Electronic health record-enabled routine assessment of medication adherence after solid organ transplantation: the time is now.

Medication nonadherence after solid organ transplantation is recognized as an important impediment to long-term graft survival. Yet, assessment of adherence is often not part of routine care. In this Personal Viewpoint, we call for the transplant community to consider implementing a systematic process to screen and assess medication adherence. We believe acceptable tools are available to support integrating adherence assessments into the electronic health record. Creating a standard assessment can be done efficiently and cost-effectively if we come together as a community. More importantly, such monitoring can improve outcomes and strengthen provider-patient relationships. We further discuss the practical challenges and potential rebuttals to our position.

The measure of impact: Proposal of quality metrics for solid organ transplant pharmacy practice.

As healthcare continues its transition toward value-based care, it is increasingly important for transplant pharmacists to demonstrate their impact on patient care, health-related outcomes, and healthcare costs. Evidence-based quality and performance metrics are recognized as crucial tools for measuring the value of service. Yet, there is a lack of well-developed and agreed-upon specific metrics for many clinical pharmacy specialties, including solid organ transplantation. To address this need, a panel of transplant pharmacy specialists conducted a detailed literature review and engaged in several panel discussions to identify quality metrics to be considered for assessing the value of clinical pharmacy services provided to solid organ transplant recipients and living donors. The proposed metrics are based on the Donabedian model and are categorized to coincide with the typical phases of transplant care. The measures focus on key issues that arise in transplant recipients related to medication therapy, including adverse drug events, nonadherence, and clinical outcomes attributable to medication therapy management. This article proposes a comprehensive set of measures, any number of which transplant pharmacists can adopt and measure over time to objectively gauge the value of services they are providing to transplant recipients, the transplant center, and the overall healthcare system.

Benefits of early vascular provider involvement in wound care center management of patients with underlying arterial disease.

OBJECTIVES: Peripheral arterial disease (PAD) can reduce wound healing rates by ≤30%. Current literature suggests wound outcomes are improved when management is driven by vascular providers. However, whether this benefit is derived solely from early vascular provider involvement remains unclear. METHODS: A retrospective analysis was performed of 80 limbs with chronic wounds and underlying PAD seen at our institution's wound center between July 2022 and July 2023. Arterial disease was defined by the following criteria: (1) prior PAD diagnosis, (2) ankle-brachial-index of <0.9 or toe pressure of <70 mm Hg, or (3) absent peripheral pulses. Patients were divided into early (<6 week) vascular provider exposure (EVE; n = 45) or late/no vascular exposure (LNVE; n = 35). Providers included vascular surgeons and affiliated advanced practitioners. The primary outcome studied was overall time to wound healing. Statistical analysis included χ2 tests, t test, Pearson correlation, Kaplan-Meier analysis, and Cox regression modeling (variables included in a multivariate model if univariate effect on healing was associated at P < .1). RESULTS: Baseline demographic profiles were similar between groups with exception of lower baseline albumin (P = .037), more heart failure (P = .013), and more prior peripheral endovascular interventions (P = .013) in the EVE group. Although the initial wound locations and sizes were similar, EVE wounds had significantly higher WIfI wound scores (1.9 ± 0.1 vs 1.6 ± 0.1; P = .039). Although more LNVE patients developed radiographic osteomyelitis (31.8% vs 55.6%; P = .033), fewer underwent operative debridement or amputation (100% vs 63.2%; P = .008). On univariate analysis, healing time tended to be shorter in EVE, but not significantly (P = .089). When controlled for comorbidities, however, healing rates were nearly two-fold higher in EVE (hazard ratio, 2.42; 95% confidence interval, 1.21-4.84). LNVE wounds also took significantly longer to reach checkpoints including time to >75% granulation (P = .05), 15% weekly size decrease (P = .044), and epithelialization (P = .026). LNVE patients required more wound center visits (P = .024) and procedures (P = .005) with a longer time to intervention (P = .041). All EVE patients obtained ankle-brachial indices, with 90.9% of them available at their first wound care visit (P < .001). Although a slightly greater proportion of patients underwent a major amputation in EVE (15.6% vs 11.4%; P = .595), this difference did not attain significance; additionally, 100% of EVE patients had documented discussion of nonsalvageable limbs before amputation. CONCLUSIONS: Early exposure to vascular practitioners improves wound healing time, timeliness to intervention, and wound center and hospital resource use in patients with PAD. Further investigation into benefits of vascular involvement within community wound center models could significantly improve awareness and accessibility of arterial wound care in smaller/remote communities.

Medication Safety Events After Acute Myocardial Infarction Among Veterans Treated at VA Versus Non-VA Hospitals.

INTRODUCTION: Fragmentation of health care across systems can contribute to mistakes in prescribing and filling medications among patients treated for myocardial infarction (MI). We sought to compare omissions, duplications, and delays in outpatient medications used for secondary prevention among veterans treated for MI at Veterans Affairs (VA) versus non-VA hospitals. METHODS: We utilized national VA and Centers for Medicare and Medicaid Services data (2012-2018) to identify veterans 65 years or older hospitalized for MI and measured the use of outpatient medications for secondary prevention in the 30 days after MI among those treated at VA versus non-VA hospitals. RESULTS: A total of 118,456 veterans experiencing MI were included; of which 102,209 were hospitalized at non-VA hospitals. An omission in any medication class occurred more frequently among veterans treated at non-VA versus VA hospitals (82.8% vs 67.8%, P < 0.001). In multivariable modeling, the odds of omissions in any medication class were higher among those treated at non-VA versus VA hospitals (odds ratio: 3.04; 95% CI: 2.88-3.20). Duplications occurred more frequently in veterans treated at non-VA versus VA hospitals: 1.9% versus 1.6% had 1 or more for non-VA versus VA hospitals ( P < 0.001). Veterans treated at non-VA hospitals were more likely to have delays of 3 days or more in prescription fills after hospital discharge (88.4% vs 70.6% across all classes, P < 0.001). CONCLUSIONS: Omissions, duplications, and delays in outpatient prescribing of secondary prevention medications were more common among 118,456 veterans treated at non-VA versus VA hospitals for MI. Interventions aimed at improving care transitions and optimizing medication use among veterans treated at non-VA hospitals should be implemented.

Evolving trends in immunosuppression use and cytomegalovirus infection risk over the past decade in kidney transplantation.

BACKGROUND: The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years. METHODS: This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses. RESULTS: Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8 ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years.  Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8 ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500 mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection. CONCLUSION: Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV.  A more individualized immunosuppression regimen based on infection risk merits consideration.

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.

Results of a multicenter cluster-randomized controlled clinical trial testing the effectiveness of a bioinformatics-enabled pharmacist intervention in transplant recipients.

An ambulatory medication safety dashboard was developed to identify missing labs, concerning labs, drug interactions, nonadherence, and transitions in care. This system was tested in a 2-year, prospective, cluster-randomized, controlled multicenter study. Pharmacists at 5 intervention sites used the dashboard to address medication safety issues, compared with usual care provided at 5 control sites. A total of 2196 transplant events were included (1300 intervention vs 896 control). During the 2-year study, the intervention arm had a 11.3% (95% confidence interval, 7.1%-15.5%) absolute risk reduction of having ≥1 emergency department (ED) visit (44.2% vs 55.5%, respectively; P < .001, respectively) and a 12.3% (95% confidence interval, 8.2%-16.4%) absolute risk reduction of having ≥1 hospitalization (30.1% vs 42.4%, respectively; P < .001). In those with ≥1 event, the median ED visit rate (2 [interquartile range (IQR) 1, 5] vs 2 [IQR 1, 4]; P = .510) and hospitalization rate (2 [IQR 1, 3] vs 2 [IQR 1, 3]; P = .380) were similar. Treatment effect varied by comorbidity burden, previous ED visits or hospitalizations, and heart or lung recipients. A bioinformatics dashboard-enabled, pharmacist-led intervention reduced the risk of having at least one ED visit or hospitalization, predominantly demonstrated in lower risk patients.

The expanded role of the transplant pharmacist: A 10-year follow-up.

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.

A viewpoint describing the American Society of Transplantation rationale to conduct a comprehensive patient survey assessing unmet immunosuppressive therapy needs.

This viewpoint aims to "set the stage" and provide the rationale for the proposed development of a large-scale, comprehensive survey assessing transplant patients' perceived unmet immunosuppressive therapy needs. Research in organ transplantation has historically focused on reducing the incidence and impact of rejection on allograft survival and minimizing or eliminating the need for chronic immunosuppressive therapies. There has been less emphasis and investment in therapies to improve patient-reported outcomes including health-related quality of life and side-effects. Patient-focused drug development (PFDD) is a new and important emphasis of the Food and Drug Administration (FDA) that provides a guiding philosophy for incorporating the patient experience into drug development and evaluation. The American Society of Transplantation (AST) Board of Directors commissioned this working group to prepare for the conduct of a comprehensive patient survey assessing unmet immunosuppressive therapy needs. This paper aims to describe the basis for why it is important to conduct this survey and briefly outline the plan for broad stakeholder engagement to ensure the information gained is diverse, inclusive, and relevant for advancing PFDD in organ transplant recipients.

Impact of obesity on the conversion of immediate-release tacrolimus to extended-release tacrolimus in kidney transplant recipients.

Outcomes analyzing conversion from IR-tacrolimus (IR) to LCP-tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight-based dose at a steady-state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection. A total of 292 patients were included; 156 and 136 patients with a BMI < 30 and BMI ≥ 30 kg/m2 , respectively. Baseline characteristics were similar, except for pancreas transplant, diabetes, and HLA mismatch. IR to LCP conversion ratio ranged from .73 to .79. Mean LCP dose was similar (.08 vs. .07 mg/kg/day for BMI < 30 and BMI ≥ 30 kg/m2 , respectively); there was a significant difference in IR and LCP mg/kg dosing at steady state with TBW (.11 mg/kg vs.09 mg/kg and .08 mg/kg vs. .06 mg/kg, respectively). The most appropriate dosing weight was adjusted body weight (AdjBW), consistent across IR and LCP steady-state doses, and might yield more accurate steady-state dosing requirements. In multivariable modeling, BMI was a significant predictor of steady state mg/kg dosing at therapeutic goal for total body weight (TBW), but not ideal body weight (IBW) or AdjBW.

Impact of converting adult kidney transplant recipients with high tacrolimus variability from twice daily immediate release tacrolimus to once daily LCP-Tacrolimus.

BACKGROUND: The influence of converting to once daily, extended-release LCP-Tacrolimus (Tac) for those with high tacrolimus variability in kidney transplant recipients (KTRs) is not well-studied. METHODS: Single-center, retrospective cohort study of adult KTRs converted from Tac immediate release to LCP-Tac 1-2 years post-transplant. Primary measures were Tac variability, using the coefficient of variation (CV) and time in therapeutic range (TTR), as well as clinical outcomes (rejection, infections, graft loss, death). RESULTS: A total of 193 KTRs included with a follow-up of 3.2 ± .7 years and 1.3 ± .3 years since LCP-Tac conversion. Mean age was 52 ± 13 years; 70% were African American, 39% were female, 16% living donor and 12% donor after cardiac death (DCD). In the overall cohort, tac CV was 29.5% before conversion, which increased to 33.4% after LCP-Tac (p = .008). In those with Tac CV >30% (n = 86), conversion to LCP-Tac reduced variability (40.6% vs. 35.5%; p = .019) and for those with Tac CV >30% and nonadherence or med errors (n = 16), LCP-Tac conversion substantially reduced Tac CV (43.4% vs. 29.9%; p = .026). TTR significantly improved for those with Tac CV >30% with (52.4% vs. 82.8%; p = .027) or without nonadherence or med errors (64.8% vs. 73.2%; p = .005). CMV, BK, and overall infections were significantly higher prior to LCP-Tac conversion. In the overall cohort, 3% had rejection before conversion and 2% after (p = NS). At end of follow-up, graft and patient survival were 94% and 96%, respectively. CONCLUSIONS: In those with high Tac CV, conversion to LCP-Tac is associated with a significant reduction in variability and improvement in TTR, particularly in those with nonadherence or medication errors.

Diabetes is a significant and independent predictor for tacrolimus immediate release and LCP-tacrolimus conversion ratios.

Diabetes (DM) is a common comorbidity in transplant patients with known effects on gastrointestinal (GI) motility and absorption; however, DM's impact on immediate release (IR) tacrolimus to LCP-tacrolimus (LCP) conversion ratios has not been studied. This multivariable analysis of a retrospective longitudinal cohort study included kidney transplant recipients converted from IR to LCP between 2019 and 2020. The primary outcome was IR to LCP conversion ratio based on DM status. Other outcomes included tacrolimus variability, rejection, graft loss, and death. Of the 292 patients included, 172 patients had DM and 120 did not. The IR:LCP conversion ratio was significantly higher with DM (67.5% ± 21.1% no DM vs. 79.8% ± 28.7% in DM; P < .001). In multivariable modeling, DM was the only variable significantly and independently associated with IR:LCP conversion ratios. No difference was observed in rejection rates. Graft (97.5% no DM vs. 92.4% in DM; P = .062) and patient survival (100% no DM vs. 94.8% in DM; P = .011) were lower with DM. The presence of DM significantly increased the IR:LCP conversion ratio by 13%-14%, compared to patients without DM. On multivariable analysis, DM was the only significant predictor of conversion ratios, potentially related to GI motility or absorption differences.

A Critical Analysis of the Specific Pharmacist Interventions and Risk Assessments During the 12-Month TRANSAFE Rx Randomized Controlled Trial.

BACKGROUND: Medication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss. OBJECTIVE: To describe the frequency and types of interventions made during a pharmacist-led, mobile health-based intervention in KTX recipients and the impact on patient risk levels. METHODS: This was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels. RESULTS: A total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients. CONCLUSION AND RELEVANCE: A pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.

Challenges for expansion of thoracic transplant clinical pharmacy in a developing country: comparison with U.S. accredited centres and call for action.

WHAT IS KNOWN AND OBJECTIVE: Clinical pharmacists' involvement in the care of solid organ transplant recipients has been discussed worldwide given its potential to improve clinical outcomes. As thoracic transplant activity grows in Brazil, it is important to understand how pharmacists are inserted in transplant programmes nationwide. We conducted a survey to explore clinical pharmacy activities in thoracic transplant centres in Brazil and compared them with accredited programmes in the United States. METHODS: An electronic questionnaire was distributed to all 40 heart and lung transplant centres registered in the Brazilian Organ Transplantation Agency (ABTO) in May 2019. Survey findings were compared to previously published data from accredited U.S. centres. RESULTS AND DISCUSSION: From 22 centre respondents, ten (45.5%) declared not to have a pharmacist at any part of the transplantation process, which translated into 158 (37.6%) transplant recipients without any direct pharmaceutical care. In centres with pharmacists (n = 12), none had a full-time professional dedicated to their heart and/or lung programmes. When compared to U.S. centres, there was a significantly lower insertion of clinical pharmacist activities among Brazilian centres. WHAT IS NEW AND CONCLUSION: Our findings point to an unmet need related to clinical pharmacy activity within thoracic transplant programmes, especially in a developing country, and highlight a call for action in order to reach higher accredited regulatory standards regarding pharmacist-driven workforce in transplant care worldwide.

Significant hospitalization cost savings to the payer with a pharmacist-led mobile health intervention to improve medication safety in kidney transplant recipients.

This was an economic analysis of a 12-month, parallel arm, randomized controlled trial in adult kidney recipients 6 to 36 months posttransplant (NCT03247322). All participants received usual posttransplant care, while the intervention arm received supplemental clinical pharmacist-led medication therapy monitoring and management, via a smartphone-enabled mHealth app, integrated with risk-based televisits. Hospitalization charges were captured from the study institution accounts payable and non-study institution hospitalization charges were estimated using multiple imputation. Multivariable modeling was used to assess the impact of the intervention on charges. The intervention significantly reduced rates of hospitalization (1.08 per patient-year in the control arm vs 0.65 per patient-year in the intervention arm, p = .007). The control arm had estimated hospitalization costs of $870,468 vs $390,489 in the intervention arm. Modeling demonstrated a 49% lower hospitalization charge risk in the intervention arm (RR 0.51, 95% CI 0.28-0.91; p = .022). From a payer or societal perspective, the net estimated cost savings, after accounting for intervention delivery costs, was $368,839, with a return on investment (ROI) of $4.30 for every $1 spent. These results demonstrate that a mHealth-enabled, pharmacist-led intervention significantly reduced hospitalization costs for payers over a 12-month period and has a positive ROI.

Etiologies and Outcomes Associated With Tacrolimus Levels Out of a Typical Range That Lead to High Variability in Kidney Transplant Recipients.

BACKGROUND: High tacrolimus intrapatient variability (tac IPV) is associated with poor outcomes in kidney transplantation, including rejection, donor-specific antibodies, and graft loss. A common cause of high tac IPV is related to patient nonadherence, but this is yet to be conclusively demonstrated. METHODS: This was a longitudinal cohort study comprising adult kidney recipients, who received transplants between 2015 and 2017, with follow-ups through February 2020. The goal of this study was to identify the most common etiologies of tac levels outside the typical range, which lead to high tac IPV, and assess the etiology-specific associations between high tac IPV and graft outcomes. Multivariate Cox regression was used to assess time-to-event analyses. RESULTS: In total, 537 adult kidney recipients were included; 145 (27%) were identified as having a high tac IPV (>40%) 3-102 months post-transplant. Common etiologies of tac levels significantly outside the standard goal range (6-12 ng/mL) leading to high tac IPV included patient nonadherence (20%), infections (19%), tac-related toxicities (17%), and undocumented issues (27%). In multivariable Cox modeling, those with high tac IPV because of nonadherence had a 3.5 times higher risk of late acute rejection (P = 0.019) and 2.2 times higher risk of late graft loss (P = 0.044). No other etiologies in the typical tac level range were significantly associated with either acute rejection or graft loss. CONCLUSIONS: Although high tac IPV has many causes, only high tac IPV caused by nonadherence is consistently associated with poor allograft outcomes.

A comprehensive review of the impact of tacrolimus intrapatient variability on clinical outcomes in kidney transplantation.

Tacrolimus (Tac) is widely used to prevent rejection and graft loss in solid organ transplantation. A limiting characteristic of Tac is the high intra and interpatient variability associated with its use. Routine therapeutic drug monitoring (TDM) is necessary to facilitate Tac management and to avoid undesirable clinical outcomes. However, whole blood trough concentrations commonly utilized in TDM are not strong predictors of the detrimental clinical outcomes of interest. Recently, researchers have focused on Tac intrapatient variability (Tac IPV) as a novel marker to better assess patient risk. Higher Tac IPV has been associated with a number of mechanisms leading to shortened graft survival. Medication nonadherence (MNA) is considered to be the primary determinant of high Tac IPV and perhaps the most modifiable risk factor. An understanding of the methodology behind Tac IPV is imperative to its recognition as an important prognostic measure and integration into clinical practice. Therapeutic interventions targeting MNA and reducing Tac IPV are crucial to improving long-term graft survival.

Phenotype of immunosuppression reduction after kidney transplantation.

BACKGROUND: Immunosuppressive regimens are delivered without direct measure of the net state of immunosuppression. Besides therapeutic drug monitoring, adjustments in immunosuppressive medications are largely event-driven. METHODS: We studied the clinical phenotype of immunosuppression reduction (ISR) among kidney transplant recipients from 2005 to 2012. Patients were grouped into: no ISR, ISR for infection, or ISR for intolerance. Outcome measures were rejection, rejection-free survival, and IFTA-free survival. RESULTS: 1114 adult kidney transplant recipients were included: 57% had no ISR, 16% had ISR for infection, and 27% had ISR for intolerance. ISR for infection was mainly on MMF, while ISR for intolerance was mainly on FK. ISR was associated with higher rates of acute rejection. The Kaplan-Meier analysis showed increased prevalence of rejection among patients with ISR due to infection (P = .003) or intolerance (P = .05). The risk of interstitial fibrosis and tubular atrophy was increased in patients with ISR due to infection (P = .001) or intolerance (P = .018). CONCLUSION: Immunosuppression reduction is associated with increased prevalence of rejection. The clinical phenotype of ISR is dominated by IFTA remote from the onset of ISR. Solely focusing on acute rejection may underestimate effects of ISR on long-term graft function and survival.

Patterns of emergency department utilization between transplant and non-transplant centers and impact on clinical outcomes in kidney recipients.

There is a high rate of Emergency Department (ED) utilization in kidney recipients post-transplant; ED visits are associated with readmission rates and lower survival rates. However, utilization within and outside transplant centers may lead to different outcomes. The objective was to analyze ED utilization patterns at transplant and non-transplant centers as well as common etiologies of ED visits and correlation with hospitalization, graft, and patient outcomes. This was a longitudinal, retrospective, single-center cohort study in kidney transplant recipients evaluating ED utilization. Comparator groups were determined by ED location, time from transplant, and disposition/readmission from ED visit. 1,106 kidney recipients were included in the study. ED utilization dropped at the transplant center after the 1st year (P < .001), while remaining at a similar rate at non-transplant centers (0.22 vs 1.06 VPPY). Infection and allograft complications were the most common causes of ED visits. In multivariable Cox modeling, an ED visit due to allograft complication at a non-transplant center >1 year post-transplant was associated with higher risk for graft loss and death (aHR 2.93 and aHR 1.75, P < .0001). The results of this study demonstrate an increased risk of graft loss among patients who utilize non-transplant center emergency departments. Improved communication and coordination between transplant centers and non-transplant centers may contribute to better long-term outcomes.

Impact of a multidisciplinary multimodal opioid minimization initiative in kidney transplant recipients.

Opioid use after kidney transplant has been shown to be a risk factor for chronic opioid use, which leads to an increased risk of mortality. The purpose of this study was to evaluate the early impact of a multimodal pain regimen and education quality improvement program on opioid use after kidney transplant 2 months after implementation. This was a retrospective, single-center analysis of post-operative opioid use, comparing the average daily Morphine milligram equivalents (MME) of the patients who received education on opioids and a multimodal pain regimen (preoperative TAP/QL block, scheduled APAP and gabapentin) compared to a historical control group. Despite having no differences in pre-transplant opioid exposure, daily and overall inpatient opioid utilization was significantly reduced in the multimodal pain protocol cohort (38.6 vs 8.0 MME/day; P < .001); 5% of patients in the multimodal pain protocol cohort were discharged with an opioid prescription, compared to 96% of controls (P < .001). Our early results demonstrate that a multimodal pain protocol can effectively and dramatically reduce short-term opioid utilization in kidney transplant recipients.