Impact of high MELD scores on CMV viremia following liver transplantation.

INTRODUCTION: Advanced liver disease or cirrhosis is associated with an increased risk of infections; however, the impact of high pretransplant model for end-stage liver disease (MELD) score on cytomegalovirus (CMV) viremia after liver transplantation is unknown. METHODS: This single-center, retrospective, cohort study evaluated CMV high-risk (CMV immunoglobulin G D+/R-) liver transplant recipients who received valganciclovir prophylaxis for 3 months between 2009 and 2019. Patients were stratified by pretransplant MELD score of <35 (low MELD) and ≥35 (high MELD). The primary outcome was 12-month CMV viremia, and secondary outcomes included CMV resistance and tissue invasive disease, mortality, biopsy-proven acute rejection (BPAR), leukopenia, and thrombocytopenia. Multivariable Cox proportional-hazards modeling was used to assess the association of MELD score with the time to CMV viremia. RESULTS: There were 162 and 79 patients in the low and high MELD groups, respectively. Pretransplant MELD score ≥35 was associated with an increased risk of CMV viremia (hazard ratio [HR] 1.73; confidence interval 1.06-2.82, p = .03). CMV viremia occurred at 162 ± 61 days in the low MELD group and 139 ± 62 days in the high MELD group. Although BPAR occurred early at 30 days (13-59) in the low-MELD group and at 18 days (11-66) in the high-MELD group (p = .56), BPAR was not associated with an increased risk of CMV viremia (HR 1.55 [0.93-2.60], p = .1). DISCUSSION: MELD scores ≥35 were associated with an increased hazards of CMV viremia. In liver transplant recipients with MELD scores ≥35 who are CMV high-risk, additional CMV intervention may be warranted.

Survival benefit of renal transplantation in octogenarians.

BACKGROUND: Elderly patients are the fastest growing population requiring renal replacement therapy. As previous studies have shown a survival benefit of kidney transplantation compared to dialysis for end-stage renal disease, we sought to evaluate if this survival benefit extends to octogenarians. METHODS: This was a single-center retrospective cohort study of renal allograft recipients ≥80 years transplanted from 1999 to 2014 who were compared to patients listed during the same period that did not proceed to transplantation. A secondary matched group was selected from the UNOS transplant waitlist database. The primary outcome was patient survival. Secondary outcomes included graft survival and rejection incidence. RESULTS: Thirty-three transplanted patients were compared to 71 patients waitlisted at our center and 66 patients from the UNOS database. Patients in the study group were transplanted 20.8 ± 16.1 months after listing. Patient survival was 87.8% at 6 months and 1 year and 71.4% at 3 years. Kidney transplantation was associated with a significant decrease in the risk of death after listing (HR: 0.22, CI: 0.11-0.45, P < .001). CONCLUSION: With escalating life expectancy, kidney transplantation is a suitable treatment option in eligible octogenarians.

Interactions between anti-infective agents and immunosuppressants-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation provide an update on potential drug-drug interactions between anti-infectives and immunosuppressants, which are most notable with calcineurin and mTOR inhibitors. Drug-drug interactions may occur through pharmacokinetic mechanisms leading to altered drug concentrations of either the anti-infective or immunosuppressive drug, or by pharmacodynamic interactions increasing or decreasing the efficacy or toxicity of the medications. Many of the significant pharmacokinetic interactions occur through inhibition or induction of the cytochrome 3A4 system by anti-infective agents leading to increased or decreased immunosuppressive agent levels, respectively. The membrane transporter P-glycoprotein is also often involved in drug interactions. Since the last iteration of these guidelines, multiple new hepatitis C virus direct-acting antivirals have become available for use in SOT recipients. Of these agents, some are substrates of cytochrome and drug transporter systems, while others inhibit these systems and may affect immunosuppressive agents. Due to the high risk for drug-drug interactions in the solid organ transplant population, practitioners must be aware of potential interactions and be vigilant in monitoring and adjusting drug dosing when appropriate.

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts.

We performed a prospective, 12-month, single-center, nonrandomized, open-label pilot study to investigate the use of belatacept therapy combined with alemtuzumab induction in renal allografts with preexisting pathology, as these kidneys may be more susceptible to additional toxicity when exposed to calcineurin inhibitors posttransplant. Nineteen belatacept recipients were matched retrospectively to a cohort of tacrolimus recipients on the basis of preimplantation pathology. The estimated glomerular filtration rate was not significantly different between belatacept and tacrolimus recipients at either 3 or 12 months posttransplant (59 vs 45, P = 0.1 and 56 vs 48 mL/min/1.72/m2 , P = 0.3). Biopsy-proven acute rejection rates at 12 months were 26% in belatacept recipients and 16% in tacrolimus recipients (P = 0.7). Graft survival at 1 year was 89% in both groups. Alemtuzumab induction combined with either calcineurin inhibitor or costimulatory blockade therapies resulted in similar acceptable one-year outcomes in kidneys with preexisting pathologic changes. Longer-term follow-up may be necessary to identify preferential strategies to improve outcomes of kidneys at a higher risk for poor function (ClinicalTrials.gov-NCT01496417).

Clinical outcomes of valganciclovir prophylaxis in high-risk (D+/R-) renal transplant recipients experiencing delayed graft function.

BACKGROUND: Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear. METHODS: This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66). RESULTS: Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively. CONCLUSION: Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.

Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients.

BACKGROUND: Protease inhibitors (PI) pose a challenge post-transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non-interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI-based regimens on graft outcomes in HIV-infected renal transplant recipients. METHODS: In this retrospective cohort study, 50 HIV-infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003-2015 were analyzed. RESULTS: Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow-up, the overall risk of acute rejection in the PI group was 46% lower compared with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow-up time in the PI group. CONCLUSIONS: Our study suggests that PI-based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI-based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post-transplant.

Impact of Renal Replacement Therapy on Rejection among Liver Transplant Recipients.

Introduction: Renal dysfunction in liver transplant recipients is associated with an increased risk of morbidity and mortality, with an even higher risk among patients requiring renal replacement therapy. There is limited data evaluating rejection outcomes in patients requiring renal replacement therapy after liver transplant. Program evaluation aims: To evaluate the incidence of biopsy-proven acute rejection, recipient and graft survival, infection, renal dysfunction, and immunosuppression practices. Design: This was a single-center, retrospective, cohort study. To be eligible, patients were deceased donor liver transplant recipients ≥18 year of age transplanted between January 2017 and August 2019 who received steroid-only induction and tacrolimus as part of their initial immunosuppression regimen. Results: Recipients that required renal replacement therapy (N = 86) were compared to those who received no renal replacement therapy (N = 158). Biopsy-proven acute rejection at 1-year posttransplant was significantly higher among those requiring renal replacement therapy (36% vs 13%, P < .001). Patient survival at 12 months was 77% for those requiring renal replacement therapy and 94% for those not requiring renal replacement therapy (P < .001). Infection (HR 3.8, 95% CI 1.6-8.8; P < .001), but not rejection (HR 0.7, 95% CI 0.3-1.7; P = .5) was an independent predictor of mortality. The use of renal replacement therapy after liver transplant necessitated careful titration of immunosuppression to balance the detrimental risks of infection versus rejection in this high-risk population.

Impact of Steroid Only Induction on Rejection in Simultaneous Liver-Kidney Transplantation.

Introduction: The occurrence of simultaneous liver kidney transplantation has greatly increased; however, the ideal induction and maintenance immunosuppression remains unknown. Question: This evaluation aimed to determine if corticosteroid only induction in simultaneous liver kidney transplant recipients provided adequate prophylaxis against rejection when compared to basiliximab. Design: This was a single center, retrospective, cohort study of adult simultaneous liver kidney transplant recipients from June 2010 to June 2019 receiving corticosteroid only (N = 41) or basiliximab (N = 42) induction. Results: Liver or kidney biopsy proven acute rejection at 3 months was comparable between the corticosteroid only and basiliximab groups (10% vs 7%, P = .67), which persisted through 12 months posttransplant (15% vs 21%, P = .42). The occurrence of any infection at 3 months was increased in the corticosteroid only group relative to the basiliximab group (41% vs 21%, P = .049). Graft and patient survival at 12 months were similar between groups. Maintenance immunosuppression was overall minimized with a tacrolimus goal of 6-8 ng/mL, mycophenolate mofetil dose reduction to 1000 mg/day by 3 months, and early steroid withdrawal in both groups. Conclusion: Our findings suggested that corticosteroid only induction was an effective strategy for preventing rejection in simultaneous liver kidney transplant recipients, even in combination with reduced maintenance immunosuppression.

Personality: A potentially untapped resource in the selection of postgraduate pharmacy residents.

PURPOSE: This study assessed whether personality testing of postgraduate year 1 (PGY1) pharmacy residency applicants was feasible and predicted important selection outcomes, including interview offers. METHODS: Applicants to the PGY1 pharmacy residency program at a large academic medical center were invited to complete a 50-item online personality test based on the 5-factor model (ie, the "Big Five"). Scores were sealed until after matching, at which point they were compared to screening, interview, and ranking and match outcomes. Endpoints of interest included the feasibility of the test (eg, time required for completion, completion rate) and whether personality predicted the odds of an interview offer. RESULTS: The personality test was taken by 137 PGY1 applicants (69.5%) and required a median of 6.8 minutes to complete. Openness to experience was associated with decreased odds of an interview offer (adjusted odds ratio [OR], 0.86; 95% confidence interval [CI], 0.75-0.98), whereas conscientiousness and extraversion were associated with increased odds of an interview offer (conscientiousness: adjusted OR, 1.26; 95% CI, 1.02-1.55; extraversion: OR, 1.16; 95% CI, 1.03-1.31). When combined with traditional screening criteria (eg, awards, leadership positions), openness to experience and extraversion remained predictors of an interview offer (in the directions specified above), whereas conscientiousness did not. In an exploratory analysis of interviewees, agreeableness was a negative predictor of interview score. Personality did not predict screening scores or final ranking. CONCLUSION: Personality testing, based on the traits desired at individual residency programs, could be a valuable addition to the methods used for selecting PGY1 pharmacy residents.

Positive Patient Postoperative Outcomes with Pharmacotherapy: A Narrative Review including Perioperative-Specialty Pharmacist Interviews.

The influence of pharmacotherapy regimens on surgical patient outcomes is increasingly appreciated in the era of enhanced recovery protocols and institutional focus on reducing postoperative complications. Specifics related to medication selection, dosing, frequency of administration, and duration of therapy are evolving to optimize pharmacotherapeutic regimens for many enhanced recovery protocolized elements. This review provides a summary of recent pharmacotherapeutic strategies, including those configured within electronic health record (EHR) applications and functionalities, that are associated with the minimization of the frequency and severity of postoperative complications (POCs), shortened hospital length of stay (LOS), reduced readmission rates, and cost or revenue impacts. Further, it will highlight preventive pharmacotherapy regimens that are correlated with improved patient preparation, especially those related to surgical site infection (SSI), venous thromboembolism (VTE), nausea and vomiting (PONV), postoperative ileus (POI), and emergence delirium (PoD) as well as less commonly encountered POCs such as acute kidney injury (AKI) and atrial fibrillation (AF). The importance of interprofessional collaboration in all periprocedural phases, focusing on medication management through shared responsibilities for drug therapy outcomes, will be emphasized. Finally, examples of collaborative care through shared mental models of drug stewardship and non-medical practice agreements to improve operative throughput, reduce operative stress, and increase patient satisfaction are illustrated.

Comparison of Alemtuzumab Versus Basiliximab Induction Therapy in Elderly Kidney Transplant Recipients: A Single-Center Experience.

BACKGROUND: The optimal choice of induction immunosuppression for elderly kidney transplant recipients remains unclear. Although alemtuzumab has been associated with escalating risk of death and graft loss in this population, this risk has not been adequately explored. The purpose of this study was to compare the safety and efficacy of alemtuzumab with basiliximab induction in this population. METHODS: This is a retrospective matched cohort study of kidney transplant recipients aged ≥65 years. Patients who received alemtuzumab induction were matched (1:2) to a basiliximab control. The primary outcome was allograft survival. The incidence of acute rejection, infection, and all-cause mortality was measured. RESULTS: Fifty-one and 102 patients were included in the alemtuzumab and basiliximab groups, respectively. Baseline demographics were similar between groups, except for more living donor transplant recipients in the alemtuzumab group (26/51 [51%] vs 31/102 [30.4%], P = .02). Acute cellular rejection occurred more frequently within the first year in the basiliximab group (P = .02). There was no difference in rates of infection within the first year. Graft and patient survival rates were similar over the follow-up period. Patients receiving basiliximab had a higher glomerular filtration rate at 2 years posttransplant (59 mL/min/1.73 m2 vs 49 mL/min/1.73 m2, P = .03). CONCLUSIONS: Alemtuzumab induction is associated with similar outcomes to basiliximab in elderly kidney transplant recipients.

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation.

INTRODUCTION: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. RESEARCH QUESTION: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. DESIGN: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. RESULTS: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. DISCUSSION: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Successful Renal Transplantation between Identical Twins with Very Brief Immunosuppression.

Renal transplantation between monozygous identical twins provides an opportunity to utilize minimal immunosuppression to maintain stable allograft function, thereby alleviating the toxicities of immunosuppressive therapy. Despite monozygosity, there is a possibility of discordant protein presentation in identical twins that could trigger alloimmune response and lead to graft injury. Therefore, the optimal immunosuppression regimen in this patient population is unknown, and the safety of immunosuppression withdrawal remains controversial. Herein, we describe two patients who underwent successful renal transplantation from monozygotic identical twin donors. Monozygosity was determined using short tandem repeat (STR) analysis. All immunosuppression was successfully discontinued at 2 days and 3 weeks, respectively, after transplantation. Both patients are alive with functioning renal grafts at 1 year and 5 years after transplant, respectively. These two cases suggest that immunosuppression can be withdrawn safely and rapidly in select monozygous identical twin renal transplant recipients.

Collaborative practice agreement in solid organ transplantation.

Background Given the complexity of solid organ transplant recipients, a multidisciplinary approach is required. To promote medication safety and enable providers to focus on the medical and surgical needs of these patients, our department of pharmacy created a collaborative practice agreement between physicians and pharmacists. Through this agreement, credentialed pharmacists are empowered to provide inpatient services including initiation and adjustment of medications through independent review of laboratory results after multidisciplinary rounds. Objective To evaluate the effect of our collaborative practice agreement on clinical care and institutional finances. Setting An inpatient setting at a large academic medical center. Methods Three transplant pharmacists entered all clinical interventions made on abdominal transplant recipients between September and October 2013 into Quantifi®, a software application that categorizes and assigns a cost savings value based on impact and type of intervention. Main outcome measure The main outcome measures in this study were number and categorization of interventions, as well as estimated cost savings to the institution. Results There were 1060 interventions recorded, an average of 20 interventions per pharmacist per day. The most common interventions were pharmacokinetic evaluations (36%) and dose adjustments (19%). Over the time period, these interventions translated into an estimated savings of $107,634.00, or an annual cost savings of $373,131.20 per pharmacist, or a cost-benefit ratio of 2.65 to the institution. Conclusions Based on our study, implementation of a collaborative practice agreement enables credentialed pharmacists to make clinically and financially meaningful interventions in a complex patient population.