Cytomegalovirus Treatment in Solid Organ Transplantation: An Update on Current Approaches.

OBJECTIVE: The article reviews the safety and efficacy of treatments for cytomegalovirus (CMV) in solid organ transplantation. DATA SOURCES: A literature review was conducted in PubMed, MEDLINE, and Clinicaltrials.gov from database inception through January 2024, using terms CMV, therapy, and solid organ transplantation. STUDY SELECTION AND DATA EXTRACTION: Clinical trials, meta-analyses, cohort studies, case reports, and guidelines were included. Letters to the editor, reviews, and commentaries were excluded. DATA SYNTHESIS: After abstract screening and full-text review of 728 citations for eligibility, 53 were included. Valganciclovir and intravenous ganciclovir are drugs of choice for CMV management and, until recently, the availability of alternative options has been restricted due to toxicity. For instance, foscarnet and cidofovir serve as second-line agents due to potential bone marrow and renal toxicity. In patients with refractory or resistant CMV, maribavir, a novel oral agent, has proven efficacy and a lower adverse effect profile. However, in refractory or resistant CMV, foscarnet and cidofovir are preferred in invasive disease (CMV gastritis, CMV retinitis, and CMV encephalitis), high viral loads, and inability to tolerate oral preparations. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Consensus guidelines have not been revised since approval of novel antivirals in solid organ transplantation. Valganciclovir and ganciclovir remain drugs of choice for initial CMV therapy. Foscarnet, cidofovir, and maribavir are treatments for refractory or resistant-CMV. CONCLUSIONS: Selection of CMV antiviral treatment should be determined by patient-specific factors, including severity of illness, resistant or refractory disease, dose-limiting adverse effects, and the preferred route of administration.

Treatment of antibody-mediated rejection in renal transplant patients: a clinical practice survey.

INTRODUCTION: Preferences for the testing and treatment of antibody-mediated rejection (AMR) in renal transplant patients vary among programs and individual practitioners. The description of these preferences and identification of commonalities can contribute to creating a standard of care. METHODS: A survey was distributed through the Transplant Listserv of the American College of Clinical Pharmacy (ACCP) and via email to members of the American Society of Transplantation Community of Pharmacy (AST CoP), collected, and analyzed. RESULTS: Most clinicians (26/28) test for donor-specific antibodies (DSAs) when evaluating a patient with possible AMR. Treatments for AMR varied widely among responding clinicians and included intravenous immune globulin (IVIG, n = 25), plasmapheresis (n = 24), rituximab (n = 8), bortezomib (n = 4), rabbit antithymocyte globulin (n = 2), and eculizumab (n = 1). Weight-based dosing of IVIG averaged 1.8 g/kg total dose. Six centers use rituximab as initial therapy, while two use rituximab if other therapy fails. Four centers use bortezomib as initial therapy, while two centers use it for severe/persistent AMR. One center uses eculizumab as initial therapy and one center uses it for severe AMR. CONCLUSION: Methods for the detection of AMR are similar, yet treatment of AMR varies widely. Most centers utilize DSA for detection and a combination of IVIG and plasmapheresis for treatment.

Review of Objective Structured Clinical Examination Practices Within Pharmacy Programs Throughout the United States.

OBJECTIVE: To update the description of current objective structured clinical examination (OSCE) practices within pharmacy schools in the United States and identify barriers to OSCE implementation and expansion. METHODS: A survey was deployed to all accredited Doctor of Pharmacy programs within the United States. The survey was designed to collect information regarding the curricular mapping of OSCEs, OSCE design, OSCE delivery, assessment of OSCE performance, and barriers to OSCE implementation and expansion. RESULTS: Of the 135 US-accredited programs identified, 109 (81%) programs completed the survey. In total, 93 (85%) programs reported using OSCEs to assess students; however, implementation throughout the curriculum and current practices varied by institution. Most programs place OSCEs within specific courses (96%), with the applied skills coursework being the most used (80%). The most common number of OSCEs that occur throughout a curriculum is 6 (18%), however, 20 (22%) programs execute 10 or more OSCEs throughout their curriculum. Forty (43%) programs use OSCEs as high-stakes assessments where poor performance could prevent a student from progressing to advanced pharmacy practice experiences. Of the responding programs, over half (56%) use teaching objective structured examinations to enhance learning. Common barriers to OSCE expansion exist and are related to resource utilization. CONCLUSION: Significant expansion of OSCE development and implementation has occurred over the last decade. There is substantial variability in implementation and utilization among programs. Although standards of best practice for OSCEs exist for other health professions, best practices in pharmacy education have not been widely accepted or adopted.

A longitudinal exploration of perceptions of pharmacy practice preparedness among graduating pharmacy students and preceptors.

Graduating student pharmacists who are practice-ready is an essential responsibility of pharmacy programs and heavily emphasized by Accreditation Council of Pharmacy Education (ACPE), pharmacy education's accrediting body. Although several studies have examined students' readiness to engage in advanced pharmacy practice experiences (APPE), few studies examine graduating students' readiness to practice. The objective of this study was to examine national trends in graduating pharmacy students' and preceptors' perceptions of students' pharmacy practice preparedness across a six-year time frame (2016-2021) and trends in graduating students' overall impressions of their program and the pharmacy profession across the same time period. A longitudinal descriptive study to examine trends in graduating student and preceptor perception was conducted utilizing data from the 2016-2021 American Association of Colleges of Pharmacy (AACP) Graduating Student Surveys (GSS) (n = 65,461) and Preceptor Surveys (PS) (n = 41,951). Over six years of survey data analyzed, a large percentage of students at both public and private institutions reported they felt prepared for practice (96.5% vs 95.5% respectively, p < 0.001). There was overall agreement (>90%) among preceptors that graduating students were prepared to enter pharmacy practice based on responses, although preceptors had lower levels of agreement compared to students on most statements. Based on the findings, both graduating pharmacy students and preceptors feel that graduates are prepared to practice pharmacy, with consistent trends in perceptions over the last six years. However, results also indicate that a consistent downward trend in students' willingness to pursue pharmacy again, indicating decreased optimism of graduating students for the profession.

Perceptions and Utility of Course Evaluations in US Pharmacy Schools.

OBJECTIVE: This study aimed to describe the purpose, implementation, and perceived utility of course evaluations in pharmacy programs. METHODS: After a literature review, a 34-item survey was developed, pretested, and sent to assessment administrators at accredited pharmacy programs (N = 139) with at least 3 follow-ups. Descriptive and inferential statistics were performed in IBM SPSS Statistics software. RESULTS: A total of 90 programs responded (64.7% response rate). Most students (94%) were offered the opportunity to complete course evaluations. Some students completed evaluations during the course (47%), while others did so within 1 week of completion of the course (49%). Whether or not class time was given for students to complete the survey was often dependent on faculty choice (52.2%). Results were typically released after final grades were posted (92%), in time to use for the next semester of teaching (77%). Faculty were chosen to be evaluated by the number of teaching hours (50%) followed by all instructors (45.6%). Programs used the results for performance reviews by chairs (91%), course coordinator reviews (84%), and committee continuous quality improvement efforts (72%). Most programs did not provide faculty guidance on using evaluations (78%) nor development/mentoring (57%); only 22% of programs offered student development in completing evaluations. CONCLUSION: While most programs invite feedback from all students via evaluations, most did not provide guidance to faculty on how to use this feedback for faculty or course development purposes. A more robust process to optimize the use of course evaluations should be developed.

Selection of induction therapy in kidney transplantation.

Currently available immunosuppressive agents can be classified into three categories: induction agents, maintenance therapy, and treatment for rejection. This review article will focus on induction immunosuppression. There are three antibodies which are used for induction therapy: the lymphocyte-depleting agents - anti-thymocyte globulin and alemtuzumab, and basiliximab which is nondepleting. Historically, immunosuppressant selection was solely based on efficacy for prevention of rejection. In the current era of transplantation, it is now common practice in the transplant community to select induction therapy on the basis of risk-benefit considerations for each patient. This article will focus on the efficacy of available induction agents and the selection of induction agent based on donor and recipient risk factors.

Hidden sources of grapefruit in beverages: potential interactions with immunosuppressant medications.

PURPOSE: The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions. METHODS: A careful review of the ingredients of the 3 largest US beverage manufacturer's product lines was conducted through manufacturer correspondence, product labeling examination, and online nutrition database research. Focus was placed on citrus-flavored soft drinks, teas, and juice products and their impact on a patient's immunosuppressant regimens. RESULTS: Twenty-three beverages were identified that contained grapefruit. Five did not contain the word "grapefruit" in the product name. In addition to the confirmed grapefruit-containing products, 17 products were identified as possibly containing grapefruit juice or grapefruit extract. CONCLUSION: A greater emphasis should be placed upon properly educating patients regarding hidden sources of grapefruit in popular US beverages and the potential for food-drug interactions.

Racial, Ethnic, and Sex Diversity Trends in Health Professions Programs From Applicants to Graduates.

Importance: Diversity is an essential element of an effective health care system. A key to developing a diverse workforce is establishing a diverse student population in health professions programs. Objective: To examine the diversity of students in Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Doctor of Dental Surgery (DDS), Doctor of Dental Medicine (DMD), and Doctor of Pharmacy (PharmD) programs with emphasis on the trends of underrepresented minoritized groups (American Indian or Alaska Native, Black or African American, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander) and sex relative to the overall age-adjusted US population. Design, Setting, and Participants: This cross-sectional study used deidentified, self-reported data from 2003 to 2019 from the Association of American Medical Colleges, American Association of Colleges of Osteopathic Medicine, American Dental Education Association, American Dental Association, and American Association of Colleges of Pharmacy. Data analysis was performed from 2003 to 2004 and from 2018 to 2019. Exposures: Data on the race, ethnicity, and sex of applicants, matriculants, and degrees conferred by health professions programs were collected and compared with the age-adjusted population in the US Census (aged 20-34 years) over time. Main Outcomes and Measures: The main outcomes were trends in the proportions of underrepresented minoritized groups and sex diversity among applicants, matriculants, and degrees conferred relative to the overall age-adjusted US population. Trends were measured using the representation quotient, which is defined as the ratio of the proportion of each subgroup to the total population of applicants, matriculants, or graduates relative to the proportion for that subgroup within the US Census population of similar age. Regression analysis was used to evaluate the trend over time. Results: A total of 594 352 applicants were analyzed across the examined programs. From 2003 to 2019, the proportions of individuals from underrepresented groups increased for DDS and DMD (applicants, from 1003 of 8176 to 1962 of 11 298 [5.1%]; matriculants, from 510 of 4528 to 966 of 6163 [4.2%]; degrees awarded, from 484 of 4350 to 878 of 6340 [2.7%]), PharmD (applicants, from 9045 of 71 966 to 11 653 of 50 482 [9.0%]; matriculants, from 5979 of 42 627 to 10 129 to 62 504 [6.3%]; degrees awarded, from 922 of 7770 to 2190 of 14 800 [3.0%]), and DO (applicants, from 740 of 6814 to 3478 of 21 090 [5.4%]; degrees awarded, 199 of 2713 to 582 of 6703 [1.4%]) programs, but decreased for MD programs (applicants, from 6066 of 34 791 to 7889 of 52 777 [-2.3%]; matriculants, 2506 of 16 541 to 2952 of 21 622 [-2.4%]; degrees awarded, from 2167 of 15 829 to 2349 of 19 937 [-0.1%]). Compared with age-adjusted US Census data, all programs had more Asian students and fewer male, American Indian or Alaska Native, Black or African American, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander students (representation quotient <1). Conclusions and Relevance: In this cross-sectional study, most of the health professions in the study saw increases in underrepresented minority applicants, matriculants, and degrees conferred from 2003 to 2019; however, all programs were below the age-adjusted US Census data. The increased racial, ethnic, and sex diversity in the programs illustrates progress, but additional strategies are needed to achieve a more representative health care workforce.

Inhibitory interactions between BK and JC virus among kidney transplant recipients.

BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P=0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P=0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.

Serum sickness after treatment with rabbit antithymocyte globulin in kidney transplant recipients with previous rabbit exposure.

Serum sickness after rabbit antithymocyte globulin administration has a reported incidence of 7% to 27% in kidney transplant recipients. We describe 4 patients with previous exposure to rabbits who developed serum sickness after primary rabbit antithymocyte globulin induction. All patients presented with jaw pain. Three of 4 patients treated with plasmapheresis and steroids had prompt recovery, and 1 patient treated with steroids had slower recovery. We performed a telephone interview of 214 patients who contemporaneously underwent transplantation between November 2006 and July 2008 regarding rabbit exposure. More than half the patients had some type of previous rabbit exposure. There was a suggestion that patients with serum sickness were exposed more frequently to rabbits than those without. Jaw pain appears to be a hallmark symptom, and treatment with plasmapheresis and steroids relieves symptoms more rapidly than steroids alone.

A critique of validity analysis from instruments assessing the affective domain.

BACKGROUND: Schools and colleges of pharmacy need to show evidence that their students have internalized professional values, and many choose to do so through quantitative instruments. A review of the literature was completed to identify the evidence of validity of the scores from instruments designed to assess pharmacy students in the affective domain. METHODS: Electronic databases were searched to identify instruments. Basic information regarding the instruments, the facets of validity assessed, and the evidence for validity were reviewed. RESULTS: Of the studies identified, 25 focused on assessing the affective domain and reported evidence of at least one facet of validity. Most reported evidence of validity from two or more sources, and most reported evidence concerning test content and internal structure (i.e. internal consistency reliability or factor analysis). Other sources of validity were missing from most studies. IMPLICATIONS: More research is needed to investigate the validity of the scores of instruments developed to assess pharmacy students within the affective domain, especially regarding relations to other variables, response processes, and consequences of use.

Adverse drug reaction driven immunosuppressive drug manipulations: a single-center comparison of enteric-coated mycophenolate sodium vs. mycophenolate mofetil.

UNLABELLED: Enteric-coated mycophenolate sodium (MPS) has been developed to help circumvent the upper gastrointestinal side-effects of mycophenolic acid by facilitating drug release in the small intestine. Many questions regarding the side-effect profile of MPS remain. Therefore, the purpose of this study is to review a single-center's experience with mycophenolate mofetil (MMF) and MPS. METHODS: This retrospective, sequential cohort analysis of de novo renal and pancreas transplants (n = 198) compared MMF 500 mg b.i.d. to MPS 360 mg b.i.d. in conjunction with antibody induction, tacrolimus, and steroids. RESULTS: There were fewer adverse event driven drug manipulations in the MPS group at 90 d (4% MPS vs. 17% MMF) and 180 d (10% MPS vs. 24% MMF, p = 0.006, log-rank) after transplantation. There was a trend toward fewer GI-related hospital admissions in the MPS arm (7% MPS vs. 13% MMF, p = 0.18). Allograft outcomes including patient survival, graft survival, acute rejection, serum creatinine, and infection were similar. CONCLUSION: This single-center, sequential cohort study demonstrates that MPS is associated with fewer adverse event driven drug manipulations while maintaining similar safety and allograft outcomes.

Sirolimus conversion in liver transplant recipients with renal dysfunction: a prospective, randomized, single-center trial.

This pilot trial was designed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction. Forty patients with renal dysfunction (24-hr CrCl 40-80 mL/min) were randomized to be withdrawn from the calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control, P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection. Side effects of SRL were limited and included hyperlipidemia requiring treatment (15%), pruritus (5%), and mouth sores (25%). In this trial, SRL-based immunosuppression was a safe alternative to CNI. Although early improvements were observed, withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up.

Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure.

BACKGROUND: Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. METHODS: Using the United States Renal Data System, we identified 3,675 adult recipients (age >or=18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced <50%, reduced >or=50%, and MMF discontinued. Patients were followed until graft loss, death, last recorded immunosuppression prescription, or 3 years posttransplant. RESULTS: Compared to those with no MMF dose reductions or discontinuations, the risk of graft failure increased with MMF doses reduction >or=50% (HR=2.36, 95% CI 1.23-4.54) and those with MMF discontinuation (2.72, CI 1.60-4.64). CONCLUSION: Renal transplant recipients who underwent MMF dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.

Thymoglobulin induction is safe and effective in live-donor renal transplantation: a single center experience.

BACKGROUND: The relative benefit versus safety of induction therapy in live-donor renal transplant recipients is controversial. This paper presents observational data of live-donor recipients who received Thymoglobulin induction and standard maintenance immunosuppressive therapy. METHODS: Review and analysis of clinic records and electronic databases of live-donor renal transplants that received Thymoglobulin induction from May 1996 through 2003. RESULTS: Data analysis included 214 live-donor recipients (146 related, 68 unrelated) with a mean follow-up of 3.0+/-1.9 years. The average age of recipients was 44+/-13 years, with a majority being Caucasian (86%) and male (64%). Nineteen (9%) received previous transplants. No patients experienced delayed graft function and 10 (5%) developed acute rejection. Overall, predicted five-year patient survival was 96% and graft survival was 82%. The rates of CMV infection (5%), malignancy (3%), and lymphoproliferative disorder (0.5%) were low. When compared to live-donor kidney transplant recipients nationwide, the center cohort demonstrated improved five year patient (96% center versus 90% national, P=0.0326) and graft survival (82% center versus 79% national, P=0.0901), and a lower one-year acute rejection rate (2% center versus 21 % national, P<0.001). CONCLUSIONS: In this analysis, the use of Thymoglobulin in live-donor renal transplantation was associated with an absence of delayed graft function, low acute rejection rates, and high patient and graft survival without increasing the risk of infection or lymphoproliferative disorder.

Rabbit antithymocyte globulin induction therapy in adult renal transplantation.

Rabbit antithymocyte globulin (rATG) and horse antithymocyte globulin (horse ATG) are the polyclonal antithymocyte agents available for use in solid organ transplantation in the United States. Horse ATG is indicated for induction immunosuppression and for treatment of acute rejection episodes after kidney transplantation; rATG is indicated for treatment of acute rejection only. However, rATG is commonly used in clinical practice as an induction immunosuppressive agent, instigating many questions regarding appropriate dosing, tolerability, safety, and efficacy. Available evidence supports the use of rATG as an induction agent in adult renal transplant recipients. The use of this product for induction therapy has been studied in conjunction with a full-dose, triple-therapy maintenance regimen (sequential quadruple immunosuppression) consisting of a calcineurin inhibitor, an antimetabolite, and corticosteroids. Rabbit ATG has a proven safety and efficacy profile both as treatment of acute rejection and as induction therapy in patients undergoing kidney transplantation. The most common adverse events associated with rATG are cytokine release syndrome, thrombocytopenia, and lymphopenia. Results of early studies showed an increased rate of cytomegalovirus disease associated with rATG treatment, but recent studies indicate that routine administration of modern antiviral prophylaxis can reduce this risk. Current practice with rATG is evolving to minimize lifelong exposure to calcineurin inhibitors and corticosteroids.

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy.

BACKGROUND: Belatacept is a novel immunosuppressive therapy designed to improve clinical outcomes associated with kidney transplant recipients while minimizing use of calcineurin inhibitors (CNIs). METHODS: We searched for clinical trials related to administration of belatacept to kidney transplant patients compared to various immunosuppression regimens, as well as for studies that utilized data from belatacept trials to validate new surrogate measures. The purpose of this review is to consolidate the published evidence of belatacept's effectiveness and safety in renal transplant recipients to better elucidate its place in clinical practice. RESULTS: Analysis of the results from the Belatacept Evaluation of Nephroprotection and Effi-cacy as First-Line Immunosuppressive Trial (BENEFIT) study, a de novo trial that compared cyclosporine (CsA)-based therapy to belatacept-based therapy in standard criteria donors, found a significant difference in mean estimated glomerular filtration rate (eGFR) of 13-15 mL/min/1.73 m(2) and 23-27 mL/min/1.73 m(2) at 1 year and 7 years, respectively. The BENEFIT-EXT study was similarly designed with the exception that it included extended criteria donors. Renal function improved significantly for the more intensive belatacept group in all years of the BENEFIT-EXT study; however, it was not significant in the less intensive group until 5 years after transplant. Belatacept regimens resulted in lower blood pressure, cholesterol levels, and incidence of new-onset diabetes after transplant compared to CsA-based regimens. Results from conversion of CNIs to belatacept therapy, dual therapy of belatacept with sirolimus, and belatacept with corticosteroid avoidance therapy are also included in this article. CONCLUSION: The evidence reviewed in this article suggests that belatacept is an effective alternative in kidney transplant recipients. Compared to CNI-based therapy, belatacept-based therapy results in superior renal function and similar rates of allograft survival. In terms of safety, belatacept was shown to have lower incidence of hypertension, hyperlipidemia, and diabetes; however, incidence of posttransplantation lymphoproliferative disorder and the cost of belatacept may hinder use of this medication.

A randomized, prospective, pharmacoeconomic trial of tacrolimus versus cyclosporine in combination with thymoglobulin in renal transplant recipients.

BACKGROUND: To date, the clinical trials of tacrolimus (TAC) versus cyclosporine modified (CsA), have not defined which agent is more cost-effective for immunosuppression in renal transplant recipients especially in a quadruple immunosuppressive regimen. METHODS: The objective of this randomized, prospective study was to compare the clinical and economic outcomes of TAC versus CsA, in a regimen that consisted of Thymoglobulin induction, an antimetabolite, and prednisone. Between December 2000 and October 2002, 200 patients were enrolled and randomized in a 2:1 fashion (TAC n=134, CsA n=66). RESULTS: At 1 year, acute rejection (4% TAC vs. 6% CsA), patient survival (TAC 99% vs. CsA 100%), and graft survival (95% TAC versus 100% CsA, P=0.059) were similar. Serum creatinine levels were lower in the TAC group compared with the CsA group (1.3+/-0.3 vs. 1.6+/-0.7 mg/dL, P=0.03). The incidence of CMV infection was similar between the groups and two patients, both in the TAC arm, developed malignancy. Anti-hypertensive requirement (32% TAC vs. 32% CsA) and the incidence of posttransplant diabetes mellitus (4% TAC vs. 2% CsA) were similar. Pretransplant, fewer TAC patients received dyslipidemia treatment (40% TAC vs. 67% CsA, P=0.0005), while more CsA patients were able to discontinue these medications posttransplant (absolute change 25% TAC vs. 47% CsA). Total 12-month medication costs were similar (17,723 +/- 11,647 dollars TAC vs. 16,515 +/- 10,189 dollars CsA). CONCLUSIONS: When combined with Thymoglobulin induction, an antimetabolite, and corticosteroids, TAC and CsA are comparable in safety, efficacy, and cost in renal transplantation.

Sirolimus-induced leukocytoclastic vasculitis.

A 41-year-old white woman with cystic fibrosis underwent lung transplantion that was complicated by cyclosporine-induced nephrotoxicity, which required kidney transplantation. Three years after the renal transplant, sirolimus was substituted for mycophenolate mofetil in a maintenance immunosuppressive regimen that consisted of cyclosporine and prednisone, with the hope of lowering cyclosporine concentrations and avoiding the nephrotoxic effects. Three weeks after the initiation of sirolimus, the patient developed palpable purpura on the bilateral lower extremities that resolved after discontinuation of sirolimus and reappeared with rechallenge. Punch biopsy of the initial eruption revealed leukocytoclastic vasculitis with focal fibrinoid necrosis. Sirolimus should be considered as a causative agent of cutaneous leukocytoclastic vasculitis.

Cyclosporine minimization and cost reduction in renal transplant recipients receiving a C2-monitored, cyclosporine-based quadruple immunosuppressive regimen.

BACKGROUND: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels. METHODS: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and 1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between 100 and 250 ng/mL thereafter. RESULTS: Baseline patient and donor characteristics were similar. There were no differences in graft survival (100% C2 vs. 100% C0), acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6 months. C2 levels were lower than the suggested guidelines throughout the study (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were achieved in the C2 arm compared with the C0 arm by 1 month and were sustained throughout the trial, which translated into an average cyclosporine cost savings of USD $773 in the C2 arm during the 6-month period (P<0.001). CONCLUSION: With a quadruple immunosuppressive regimen and lower C2 targets than recommended for triple therapy, safe and effective cyclosporine minimization was achieved. Lower cyclosporine doses were achieved in C2-monitored patients compared with C0-monitored patients, translating into lower immunosuppressive costs.