Post-transplant Management Research Articles

Prerenal Transplant Education and Evaluation Positively Impacts Outcomes.

Introduction: An outstanding question in kidney transplantation is how to prepare candidates and their social supports for optimal posttransplant outcomes. Project Aims: This program evaluation assessed whether a pretransplant quality improvement clinic improved clinical outcomes in the year posttransplant compared to recipients receiving standard of care. Design: The Countdown to Transplant Clinic was implemented with kidney transplant candidates expected to receive a transplant within the next few months. The clinic included an enhanced education session on posttransplant lifestyle management, confirmation of support (≥2 adults), and evaluations by transplant social work, psychology, and nephrology. Results: Seventy-five patients participated in the clinic and underwent a transplant. A retrospective chart review of posttransplant laboratory values, rehospitalizations (within 3-months posttransplant), biopsy-confirmed graft failure, and mortality (within 1-year posttransplant) were collected from both groups. Univariate and multivariate propensity score-weighted linear or logistic regression models were used to evaluate the association between clinic participation and outcomes. In models adjusting for relevant covariates, participation in The Countdown to Transplant Clinic (vs standard care) was associated with a lower coefficient of variation of serum tacrolimus (all values collected 3-12 months posttransplant), 30-day posttransplant white blood cell counts (but not 90-day), 90-day posttransplant potassium, and 30 and 31 to 90 days rehospitalizations. Clinic participation did not predict serum glucose levels at 30- or 90-days posttransplant. Due to low rates of rejection and mortality, meaningful comparisons were not possible. Conclusion: Participation in a pretransplant, multicomponent clinic may improve certain outcomes of interest posttransplantation. Pilot testing for feasibility for randomized controlled trials is a necessary next step.

Emerging biomarkers in kidney transplantation and challenge of clinical implementation.

Despite improvement in short-term outcomes after kidney transplantation, long-term outcomes remain suboptimal. Conventional biomarkers are limited in their ability to reliably identify early immunologic and nonimmunologic injury. Novel biomarkers are needed for noninvasive diagnosis of subclinical injury, prediction of response to treatment, and personalization of the care of kidney transplant recipients. Recent biotechnological advances have led to the discovery of promising molecular biomarker candidates. However, translating potential biomarkers from bench to clinic is challenging, and many potential biomarkers are abandoned prior to clinical implementation. Despite these challenges, several promising urine, blood, and tissue novel molecular biomarkers have emerged and are approaching incorporation into clinical practice. This article highlights the challenges in adopting biomarker-driven posttransplant management and reviews several promising emerging novel biomarkers that are approaching clinical implementation.

Abstract 11935: The Index of Microcirculatory Resistance to Predict Subsequent Acute Cellular Rejection and Cardiac Events After Heart Transplantation

Introduction: Single center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute cellular rejection. Hypothesis: To validate whether IMR measured early after transplantation can predict subsequent acute cellular rejection and long-term outcome in a large multicenter cohort. Methods: From 5 international heart transplantation cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was biopsy-proven acute cellular rejection of grade 2 or 3 within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE, the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission due to a cardiac cause) at 10 years. Results: IMR was measured at a median of 7 weeks (interquartile range: 3 to 10 weeks) post-transplantation. Patients with acute cellular rejection grade 2 or 3 at the time of IMR assessment were excluded. At 1 year, the incidence of acute cellular rejection was 14.0%. IMR was associated proportionally with the risk of acute cellular rejection (per increase of 1-unit IMR; adjusted hazard ratio [aHR], 1.04; 95% confidence interval [CI], 1.01-1.06; P=0.002). The incidence of acute cellular rejection in patients with IMR ≥ 18 was 23.8%, while the incidence of acute cellular rejection in those with IMR < 18 was 5.5% (aHR, 4.09; 95% CI, 1.67-10.0; P=0.002). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-unit IMR; aHR, 1.03; 95% CI, 1.01-1.05; P=0.002). Conclusions: IMR measured early after heart transplantation is associated with subsequent acute cellular rejection at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized post-transplantation management.

Robot-assisted kidney transplantation: an update

ABSTRACTRenal transplantation has become the gold-standard treatment for the majority of patients with established renal failure. Recent decades have seen significant progress in immunosuppressive therapies and advances in post-transplant management of recipients, resulting in improved graft and patient outcomes. However, the open technique of allograft implantation has stood the test of time, remaining largely unchanged. In a world where major advances in surgery have been facilitated by innovations in the fields of biotechnology and medical instrumentation, minimally invasive options have been introduced for the recipient undergoing kidney transplantation. In this review we present the evolution of minimally invasive kidney transplantation, with a specific focus on robot-assisted kidney transplant and the benefits it offers to specific patient groups. We also discuss the ethical concerns that must be addressed by transplant teams considering developing or referring to robotic programs.

Impact of a National Multicentric Strategy to Support Kidney Transplant Patients During the COVID-19 Pandemic in Latin America: FUTAC Team Creation and Activities.

Impact of a National Multicentric Strategy to Support Kidney Transplant Patients During the COVID-19 Pandemic in Latin America: FUTAC Team Creation and Activities.

The effect of exercise training interventions in adult kidney transplant recipients: a systematic review and meta-analysis of randomised control trials

Background Kidney transplant recipients (KTRs) are characterised by adverse changes in physical fitness and body composition. Post-transplant management involves being physically active, although evidence for the effect of exercise is limited. Objective To assess the effects of exercise training interventions in KTRs. Methods NCBI PubMed (MEDLINE) and CENTRAL (EMBASE, WHO ICTRP) databases were searched up to March 2021 to identify eligible randomized controlled trials (RCTs) that studied exercise training in adult KTRs. Outcomes included exercise capacity, strength, blood pressure, body composition, heart rate, markers of dyslipidaemia and renal function, and health-related quality of life (QoL). Results Sixteen RCTs, containing 827 KTRs, were included. The median intervention length was 14-weeks with participants exercising between 2–7x/week. Most studies used a mixture of aerobic and resistance exercise. Significant improvements were observed in cardiorespiratory function (VO2peak) (3.21 ml/kg/min, p = 0.003), 6MWT (76.3 meters, p = 0.009), physical function (STS-60, 4.8 repetitions, p = 0.04), and high-density lipoprotein (HDL) (0.13 mg/dL, p = 0.03). A moderate increase in maximum heart rate was seen (p = 0.06). A moderate reduction in creatinine was also observed (0.14 mg/dl, p = 0.05). Isolated studies reported improvements in strength, bone health, lean mass, and QoL. Overall, studies had high risk of bias suggestive of publication bias. Conclusions Exercise training may confer several benefits in adult KTRs, particularly by increasing cardiorespiratory function and exercise capacity, strength, HDL levels, maximum heart rate, and improving QoL. Additional long-term large sampled RCTs, incorporating complex interventions requiring both exercise and dietary behaviour change, are needed to fully understand the effects of exercise in KTRs.

Doppler ultrasonography is a useful tool for the diagnosis of hemodynamics in congestive graft injury due to heart failure after liver transplantation: A case report

IntroductionPatients with end-stage liver disease often have cardiac dysfunction, which can be worsened by hemodynamic instability in liver transplantation, causing congestive graft injury.Presentation of caseA 28-year-old male with Wilson's disease underwent liver transplantation. The patient's history included cirrhotic cardiomyopathy and a preoperative ejection fraction of 37% on echocardiography. After liver transplantation, massive transfusion and acute renal failure led to increased central venous pressure. Doppler ultrasonography (US) showed an increase in positive components of the hepatic vein triphasic wave, followed by pulsatile changes in the portal vein waveforms and an eventual to-and-fro pattern. Laboratory data showed severe elevations of hepatocellular transaminase levels. Based on Doppler US findings, we determined liver damage was due to passive congestion caused by heart failure. Immediate initiation of continuous hemodiafiltration (CHDF) and intra-aortic balloon pumping (IABP) led to the patient's recovery from severe heart failure and graft injury.DiscussionIn our case, changes in the hepatic and portal vein waveforms and marked elevation of hepatocellular transaminases implied exacerbation of heart failure caused by hepatic congestion and injury. Worsening heart failure, in turn, led to progressive liver damage as the result of hepatic passive congestion. The patient's condition was successfully managed with early initiation of CHDF and IABP.ConclusionDoppler US can help diagnose congestive graft injury due to heart failure in liver transplant patients and should be performed during post-transplant management of patients with cardiac dysfunction.

The management of post-transplantation recurrence of hepatocellular carcinoma.

The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.

Heart transplantation in the era of COVID-19 pandemic: delirium, post-transplant depression, and visitor restrictions; the role of liaison and inpatient psychosomatic treatment—a case report

BackgroundHeart transplant recipients show a high risk of developing major depression with an increased risk of post-transplant morbidity and mortality. Heart transplant specialists and patients face unprecedented challenges during the COVID-19 pandemic, which have enormous clinical implications such as the increased risk of COVID-19 as well as visitor restrictions with social isolation during the post-transplant inpatient treatment.Case summaryWe present a case of a 64-year-old woman with end-stage heart failure caused by non-compaction cardiomyopathy who received an orthotopic heart transplant (OHT) without any intra-operative complications. Post-operatively, she showed acute psychotic symptoms in the intensive care unit (ICU) with improvement after switching intravenous tacrolimus treatment to an oral intake. Furthermore, the patient developed severe depressive symptoms with malnutrition and had a prolonged hospitalization. Standard medical care was complemented by intensive psychocardiological treatment to overcome the crisis.ConclusionHigh complexity of the post-transplant management after OHT underlines the importance of multidisciplinary teamwork, involving heart transplant specialists and allied mental health professionals. This collaboration led to an excellent long-term result. Facing the COVID-19 pandemic, the hospital visitor policies may be scrutinized, carefully looking at the role of social isolation, post-operative experience in the ICU, and medical complications after OHT.

Lung transplantation for interstitial lung disease.

Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide. Several unique features in patients with ILD can impact optimal timing of referral or listing for LTx, pre- or post-transplant risks, candidacy and post-transplant management. As the epidemiology of LTx and community practices have evolved, recent literature describes outcomes and approaches in higher-risk candidates. In this review, we discuss the unique and important clinical findings, course, monitoring and management of patients with IPF and other progressive fibrotic ILDs during pre-LTx evaluation and up to the day of transplantation; the need for co-management with clinical experts in ILD and LTx is emphasised. Some post-LTx complications are unique in these patient cohorts, which require prompt detection and appropriate management by experts in multiple disciplines familiar with telomere biology disorders and infectious, haematological, oncological and cardiac complications to enhance the likelihood of improved outcomes and survival of LTx recipients with IPF and other ILDs.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-fourth pediatric lung transplantation report — 2021; Focus on recipient characteristics

In recent years, we have seen innovations in organ procurement and organ preservation, post-transplant management, and the use of non-transplant treatments for advanced heart and lung diseases. These developments continue to influence our decisions on recipient selection and transplantation. This focused report aims to document the changes that took place in the pediatric lung transplant recipient profile over the years and to identify important trends in recipient characteristics and their impact on post-transplant outcomes.

Risks and Benefits of Kidney Transplantation during the COVID-19 Pandemic: Transplant or Not Transplant?

COVID-19 has significantly affected the transplant community, by leading to decreased transplant activity and increased waiting list time. As expected, COVID-19 causes substantial mortality in both ESKD and kidney transplant populations. This is due to underlying CKD and a high prevalence of comorbid conditions, such as diabetes mellitus, hypertension, and cardiovascular disease in this group. Transplant programs have faced the difficult decision of weighing the risks and benefits of transplantation during the pandemic. On one hand, there is a risk of COVID-19 exposure leading to infection while patients are on maximum immunosuppression. Alternatively, there are risks of delaying transplantation, which will increase waitlist times and may lead to waitlist-associated morbidity and mortality. Cautious and thoughtful selection of both the recipient's and donor's post-transplant management has been required during the pandemic, to mitigate the risk of morbidity and mortality associated with COVID-19. In this review article, we aimed to discuss previous publications related to clinical outcomes of COVID-19 disease in kidney transplant recipients, patients with ESKD on dialysis, or on the transplant waiting list, and the precautions transplant centers should take in decision making for recipient and donor selection and immunosuppressive management during the pandemic. Nevertheless, transplantation in this milieu does seem to be the correct decision, with careful patient and donor selection and safeguard protocols for infection prevention. Each center should conduct risk assessment on the basis of the patient's age and medical comorbidities, waitlist time, degree of sensitization, cold ischemia time, status of vaccination, and severity of pandemic in their region.

Next-Generation Sequencing-Based Measurable Residual Disease (MRD) Monitoring Is Highly Predictive for Outcome after Allogeneic Stem Cell Transplantation

Background: Molecular predictors for relapse following allogeneic haematopoietic stem cell transplantation (alloHSCT) are urgently needed as 30-40% of AML patients experience recurrence of disease after HSCT. Measurable residual disease monitoring (MRD) for nucleophosmin 1 (NPM1 ) mutations has proven to be highly predictive for relapse in AML patients treated with or without alloHSCT. However, the majority of AML patients undergoing alloHSCT do not have the favorable NPM1 marker so that alternative markers and techniques are required. We studied a next-generation sequencing (NGS)-based error-corrected sequencing approach that is applicable to all mutations for its ability to prognosticate relapse and survival following alloHSCT.Aim: To evaluate the prognostic impact of MRD before alloHSCT in AML patients in morphologic complete remission (CR) using a novel approach of error-corrected sequencing applicable to the majority of AML patients.Patients and Methods: We studied 75 patients who underwent myeloablative (MA) (n=36) or reduced-intensity conditioned (RIC) (n=39) alloHSCT for AML in morphologic CR for the presence of MRD shortly before alloHSCT. All patients had at least one mutation in genes other than NPM1 or DNMT3A at the time of diagnosis that was identified by NGS with a myeloid panel on the Illumina platform. Amplicon-based error-corrected sequencing and bioinformatics was developed and applied to CR samples before alloHSCT analyzing 1-3 diagnostic mutations. Genomic DNA from peripheral blood (n=46) or bone marrow (n=29) was used for MRD assessment. Mutations in the following genes were used for MRD analysis in the indicated number of patients: IDH2 (n=12), FLT3 (n=10), RUNX1 (n=7), SF3B1 (n=6), NRAS (n=5), IDH1 and TP53 (n=4 each), KRAS and WT1 (n=3 each), CBL, ETV6, EZH2, STAG2 (n=2 each), BCOR, BCORL1, DDX41, PHF6, PTPN11, RAD21 , and SMC3 (n=1 each). 55 mutations were single nucleotide variants and 14 mutations were indels. The sensitivity of the assay was determined for each analysis and ranged from 10-4 to 10-5. Six patients (8%) had molecular persistence at high copy number in CR (variant allele frequency, VAF 31-51%) and were excluded from further analysis.Results: 31 of 69 patients (45%) were found MRD positive before alloHSCT with a median VAF of 0.19% (range 0.012% to 14.5%). Clinical and transplantation-associated characteristics were similarly distributed between MRD positive and negative patients. Cytogenetic risk according to MRC, ELN risk groups and molecular aberrations showed no significant differences between MRD positive and negative patients apart from more MRD positive patients being SF3B1 mutated. The median follow up was 6.1 years. 19 of 31 MRD positive patients (61%) and 7 of 38 MRD negative patients (18%) relapsed after alloHSCT. In MRD positive patients the MRD marker was also found in the majority of available relapse samples (9 of 11 patients, 82%). MRD negative patients who relapsed had lost the MRD marker in 4 of 5 available relapse samples (80%), suggesting high accuracy of our MRD assay. By competing risk analysis for cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) patients with positive MRD had a significantly higher CIR than MRD negative patients (P<.001; HR 4.85, 95% CI 1.95-12.1; 5 year CIR 67.7 vs 19%, Figure 1A), while NRM was not significantly different (P=.31; HR 0.44, 95% CI 0.09-2.14). Overall survival (OS) was significantly shorter in MRD positive compared to MRD negative patients (P=.029; HR 2.26, 95% CI 1.07-4.79; 5 year OS 38 vs 70%, Figure 1B). In multivariate analysis MRD status was an independent predictor of CIR (P<.001, HR 5.80, 95% CI 2.18-15.48) besides cytogenetic risk, and of OS (P=.013, HR 2.57, 95%CI 1.22-5.38) besides cytogenetic risk and WBC count.Conclusion: We provide evidence that NGS-based MRD monitoring can be applied to a large proportion of AML patients using almost any available molecular aberration. This approach requires morphologic confirmation of CR status in order to exclude patients with molecular persistence at high copy number, likely originating from preleukemic clones or germline mutations. NGS-based MRD is highly predictive of relapse and survival and may help refining transplant and posttransplant management in AML patients. [Display omitted] DisclosuresChaturvedi:Bayer Pharma AG, Berlin, Germany: Research Funding. Fiedler:Amgen, ARIAD/Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Patents & Royalties; Amgen, Pfizer: Research Funding; Amgen, Gilead, GSO, Teva, Jazz Pharmaceuticals: Other: Support for meeting attendance.

Post-transplant Management in Heart Transplant Recipients: New Drugs and Prophylactic Strategies

Post-transplant Management in Heart Transplant Recipients: New Drugs and Prophylactic Strategies

Tackling Chronic Kidney Transplant Rejection: Challenges and Promises.

Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants fails within ten years after transplantation. Both immunologic and non-immunologic factors contribute to late allograft loss. Chronic kidney transplant rejection (CKTR) is often clinically silent yet progressive allogeneic immune process that leads to cumulative graft injury, deterioration of graft function. Chronic active T cell mediated rejection (TCMR) and chronic active antibody-mediated rejection (ABMR) are classified as two principal subtypes of CKTR. While significant improvements have been made towards a better understanding of cellular and molecular mechanisms and diagnostic classifications of CKTR, lack of early detection, differential diagnosis and effective therapies continue to pose major challenges for long-term management. Recent development of high throughput cellular and molecular biotechnologies has allowed rapid development of new biomarkers associated with chronic renal injury, which not only provide insight into pathogenesis of chronic rejection but also allow for early detection. In parallel, several novel therapeutic strategies have emerged which may hold great promise for improvement of long-term graft and patient survival. With a brief overview of current understanding of pathogenesis, standard diagnosis and challenges in the context of CKTR, this mini-review aims to provide updates and insights into the latest development of promising novel biomarkers for diagnosis and novel therapeutic interventions to prevent and treat CKTR.

NAFLD: a multi-faceted morbid spectrum with uncertain diagnosis and complicated management.

Non-alcoholic steatohepatitis (NASH) can be considered the pandemic of these times, because of its global diffusion alongside obesity, diabetes, and metabolic dysfunction. It is a disease that often poses many difficulties, since making an early diagnosis is often impossible since specific diagnostic tests and criteria are missing: so, it needs a high degree of suspicion. Most of the times the evolution to its more severe and terminal step, NASH cirrhosis, is unavoidable and so are the social pressure on health system and economic consequences it brings back. The aim of this article is to provide a review of the literature about both non-alcoholic fatty liver disease (NAFLD) and NASH, thus structuring a wide, comprehensive, 360-degree work with a focus on all major aspects of NAFLD, spanning from diagnosis, physiopathology and its repercussions on liver transplantation. Moreover, we also focus on patients related issues both in pre- and post-transplant management (when these patients are listed for liver transplant). NAFLD and NASH are a contemporary plague, and an exhaustive knowledge of the problem throughout all its aspects is necessary in order to lower economic weight that metabolic issues bring back and to have an open view to possible solutions to all management issues that NASH patients have and that are often prohibitive to a definitive cure (for example cardiovascular risk in patients otherwise eligible to liver transplantation). We aim to offer a complete view on the actual knowledge about NAFLD and NASH, by an extensive review of the literature.

A Novel Post-Transplant Multimodal Antibody Management Protocol for Highly Sensitized Lung Transplant Recipients

<h3>Purpose</h3> In lung transplant candidates with a high-calculated panel reactive antibodies (cPRA), the waitlist time and risk of death are considerable. Additionally, the presence of post-transplant HLA antibodies is associated with chronic lung allograft dysfunction (CLAD) and mortality. Our center designed a post-transplant multimodal antibody management protocol (PMAMP) in an effort to alter immune response and minimize antibody development of highly sensitized recipients (cPRA > 80) with the goal of improving transplant outcomes. <h3>Methods</h3> This is a single center, retrospective evaluation of our PMAMP. Lung transplant recipients with cPRA >80% were eligible for our PMAMP (Table 1). From April 2019 to April 2020, there were 5 eligible patients who underwent transplant. For comparison, matched historical control data was collected from 7 highly sensitized patients who underwent transplant from March 2003 to September 2008 but did not receive PMAMP. Demographics and outcome data were collected. <h3>Results</h3> Demographics and outcomes are described in Table 2. To date, all 5 patients who underwent PMAMP are alive with CLAD-free survival and no episodes of rejection with a median transplant follow-up time of 427 days. Of note, all patients in both groups experienced at least one infectious complication following transplant. <h3>Conclusion</h3> Our PMAMP shows promise for mediating CLAD-free survival, rejection, and extending post-transplant survival in highly sensitized candidates undergoing lung transplant; however, more data and follow-up is needed to ensure the safety and efficacy of this protocol.

Satellite Strategy: A Simple Approach Which Solved Access to Lung Transplant in Uruguay

Purpose To show an organizational approach which solved access to lung transplantation. Methods In 2003 and through the ministries of health and national organ procurement organizations, Uruguay and Argentina, countries with geographical and cultural proximity, initiated a framework agreement in lung transplantation, a growing activity in Argentina not developed in Uruguay. In this agreement, the lung implant would be carried out in Argentina and the pre and post-transplant management and assistance on the waiting list in Uruguay. In order to provide quality care, a training program was started in world reference centers. The groundwork for the establishment of an Uruguayan procurement team was also started. This approach was simple but clever. In Uruguay, with 3.3 million inhabitants and no experience in the area of ​​lung transplantation, the organizational aspects and the training of human resources would have required a lot of time and financial resources. The number of transplants/year (Tx/y) would have been limited, which is strongly correlated with morbidity and mortality. Currently, with the incorporation of Uruguayan transplants, Fundacion Favaloro exceeds 30 Tx/y with improved results. Results Since 2003, more than 250 patients were evaluated and 93 listed. 42 transplants were performed, more than a half of them in the last 4 years. The underlying pulmonary diseases is similar to international registries, 3 were retransplantations. Nowadays, Uruguay has the higgest lung transplant rate of the region with 1,8 transplant/pmp each year, more than Argentina (0,98), Brasil (0,62) or Chile (0,83). Unfortunately waiting time remains excessively long (19.4 ± 17,6 months) and mortality on the waiting list is still high (30%). Taking into account the entire cohort of patients, adult and pediatric, uni- or bipulmonary, the median post-transplant conditional survival observed in Uruguay is 7.5 ± 2.5 years. 95% of transplant patients achieved total reintegration to work and/or educational tasks with a great positive impact on the quality of life measured using Likert scale. Conclusion This “satellite strategy” allowed the development of a lung transplantation program helping Uruguayan population to access this complex procedure, improving results for both countries. This organizational approach, based on solidarity and teamwork, could be transferred to other situations.

Primum non Nocere: Induction in Kidney Transplantation After Heart Transplantation.

Kidney allograft transplantation after heart transplantation remains a rare event with 70 reported in 2007 and this number declining to 30 subsequently and more recently rose to 60 per year. The fact that renal allograft transplantation is needed at all is due to the well-known nephrotoxicity of calcineurin inhibitors, the mainstay of contemporary immunosuppression in cardiac transplant recipients.1 End-stage renal failure has increased significantly in nonrenal transplant recipients from 1998 to 2007.2 The Registry of the International Society of Heart and Lung Transplantation has reported that by 5 y posttransplant, 4.1% of heart transplant recipients develop end-stage renal disease requiring renal replacement strategies such as dialysis or renal transplantation and these percentages double by 10 y posttransplant.3 As survival after cardiac transplantation improves and patients are living longer, the number of patients requiring renal transplantation will be increasing, explaining the increase mentioned above. That these numbers have not been increasing more rapidly is a result of more assiduous attention to posttransplant management with mitigation of renal dysfunction by reduction in calcineurin inhibitor (CNI) target trough levels. This is a consequence of the study by Ojo et al.1 However, given the improving, long-term survival after heart transplantation resulting in longer-term exposure to CNIs, there will be more patients needing renal transplantation. Therefore, the identification of optimal immunosuppressive regimens guaranteeing successful outcomes in heart transplant recipients receiving renal transplants after their heart transplants as a consequence of CNI toxicity is important. Pre–heart transplant congestion and decreased cardiac output can impair renal function as well. Thus, the study by Riad et al4 published in this edition of Transplantation is important and novel. The authors reviewed the Scientific Registry of Transplant Recipient data from the United States of heart transplant recipients who subsequently, at a later date as a result of end-stage renal disease, underwent kidney transplantation (N=617) and compared post–kidney transplant outcomes as a function of type of induction or absence of induction in the early posttransplant period: depletional induction (ie, antilymphocyte globulin or alemtuzumab) (N = 307, 49.8%), nondepletional (ie, anti-interleukin-2 receptor agents such as basiliximab) (N = 253, 41.0%), or no induction (steroids) (N = 57, 9.2%). They studied reasonable numbers of patients and found no differences in outcomes such as rejection rates or renal function, reflected by serum creatinine at 1 y post–kidney after heart transplant. There was also no difference in recipient or graft survival. One difference that was noted was an increase in rehospitalization for the depletional induction group (51.7%) and nondepletional induction group (50.7%) versus the noninduction group (39.1%). The difference in rehospitalization rates between the noninduction group and the 2 induction groups while numerically lower did not reach statistical significance, likely due in part to the small numbers of patients in the noninduction group. Because the depletional group included patients receiving alemtuzumab, which is associated with profound lymphopenia, one wonders whether this exacerbated rehospitalization in this group.5 Details regarding the causes of rehospitalization were unfortunately not provided by the authors, but the presumption is that these would include lymphopenia and infection though neither appeared to impact survival or graft function. A reduction in rehospitalization is of considerable importance to reduce exposure of immunosuppressed patients to infections. There is also the issue of cost. While this article does not do a detailed cost analysis, it is quite clear that use of both depletional and nondepletional agents is far more expensive than the noninduction alternative, corticosteroids. When one adds the cost of additional rehospitalizations, the differential cost between the 2 induction strategies and the noninduction strategy would be excessive and ideally prohibitive. The authors sum up the preferred approach in their article: “No induction may be the preferred choice due to a lack of benefits and costly rehospitalizations associated with induction agents.”4 This statement should be tempered by the relatively small number of patients in the noninduction group and the lack of statistical differences as a result. There may well be patient groups such as sensitized heart transplant patients who might benefit from induction in kidney transplantation after heart transplant. Ideally, a randomized clinical trial of induction strategies versus noninduction would provide the most definitive information, but given the small numbers of patients who have kidney transplants after heart transplantation annually, this might take a long time to accomplish. It is important to remember the dictum Primum non Nocere: first, do no harm (either medical or financial).

Opioid use practices of kidney transplant centers in the United States: A national survey of institutional practices

AbstractBackgroundThe opioid epidemic in the United States and the known risks of opioid utilization highlight the need for a better understanding of pain management around kidney transplantation. Although studies have been recently published describing efforts to minimize opioid therapy, clinical practices across the U.S. remain unknown.ObjectiveThe primary outcome of this study was to describe the programmatic use of opioids in the perioperative timeframe and upon discharge after kidney transplantation in the U.S.MethodsThis study was a cross‐sectional survey of transplant pharmacists to evaluate the national landscape of opioid management with regard to pretransplant candidacy, perioperative pain management, and posttransplant pain management. A 25‐question survey was distributed to members of transplant pharmacy listservs within the U.S. in March 2020.ResultsSixty‐three of 208 (30.3%) adult kidney transplant centers responded to the survey. The majority of institutions would actively list patients on an opioid (84.1%, 53/63) or medication for opioid use disorder (MOUD) (58.2%, 32/55). The majority of institutions (84%) utilized opioids for first‐line postoperative pain management in opioid‐naïve patients. More than half of the centers (55%) did not differentiate the postoperative pain regimen between opioid‐naïve and opioid‐experienced patients. A total of 72.6% of institutions prescribed opioids upon discharge from transplant, and 10.8% of the institutions prescribed subsequent opioid analgesics in the outpatient setting. Most (82.7%) of responders reported that their institutions did not have a written protocol or policy for posttransplant pain management.ConclusionThis survey highlights the existence of significant practice heterogeneity regarding opioid and MOUD utilization across kidney transplant programs in the U.S. Thus, transplant pharmacists have the opportunity within the context of their multidisciplinary team to develop multimodal pain management strategies to minimize opioid use while maintaining adequate pain control in kidney transplant candidates and recipients to continue to optimize patient care.