were 0 and 6 in the early and delayed group (P < .05), which led to a median cost savings of $497.00 per patient during index hospitalization (P < .05). Delaying prophylaxis initiation did not impact CMV outcomes in this cohort and decreased costs.

Effects of Ideal Versus Total Body Weight Dosage of Rabbit Antithymocyte Globulin on Outcomes of Kidney Transplant Patients With High Immunologic Risk.

OBJECTIVES: The optimal dose of rabbit antithymocyte globulin induction therapy in kidney transplant recipients with high immunologic risk lacks consensus. The purpose of this study was to evaluate the effect of using ideal body weight rather than total body weight for the weight-based dose calculations in this patient population. MATERIALS AND METHODS: Data were retrospectively collected on 89 adult patients who received rabbit antithymocyte globulin induction therapy for high immunologic risk kidney transplant. Hospital protocol changed from the use of cumulative rabbit antithymocyte globulin doses of 7.5 mg/kg total body weight to 7.5 mg/kg ideal body weight in 2009. Patients were separated into 2 cohorts based on the amount of rabbit antithymocyte globulin (in mg/kg total body weight) received. Rate of biopsy-proven acute rejection, patient survival, and allograft function were evaluated at 90 days and 1 year after transplant. Cost of induction therapy was also evaluated. RESULTS: Baseline demographics were predominantly similar between the 2 cohorts. No significant difference in maintenance immunosuppression was identified. Rates of biopsy-proven acute rejection at 90 days and 1 year were similar between ideal and total body weight cohorts (4.2% vs 0% at 90 days, P = .5; 8.7% vs 0% at 1 year, P = .13). Patient survival and allograft function were also similar. Median cost of rabbit antithymocyte globulin induction therapy per patient was lower in the ideal body weight cohort, but this difference was not statistically significant ($17 542 vs $19 934; P = .3). CONCLUSIONS: Our results suggest that use of ideal body weight for dose calculations of rabbit antithymocyte globulin induction therapy in high immunologic risk kidney transplant recipients at 7.5 mg/kg results in low rates of acute rejection with a safety profile similar to that shown with a total body weight dosage. Use of ideal body weight for lower cumulative doses may still need further evaluation in this patient population.

Role of gabapentin in the treatment of uremic pruritus.

OBJECTIVE: To evaluate the efficacy of gabapentin for the treatment of uremic pruritus (UP). DATA SOURCES: Literature retrieval was accessed through MEDLINE (1950-March week 3, 2008; In-Process & Other Non-Indexed Citations, April 1, 2008) and International Pharmaceutical Abstracts (1970-March 2008) using the terms gabapentin, pruritus, itch, urem$ (truncated), dialysis, and kidney disease. The Google Scholar search engine was used to identify articles that MEDLINE did not capture with the described search terms. Additionally, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English and studies conducted in humans were identified and evaluated. DATA SYNTHESIS: UP is an unpleasant itching sensation that affects approximately 30% of patients on hemodialysis (HD). The current mainstays of therapy include antihistamines and topical therapies, although many patients remain symptomatic despite these treatments. Alternative therapeutic approaches, including topical, oral, and intravenous drugs; dialysis modifications; homeopathic therapies; and physical treatments have been used, but few evidence-based studies exist to support their utility. Gabapentin has been evaluated for the treatment of UP in 2 small, randomized, placebo-controlled studies, 1 pilot evaluation, and 1 index case. Gabapentin has demonstrated efficacy in the treatment of multiple types of itch and shows promise in treating patients with UP who are unresponsive to standard therapies. All of the controlled studies consisted of 4 weeks of active treatment, and no patients discontinued gabapentin due to adverse events. The most common adverse events noted in these trials were consistent with gabapentin's safety profile (dizziness, somnolence, fatigue, nausea). CONCLUSIONS: Available data support the use of gabapentin as a well-tolerated and effective treatment option for patients with UP who are unresponsive to traditional therapies. Further well-designed trials are warranted to establish the most appropriate dosing regimen in patients on HD.