Comparing weight-based dosing of tacrolimus XR in obese and non-obese renal transplant recipients.

The recommended initial weight-based dose of extended-release (XR) tacrolimus (Envarsus XR) in kidney transplant recipients (KTR) is 0.14 mg/kg/day. However, no data exist regarding dosing recommendations for obese patients specifically. The aim of this study was to evaluate weight-based dosing requirements in a cohort of obese KTR who were initiated on de novo tacrolimus XR post-transplantation. The primary outcome was weight-based dosing requirements (mg/kg/day) on post-operative day (POD) 7 and 14. Of the 254 KTR, 81 (31%) were obese. The median therapeutic dose on POD7 was 0.1 versus 0.12 vs. 0.14 mg/kg/day in the BMI > 30 kg/m2 , BMI 25-30 kg/m2 , and BMI < 25 kg/m2 , respectively, (p = .0001). This result was similar on POD14; median therapeutic dose was 0.09 versus 0.11 versus 0.15 mg/kg/day in the BMI > 30 kg/m2 , BMI 25-30 kg/m2 , and BMI < 25 kg/m2 , respectively, (p < .001). Therapeutic dose on POD7 and POD14 based on ideal body was similar in all cohorts (p = .238, p = .923, respectively). This finding was supported by a strong linear relationship between ideal body weight (IBW) and therapeutic dose (r = .929). In both obese and non-obese KTR, IBW had a stronger correlation with the therapeutic dose for tacrolimus XR.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

Concomitant tacrolimus and ketorolac therapy in pediatric liver transplant recipients: Teaching old dogma new tricks.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ketorolac, are effective analgesic medications, but concerns for nephrotoxicity have limited their role for pain control following pediatric liver transplantation (LT). Calcineurin inhibitors (CNIs) and NSAIDs share a similar mechanism of nephrotoxicity, and concomitant administration is traditionally discouraged. A retrospective review of pediatric LT recipients was conducted between 1/1/2015 and 12/31/2019 at a single center. Patients were stratified based on receipt of ketorolac. The primary outcome was the incidence of acute kidney injury (AKI). Secondary outcomes included serum creatinine, urine output, estimated glomerular filtration rate, bleeding incidence, oral morphine milligram equivalents, and hospital length of stay (LOS). The incidence of AKI was similar between the two groups with 25.8% of patients in the ketorolac group versus 29.2% of patients in the nonketorolac group (p = .475) meeting criteria in the first 10 days post-transplant. Opioid requirements were less in the ketorolac group (p < .001), who also demonstrated shorter LOS compared with nonketorolac patients (p = .033). Concurrent CNI and ketorolac use did not result in an increased incidence of AKI in the early post-LT period and resulted in significantly lower opioid requirements along with a decreased hospital LOS.

Adherence, Medical Outcomes, and Health Care Costs in Adolescents/Young Adults Following Pediatric Liver Transplantation.

OBJECTIVE: Improved outcomes after pediatric liver transplantation (LT) have led to increasing numbers of adolescent and young adult recipients entering into adult health care systems. The aim of this study was to evaluate the impact of transition from pediatric to adult health care models on medical outcomes, measures of adherence, and health care utilization for pediatric LT recipients. METHODS: We evaluated the course of patients who received an LT while followed in pediatrics and transferred to an adult care provider within our institution. Data were collected from 2 years preceding and 2 years following transfer of care. RESULTS: A total of 32 patients were eligible for analysis. Median age at time of transfer was 22.9 years (interquartile range 21.7-23.6). Nine patients (28%) died following transfer of care. There was a significant decrease in office visit adherence following transfer of care (P = 0.02). Although not achieving significance, an increase in alanine aminotransferase values, episodes of acute cellular rejection, progression to cirrhosis, evolution to chronic rejection, and hospital admission rates post transfer were found. These findings were associated with an increase in health care costs related to required interventions. CONCLUSIONS: Our study demonstrates trends toward worse health outcomes, decreased adherence, and increased health care utilization following transfer of care. These findings and poor patient survival suggest that the time around transition from pediatric to adult health care models represents a period of increased vulnerability for pediatric LT recipients. Larger, multicenter, prospective studies are needed to identify factors and interventions that affect adolescent and young adult to improve the transition process.

The effect of race coefficients on preemptive listing for kidney transplantation.

Background: Race coefficients of estimated glomerular filtration rate (eGFR) formulas may be partially responsible for racial inequality in preemptive listing for kidney transplantation. Methods: We used the Scientific Registry of Transplant Recipients database to evaluate differences in racial distribution of preemptive listing before and after application of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) race coefficients to all preemptively listed non-Black kidney transplant candidates (eGFR modulation). Odds of preemptive listing were calculated by race, with Black as the reference before and after eGFR modulation. Variables known to influence preemptive listing were included in the model. Results: Among 385 087 kidney-alone transplant candidates from 1 January 2010 to 2 December 2020, 118 329 (30.7%) candidates were identified as preemptively listed (71.7% White, 19% Black, 7.8% Asian, 0.6% multi-racial, 0.6% Native American and 0.3% Pacific Islander). After eGFR modulation, non-Black patients with an eGFR ≥20 mL/min/1.73 m2 were removed. Compared with Black candidates, the adjusted odds of preemptive listing for White candidates decreased from 2.01 [95% confidence interval (95% CI) 1.78-2.26] before eGFR modulation to 1.18 (95% CI 1.0-1.39; P = 0.046) with the MDRD and 1.37 (95% CI 1.18-1.58) with the CKD-EPI equations after adjusting for race coefficients. Conclusions: Removing race coefficients in GFR estimation formulas may result in a more equitable distribution of Black candidates listed earlier on a preemptive basis.

Prior Amiodarone Exposure Reduces Tacrolimus Dosing Requirements in Heart Transplant Recipients.

INTRODUCTION: Amiodarone use prior to heart transplant is independently associated with a higher rate of severe primary graft dysfunction and in-hospital mortality. Amiodarone may also alter the pharmacokinetics of medications metabolized via cytochrome P450. No data exist regarding the interaction between pretransplant amiodarone and tacrolimus concentrations. DESIGN: Single-center retrospective study of transplant patients between January 1, 2014, and June 30, 2016. A therapeutic tacrolimus concentration was defined as a trough level between 8 and 15 ng/mL for 2 consecutive days. The primary outcome was the tacrolimus therapeutic weight-based dosing requirements (mg/kg/day) for patients receiving amiodarone prior to transplant when compared to those without prior receipt of amiodarone. Secondary outcomes include the incidence of cellular rejection and mortality within 6 months posttransplant. RESULTS: Multi-organ transplant recipients (n = 3), retransplants (n = 9), those who died prior to a therapeutic level (n = 1), and those receiving amiodarone posttransplant (n = 7) were excluded from the analysis. Of the 80 patients included, 34 (42%) received amiodarone prior to transplant. Patient characteristics were similar, with the exception of primary graft dysfunction incidence (38% in amiodarone vs 8.5% in control, P = .001). The median therapeutic dose was 0.1 (interquartile range [IQR]: 0.07-0.12) versus 0.13 (IQR: 0.09-0.17) in the amiodarone and control groups, respectively, ( P < .01). No significant difference in mortality or rejection was noted. CONCLUSION: Patients receiving amiodarone prior to transplant require a lower weight-based dose of tacrolimus.