PURPOSE OF REVIEW:Vascularized composite allotransplantation (VCA) restores form and function after disfiguring tissue loss with the required need for lifelong immunosuppression for a non-life-saving indication, creating a distinct risk-benefit ratio compared to other solid organ transplants. This review summarizes recent advances in VCA immunosuppression, with emphasis on strategies that reduce drug-related toxicity while preserving graft function. RECENT FINDINGS:Long-term cohort data continue to document substantial nephrotoxic, metabolic, infectious, and oncologic morbidity from tacrolimus-based triple therapy, with measurable decline in renal function within the first posttransplant year and tacrolimus exposure as the strongest correlate. Costimulation blockade has produced preclinical and early clinical efficacy, particularly belatacept combined with antithymocyte globulin induction to avoid the need for long-term use of calcineurin inhibitors. Next-generation anti-CD40 agents are positioned to overcome the thromboembolic toxicity that limited earlier anti-CD154 antibodies. Regulatory T-cell therapy and chimerism-based tolerance remain promising and investigational. SUMMARY:Tacrolimus-based triple therapy remains the clinical standard, with its concomitant nephrotoxicity requiring kidney transplantation after face and hand transplantation in some cases. Costimulation blockade-based, calcineurin inhibitor-sparing protocols represent an advanced path toward safer VCA immunosuppression.
PURPOSE OF REVIEW:Recent work has linked gut dysbiosis, an imbalance of commensal and pathogenic bacteria, to complications in kidney transplant recipients. The purpose of this review is to evaluate the gut microbiota's relationship to important complications in kidney transplantation. RECENT FINDINGS:In both allogeneic hematopoietic stem cell transplant and solid organ transplant recipients, gut dysbiosis has been linked to an increased risk of infections and higher mortality rates. In kidney transplant recipients, elevated intestinal uropathogen abundance is associated with development of urinary tract infection, and an imbalance between commensal and pathogenic bacteria has been linked to posttransplant diarrhea. SUMMARY:Gut dysbiosis with elevated abundance of pathogenic bacteria and decreased abundance of commensal bacteria is associated with urinary tract infections and posttransplant diarrhea in kidney transplantation.
PURPOSE OF REVIEW:The purpose of this review is to discuss common pain phenotypes in transplantation, summarize known gut microbiome features associated with chronic pain, and to map known gut microbiome features in transplantation with diagnosis-independent pain features. RECENT FINDINGS:Persistent pain is common across solid organ and hematopoietic stem cell transplantation, arises from diverse mechanisms, and often extends well beyond the perioperative period. Growing evidence supports the gut microbiome as a biologically plausible modulator of chronic pain across disease states, including transplantation. Alterations in microbial diversity, microbial metabolites, intestinal barrier integrity, and neuroimmune signaling have been linked to pain amplification and central sensitization across multiple chronic pain conditions. In transplant populations, exposure to immunosuppressive therapies, antibiotics, metabolic comorbidities, and other transplant-related stressors creates a unique environment for sustained microbiome disruption that may contribute to persistent symptom burden. SUMMARY:Collectively, these data highlight the importance to systematically assess and manage pain as a core transplant outcome rather than a secondary concern, and to highlight the potential role of the gut microbiome as a risk screening tool or a therapeutic target for pain interventions. Although mechanistic and observational data support biologic plausibility, transplant-specific microbiome-pain evidence remains preliminary and warrants longitudinal investigation.
PURPOSE OF REVIEW:Corticosteroids, calcineurin inhibitors, antimetabolites, and mammalian target of rapamycin (mTOR) inhibitors have formed the basis of immunosuppression in clinical solid organ transplantation for decades. This review aims to outline recent advances in precision-based immunosuppression for solid organ transplantation. RECENT FINDINGS:Co-stimulation blockade has been explored as both tolerogenic and maintenance immunosuppression over the last two decades, resulting in the application of belatacept in clinical settings. Dual co-stimulation blockade is the latest in this area of study. Recent updates in monoclonal antibody-based immunotherapy have resulted in widespread off-label clinical implementation of eculizumab and alemtuzumab with new drugs still in phase II/II trials. Additional strategies, including autologous regulatory T cell (Treg) and chimeric antigen receptor-Treg cell (CAR-Treg) based therapies, are at the forefront of therapeutic immunomodulation. Early data have demonstrated safety and feasibility with ongoing phase II studies in these cell-based therapies, aiming to verify efficacy in early and long-term graft survival. SUMMARY:The past decade has seen advancement in costimulatory blockade, as well as immune modulatory therapy with monoclonal antibodies. Cellular therapies such as CAR-Tregs remain in the early clinical trial phase.
PURPOSE OF REVIEW:Transplantation of the intestine is a vital component in the treatment of many intrabdominal tumors. This is a comprehensive review of current practice and outcome of intestinal transplantation for tumors. RECENT FINDINGS:Most commonly described for the intrabdominal desmoid tumor, excellent survival outcomes can be attained, particularly for the more aggressive desmoid tumors associated with familial adenomatous polyposis syndrome and early referral is critical in order to avoid diffuse tumor spread which would necessitate a more complex multivisceral transplant. Currently, consensus within the intestinal transplant community lists invasive intrabdominal desmoid tumor as a primary indication for intestinal transplantation. Rare tumors such as metastatic neuroendocrine tumors confined to the abdomen, and pseudomyxoma peritonei have been associated with acceptable survival and recurrence outcomes with intestinal transplantation in carefully selected patients who would otherwise have a dismal prognosis. In addition, intestinal transplantation is an option for patients with a history of abdominal malignancy who have been rendered with intestinal failure due to surgical complications from resection of a primary tumor. SUMMARY:Intestinal transplantation is a therapeutic option with excellent results in selected patients with intrabdominal desmoid tumors, neuroendocrine tumors and pseudomyxoma peritonei. Careful patient selection, technical expertise, and posttransplant oncologic surveillance is critical for successful long-term outcomes.
PURPOSE OF REVIEW:Short bowel syndrome intestinal failure (SBS-IF) occupies a unique position at the interface between chronic organ failure management and intestinal transplantation (iTx). Historically, patients with SBF-IF progressed inevitably toward lifelong home parenteral support (HPS) dependence and, in a small and highly selected subset with impending HPS failure, ultimately to iTx. Recent advances in pro-adaptive pharmacological strategies, focusing on glucagon-like peptide (GLP)-2 and GLP-1-based approaches as adjuncts to conventional antimotility and antisecretory therapies, are reviewed, with implications for decision-making across the SBS-IF disease trajectory presented. RECENT FINDINGS:SBS-IF is now recognized as a dynamic and modifiable form of organ failure. Targeted pro-adaptive interventions reduce HPS dependence and improve patient-centered outcomes. Conventional antimotility and antisecretory therapies remain foundational, whereas GLP-2 analogues are the first pathophysiology-targeted, pro-adaptive therapies in SBS-IF, while GLP-1 receptor agonists have emerged as promising adjuncts in selected patients, particularly those with high-output phenotypes. SUMMARY:Multidisciplinary intestinal failure rehabilitation and gut-directed pharmacotherapy have altered the natural history of SBS-IF. Medical rehabilitation has shifted iTx from a default end-stage therapy to a targeted rescue option reserved for irreversible HPS failure, to be considered after optimized rehabilitation but before the transplant window is lost.
PURPOSE OF REVIEW:Calcineurin inhibitors (CNIs) and steroids remain the major components of immunosuppressive regimens despite long-term side effects including nephrotoxicity and derangements in metabolic parameters. Belatacept, the first costimulatory blockade molecule approved for prophylaxis of kidney transplant rejection, has been shown to improve renal function over long-term use compared with CNIs, though concerns regarding increased rates of acute rejection has limited its widespread use. This update describes the initial development of belatacept and costimulation blockade; reviews the current state of its use as a clinically applicable immunosuppressant; and discusses the future direction of costimulation blockade and its use with newly emerging immunosuppressive strategies. RECENT FINDINGS:Iterative refinements to belatacept-containing protocols have reduced the incidence of acute rejection to rates comparable to those seen in CNI-based regimens, while preserving both a glomerular filtration rate advantage as well as improvements in long-term patient and graft survival. Increasingly sophisticated mechanistic understanding of immunology has allowed belatacept to be combined with newly developed, targeted therapies to expand its use. Transplant of organs other than kidney have begun to use belatacept with encouraging results. SUMMARY:Belatacept offers significant advantages in kidney transplantation, minimizing the negative effects of steroids and CNIs. New combinations with standard and emerging medications, along with new indications and clinical applications, continues to widen its use and allow increasing access.
PURPOSE OF REVIEW:The Banff Human Organ Transplant (B-HOT) panel was developed to enable standardized targeted transcriptomic assessment of formalin-fixed paraffin-embedded (FFPE) transplant biopsies across centers and organs. As literature has now moved beyond proof-of-principle studies, it is time to examine whether B-HOT is ready for routine clinical use and in what context. RECENT FINDINGS:The literature is dominated by retrospective studies using archival FFPE kidney transplant biopsies. Data support use of B-HOT for diagnostic refinement of antibody-mediated (AMR) rejection, especially in biopsies with incomplete, borderline, or threshold-limited phenotypes. Studies also suggest value for prognostic enrichment and clarification of diagnostically challenging Banff phenotypes. Cross-organ applications in heart and uterus transplantation, as well as exploratory mechanistic studies in placenta-associated rejection biology, and xenotransplantation, support the panel's translatability. Emerging implementation-oriented studies include sparse classifiers, multiclass models, and automated reporting frameworks. SUMMARY:The strongest readiness evidence is for adjunctive use in kidney rejection classification, particularly AMR and threshold-limited or incomplete phenotypes. However, broader routine implementation remains limited by challenges related to threshold harmonization, cross-platform standardization, and per-biopsy heterogeneity. Prospective clinical utility studies are needed to determine whether B-HOT-guided management improves treatment decisions and graft outcomes.
PURPOSE OF REVIEW:The role of surveillance (protocol) biopsies in kidney transplantation remains controversial. Historically used to detect subclinical rejection before functional decline occurs, their utility must now be reassessed in the context of modern immunosuppression, evolving donor and recipient profiles, expanding therapies for recurrent kidney disease, and the emergence of noninvasive biomarkers. This review examines the effectiveness and cost-effectiveness of surveillance biopsies and proposes a pragmatic framework for their clinical use. RECENT FINDINGS:The prevalence of subclinical rejection has declined substantially in the modern immunosuppression era, particularly among recipients without donor-specific antibodies. Most lesions detected on surveillance biopsies now represent borderline or mild T-cell-mediated rejection or mild microvascular inflammation and the benefit of treating these findings remains uncertain. At the same time, surveillance biopsies continue to provide important diagnostic information, including early evidence of chronic injury, donor-derived disease, and recurrent primary kidney diseases. Decision-analytic models indicate that the cost-effectiveness of screening strategies depends heavily on recipient age, immunologic risk, and the likelihood that detected pathology will meaningfully alter management. Emerging non-invasive biomarkers offer promising adjuncts, but they cannot fully replace histological evaluation. SUMMARY:Routine surveillance biopsies for all kidney transplant recipients are unlikely to represent the most efficient monitoring strategy. A risk-stratified approach integrating immunologic risk, clinical context, dynamic changes in immunosuppression, and selective use of biomarkers may optimize detection of clinically meaningful injury while minimizing unnecessary procedures and healthcare costs.
PURPOSE OF REVIEW:Children undergoing liver transplantation are highly vulnerable to infections. Cholangitis is a potential post-transplant complication requiring broad-spectrum anti-infective therapy, raising concerns about antimicrobial resistance in this immunosuppressed population. We conducted a systematic review to evaluate antimicrobial management of post-transplant cholangitis in pediatric patients. RECENT FINDINGS:Nine heterogeneous studies were included. Definitions of cholangitis varied widely, combining clinical, laboratory, imaging, and microbiological criteria, highlighting the need for standardization. Gram-negative bacteria predominated, particularly Klebsiella spp., Pseudomonas aeruginosa , and Escherichia coli . Prophylaxis commonly relied on broad-spectrum antibiotics, and initial treatment was empirical in all studies, with occasional adjustment based on microbiological results. First-line therapies included piperacillin-tazobactam and third-generation cephalosporins. Second-line regimens involved agents from various antibiotic classes, including glycopeptides, lipopeptides, aminoglycosides, and fluoroquinolones, as well as antifungals. Meropenem was used as either first-line or second-line therapy. SUMMARY:Improved characterization and standardized reporting of pathogens and treatments are needed to guide targeted antimicrobial strategies and limit multidrug-resistant organisms. More detailed and harmonized data reporting is essential to optimize management of post-transplant cholangitis in children.
PURPOSE OF REVIEW:Living-donor kidney transplantation offers the highest survival benefit for patients with kidney failure, yet access remains limited by immunologic, biologic, geographic and logistical barriers. This review summarized recent developments in kidney-paired donation (KPD), highlights current challenges and outlines future directions to optimize program performance and equity. RECENT FINDINGS:KPD has expanded rapidly in the Unites States and globally, with multicenter national and transnational programs demonstrating excellent allograft and patient outcomes. Increasing the use of altruistic donors, advanced donation models and molecular HLA-matching algorithms have improved match rates and compatibility. Despite these advances, significant challenges persist, including overrepresentation of blood group O and highly sensitized candidates, uneven program participation, financial and logistical barriers, and the need for robust ethical frameworks. SUMMARY:Creating a national KPD program that is accessible to all transplant programs and incorporates compatible recipient-donor pairs would significantly improve the opportunities for living-donor kidney transplantation.
Purpose of review To summarize important papers published in the pediatric heart transplantation in the last year. Recent findings While advances have been made for pediatric patients who need heart transplantation, considerable challenges remain. Donor availability remains a key challenge, and work to both increase the number of donors and the quality of donor organs is ongoing. The field of pediatric heart transplantation benefits from registries such as the Pediatric Heart Transplant Society (PHTS) and learning networks such as the Advanced Cardiac Therapies Improving Outcomes Network (ACTION), allowing for multisite collaboration to optimize survival both before and after transplant, and to share learning about complex cases. Psychosocial evaluations of potential recipients and families can be challenging, and a consensus framework is now available for these evaluations, to provide appropriate oversight and management of a scarce resource. Looking ahead, heart transplant specialists are anticipating advances in xenotransplantation, which has the potential to revolutionize current standards of care. Summary Donor availability and organ scarcity are the dominant challenges we face, with many recent impactful papers addressing this issue either directly or indirectly. It will be critical to maintain the forward progress made in addressing these challenges, while readying the field for big changes to come.
PURPOSE OF REVIEW:Behavioral and mental health challenges are important to understand in order to ensure that patients receive the anticipated benefits from organ transplantation. The present review centers on what we believe are the most important (and best researched) actionable challenges that may inform the care of transplant recipients - adherence to medical recommendations, transitions of care, and posttraumatic stress following transplantation. RECENT FINDINGS:Recent research has moved from identifying (and quantifying) the problem and is now trying to investigate how to best recognize - and address - behavioral and mental health challenges in this population. SUMMARY:While much remains unknown, it is increasingly becoming clear that early recognition is best done by increasing awareness amongst transplant team members, and objective surveillance methods. Subjective patient and parent reports should be considered if other methods are not available. It is becoming increasingly clear that psychosocial interventions are feasible and potentially effective. Transplant programs should try to be aware of such interventions, implement them when feasible, and create referral pathways that can be used when needed.
PURPOSE OF REVIEW:Living donor kidney transplantation (LDKT) provides superior outcomes compared to deceased donor kidney transplantation (DDKT), yet significant disparities persist in access and utilization across demographic groups in the United States. This review synthesizes current evidence on racial, socioeconomic, and geographic barriers affecting LDKT access. RECENT FINDINGS:Racial disparities remain substantial; white patients are most likely to receive LDKT, while black and Hispanic populations face lower referral, evaluation, and donation rates. Socioeconomic status further compounds disparities, with higher income and privately insured candidates enjoying greater LDKT access. Financial burdens for donors, including lost wages and donation expenses, are insufficiently offset by policies to date. Geographic variation in LDKT mirrors differences in access to transplant centers, with disadvantaged neighborhoods and low-volume centers contributing to reduced LDKT rates. Center-level practices, state policies, and distance to care all play critical roles. SUMMARY:As disparities in LDKT persist or worsen, achieving equity requires coordinated intervention across patient, provider, institutional, and policy levels, centered on dismantling structural barriers and meeting the goals established by national transplant initiatives. Addressing these factors is essential for ensuring just and equitable access to LDKT for all patients.
PURPOSE OF REVIEW:This manuscript highlights key areas of recent pediatric nephrology research that may be relevant to clinical practice. RECENT FINDINGS:Recent reviews of registry data have emphasized the long-term harms of even limited dialysis exposure in children, while studies of 'nonideal' donor kidneys in children have shown positive outcomes. New observational research suggests a benefit to thromboprophylaxis and aggressive fluid management immediately posttransplant, though the best prescriptions remain unclear. Belatacept and letermovir are emerging options for immunosuppression and CMV prophylaxis, respectively, that may have fewer side effects compared to standard of care; interventional studies of these drugs are ongoing. CONCLUSION:Transplant teams should consider using a broader range of donor organs in select pediatric patients. Further interventional research on peritransplant thromboprophylaxis and fluid management is needed to optimize management strategies. The completion of ongoing belatacept and letermovir trials have the potential to substantially alter posttransplant standards of care.
PURPOSE OF REVIEW:Normothermic machine perfusion (NMP) has emerged as technology for organ preservation and assessment. While NMP has been widely adopted for liver, lung, and heart transplantation, kidney NMP has faced slower clinical integration. Normothermic perfusion may potentially improve kidney transplant through improved preservation, graft viability assessment, mitigation of ischemia reperfusion injury, and treatment prior to transplant. The purpose of this review is to highlight the applications of NMP in kidney transplantation. RECENT FINDINGS:Kidney NMP has been proven well tolerated and feasible in multiple studies. Two recent randomized controlled trials did not demonstrate a benefit of NMP compared to cold storage. The use of NMP may increase utilization through improved logistics. Graft assessment during perfusion may allow for well tolerated transplantation of marginal kidneys. Successful long-term perfusion up to 4 days of discarded kidneys has been performed. Gene therapies and treatments, including immune modification, have been carried out during kidney NMP. SUMMARY:Normothermic perfusion has several applications to kidney transplantation including preservation, assessment, and treatment. Perfusion protocols viability criteria need to be defined. A portable, commercially available device is needed to increase clinical use. Further studies are needed to compare NMP to current preservation methods.
PURPOSE OF REVIEW:Highly sensitized kidney transplant candidates, particularly those with calculated panel reactive antibody (CPRA) ≥99.9%, face significant immunologic barriers to transplantation. This review highlights recent clinical strategies that have improved transplant access and outcomes in this population, with a focus on allocation policy, kidney-paired donation, and desensitization. RECENT FINDINGS:Updates from national allocation systems and kidney-paired donation programs have demonstrated substantial gains in transplant access for many highly sensitized candidates. However, those with CPRA at least 99.9% remain difficult to match. Novel desensitization approaches, such as imlifidase, proteasome inhibitors, anti-CD38 mAbs, and early-phase CAR T-cell therapies have shown promise in selected patients. Increasingly, immunologic phenotyping or gene expression profiling may help tailor desensitization strategies to individual recipients. SUMMARY:Most highly sensitized candidates now achieve transplant through allocation policy or paired donation. For those with CPRA at least 99.9%, desensitization will likely remain an important tool to facilitate transplantation. Emerging therapies and immunologic profiling may help individualize treatment and expand transplant access for this challenging group.
PURPOSE OF REVIEW:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading reason for liver transplantation (LT) worldwide. With limited donor availability and rising posttransplant morbidity due to chronic noncommunicable disease, preventive strategies are urgently needed. This review highlights the role of physical activity in MASLD before and after LT. RECENT FINDINGS:Epidemiologic and interventional studies show that regular physical activity reduces liver fat, improves insulin sensitivity, and lowers aminotransferases, even without significant weight loss, in individuals with noncirrhotic MASLD. Physical activity also enhances muscle strength, physical performance, and quality of life. Although most research has focused on earlier disease stages, physical activity remains feasible and beneficial for patients with advanced chronic liver disease (advCLD) due to MASLD, improving performance, reducing frailty, and maintaining transplant candidacy. Following LT, preliminary studies suggest that regular physical activity may reduce cardiometabolic complications and improve functional recovery, though data on preventing recurrent MASLD or improving long-term outcomes is inconclusive. SUMMARY:Physical activity should be integrated into clinical pathways before and after LT for individuals living with MASLD. Future studies should address the unmet needs in both the advCLD and post-LT populations where maintaining LT candidacy and optimizing survival, quality of life, and long-term outcomes remains of high public health significance.
PURPOSE OF REVIEW:Nearly half of all patients listed for kidney transplant now have obesity, which is associated with increased rates of perioperative complications and graft loss. Here, we provide an update on the management of obesity in patients with end-stage kidney disease (ESKD). RECENT FINDINGS:Lifestyle interventions are the backbone of obesity therapy but may be challenging to implement in transplant candidates due to dietary and activity limitations associated with ESKD and hemodialysis. Antiobesity medications (AOMs) acting on the glucagon-like peptide-1 receptor can result in weight loss up to 22% of total body weight, but evidence in ESKD is limited and their long-term use is limited by a high burden of gastrointestinal side effects and inconsistent insurance coverage. In terms of metabolic and bariatric surgery (MBS), the procedure of choice in transplant candidates is sleeve gastrectomy, which can result in weight loss up to 23% at 1 year and is associated with a lower risk of malabsorption and late complications, and possibly improved mortality compared to Roux-en-Y gastric bypass. SUMMARY:Lifestyle interventions, AOMs, and MBS are important options for transplant candidates with obesity, but more evidence is needed to define optimal treatment pathways involving AOMs and MBS in this population.
