Transplant Recipients Research Articles

Review of plasma exchange and rituximab for prevention of recurrent focal segmental glomerulosclerosis after a prior graft loss

BACKGROUND Focal segmental glomerulosclerosis (FSGS) often recurs after transplantation, leading to graft dysfunction and graft loss. Patients who have lost prior grafts due to recurrence are at particularly high risk of re-recurrence in subsequent grafts. Rituximab and plasma exchange have been used pre-emptively to prevent post-transplant recurrence. However, the efficacy of such preventative measures remains unclear. AIM To investigate the outcomes of preventative rituximab and plasma exchange for recurrent FSGS in transplant recipients after prior graft loss. METHODS We conducted a systematic review of 11 studies with 32 patients who had experienced prior graft loss due to post-transplant FSGS recurrence and were treated with either pre-emptive plasma exchange alone, rituximab alone, or a combination of both. RESULTS Overall, 47% of the 32 patients experienced recurrence despite prophylactic treatment. Re-recurrence was seen in 25% (1/4) with pre-emptive rituximab alone, and 45% recurrence (9/20) with plasma exchange alone. Re-recurrence was noted in 63% with the use of combined plasma exchange and rituximab. CONCLUSION There is a paucity of available evidence in the literature to draw clear conclusions on the benefits of pre-emptive measures to prevent FSGS re-recurrence. The small sample sizes and variations in protocols call for larger and controlled studies to serve this patient population at high risk of recurrence and graft loss.

Supervised vs home-based exercise program in kidney transplant recipients: A pilot pragmatic non-randomized study

BACKGROUND Although the benefits of exercise for kidney transplant recipients (KTRs) have been widely demonstrated, these patients experience several barriers in undertaking a structured exercise program in hospital and non-hospital facilities. AIM To compare the effects of a supervised moderate-intensity gym-based intervention with a home-based low-intensity walking program on exercise capacity in KTRs. METHODS KTRs were asked to choose between two six-month programs. The first group performed a low-intensity interval walking intervention at home-based exercise intervention (HBex). The second group performed a supervised training program at an adapted physical activity gym (Sgym), including aerobic and resistance training. The outcomes, collected at baseline and at the end of the programs, included the 6-minute walking test, the peak oxygen consumption (VO2peak) during a treadmill test, the 5-time sit-to-stand test, and blood pressure. RESULTS Seventeen patients agreed to participate and self-selected into the HBex (n = 9) and Sgym (n = 8) groups. Two patients in the Sgym group dropped out because of familial problems. At baseline, patients in the HBex group were significantly older and had lower walking distance, VO2peak, and lower limb strength. Primary outcome changes were significantly greater in the HBex group than in the Sgym group (52 ± 23 m vs 8 ± 34; P = 0.005). No other significant differences between groups were observed. Both groups improved most of the outcomes in the within-group comparisons, with significant variations in VO2 peak. CONCLUSION Six-month moderate-intensity supervised or low-intensity home-based training programs effectively improved exercise capacity in KTRs. Gym-based programs combine aerobic and resistance training; however, in-home walking may be proposed for frail KTRs.

Clinical use of donor-derived cell-free DNA in kidney transplantation

Traditional monitoring of kidney transplant recipients for allograft dysfunction caused by rejection involves serial checks of serum creatinine with biopsy of the renal allograft if dysfunction is suspected. This approach is labor-intensive, invasive and costly. In addition, because this approach relies on a rise in serum creatinine above historical baselines, injury to the allograft can be extensive before this rise occurs. In an effort to address this, donor-derived cell-free DNA (dd-cf DNA) is being used with increasing frequency in the clinical setting as a means of diagnosing a rejection of the renal allograft early in the course. This can potentially allow for early intervention to minimize not only injury, but the intensity of antirejection therapy needed and the avoidance of side effects. Here, we will review the available methodology for the determination and quantification of dd-cf DNA, the data supporting its use in clinical practice and the limitations of this technology.

Cardiac evaluation of renal transplant candidates with heart failure

Patients with advanced kidney disease are at elevated risk of developing heart failure and appropriate risk stratification is important to permit them to receive kidney transplantation. The American Heart Association and American College of Cardiology joint statement provides guidance on risk stratification for the major cause of heart failure for these patients in its recommendations for coronary heart disease. Herein we provide an overview of the available literature on risk stratification for nonischemic heart failure and functional heart disease states such as pulmonary hypertension. Many of these options for optimizing these patients before transplant include optimizing their volume status, often with more aggressive ultrafiltration. Kidney transplantation remains the treatment of choice for patients with advanced kidney disease and cardiac disease, the correction of the azotemic substances with kidney transplantation has been associated with improved survival than remaining on dialysis long-term. The findings in the studies reviewed here are expected to help clinicians refine current strategies for evaluating potential kidney transplant recipients.

Fearsome four- Fungal infections in renal transplant recipients

To study the clinical presentation, diagnostic methods, treatment and outcomes of Invasive Aspergillosis Cryptococcal infection, Mucormycosis and Histoplasmosis in renal transplant recipients. : We performed a retrospective analysis of renal transplant recipients with four major fungal infections from January 2000 until December 2022 at a tertiary care centre in Southern India. This study was approved by the institutional ethical committee. We have identified these cases from the electronic records of the microbiology department and renal transplant outpatient clinic. A total of 1970 patients underwent renal transplantation at this institute during study period. A total of 25 patients were diagnosed as having invasive Aspergillosis - 20 patients had pneumonia, three had right maxillary sinusitis, one each had left chronic suppurative otitis media, and skull base osteomyelitis). There were 20 patients with cryptococcal infection of which eight had disseminated infection, seven had meningitis, four had cutaneous cryptococcosis and one had pulmonary cryptococcosis. Mucormycosis was diagnosed in 14 patients, twelve of which had pulmonary mucormycosis, one had oculo-cerebral mucormycosis and one patient had acute invasive fungal maxillarysinusitis. Histoplasmosis was diagnosed in four patients, two of whom had disseminated histoplasmosis and two had cutaneous histoplasmosis. In this study, mortality was highest with mucormycosis (57%) followed by 33.3% with invasive Aspergillosis and 20% with Cryptococci infection. Currently, there is no standard serological test available for the routine identification of invasive fungal infections in patients. Initial cultures may yield negative results due to slow fungal growth and variations in colony appearance. Therefore, it is essential to pursue aggressive sampling methods when fungal infection is suspected. Invasive procedures such as bronchoscopic lavage and abscess aspiration play a crucial role in reaching a diagnosis. In summary, maintaining a high level of suspicion and employing thorough investigations in post-renal transplant recipients are vital for early diagnosis, prompt treatment initiation, prevention of disease spread, and reduction of mortality risk.

Robotic Hysterectomy in Renal Recipient Lady with Very Large Fibroid Uterus

With time, proficiency in minimally invasive surgeries has been increasing, especially with the advent of robotic surgery. In this study, we present the case of a renal transplant recipient with a large uterine fibroid. She underwent a robotic hysterectomy with a multidisciplinary peri-operative management, considering her immunocompromised status.

Proton Pump Inhibitors: Effects on Magnesium and Arterial Stiffness in Renal Transplant Recipients

Proton Pump Inhibitors: Effects on Magnesium and Arterial Stiffness in Renal Transplant Recipients

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA. A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%. Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P=0.94; median, 0.31% [IQR, 0.17%-0.71%]; P=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P<0.001; median, 0.25% [IQR, 0.15%-0.52%]; P<0.001). HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.

Prolonged SARS-CoV-2 shedding in a lung transplant recipient: time for flexibility in infection prevention?

Prolonged SARS-CoV-2 shedding in a lung transplant recipient: time for flexibility in infection prevention?

The trend of Epstein-Barr virus DNA loads and CD8+ T lymphocyte numbers can predict the prognosis of pediatric liver transplant recipients with PTLD

Abstract Objectives Epstein-Barr virus (EBV) can cause lymphoproliferative disorders (PTLD) in immunodeficiency individuals. The pathogenesis of EBV infection depends on its effective recognition and elimination. Our study investigated the effect of peripheral lymphocyte subsets (PLS) on the elimination of EBV. Methods A retrospective single-center study included 63 patients with 17 pediatric liver transplant recipients with EBV-induced PTLD (PTLD group) and 46 patients diagnosed with EBV-induced mononucleosis (IM group). Dynamic monitoring of PLS with EBV-DNA loads was performed. Results EBV-DNA replicated at a high level (5.2E3∼5.93E7 copies/mL in PBMC) before treatment in all patients in PTLD group. B lymphocytes were the main infected cells. After treatment with Rituximab, the EBV-DNA loads decreased below the lower limit of detection in 10 patients (PTLD-stable disease, PTLD-SD group), and the viral loads replicated at lower level in six patients (PTLD-partial response, PTLD-PR group). In the PTLD-SD group, the percentage of CD3+CD8+ T lymphocytes increased beyond the normal range with the ascending of EBV-DNA loads, then it decreased to the normal range accompanied by the clearance of EBV. In the PTLD-PR group, the CD3+CD8+ T lymphocytes kept in the normal range, while the EBV kept on replication. Conclusions The increased number of CD3+CD8+ T lymphocytes occurred in parallel with the decline in EBV-DNA loads, which is the most useful index in estimating the host capacity of immuno-surveillance against EBV.

Patch Testing in Solid Organ Transplant Recipients: Experience From a Tertiary Medical Center Over 13 Years (2010-2022).

Background: It is generally recommended that patients not be on immunosuppressive medications for patch testing, as these medications may suppress delayed-type hypersensitivity and lead to false negative results. There is a paucity of literature describing organ transplant recipients who underwent patch testing. Objective: The aim of this study is to examine patch testing results in solid organ transplant recipients over a 13-year period at our institution. Methods: We performed a retrospective analysis of patch test data from adult transplant recipients at our institution. Transplant patients who underwent patch testing were identified from a clinical patch test database, and a chart review was conducted. Results: Eighteen patients were included in the study. Patients had received kidney, liver, or heart transplants. Seven patients (38.9%) had at least one positive reaction. The highest reaction rates were seen with methylisothiazolinone (12.5%), methyldibromo glutaronitrile (12.5%), and benzalkonium chloride (10.0%). Limitations included small sample size, data from a tertiary referral center, and retrospective analysis. Conclusions: Liver and kidney transplant recipients displayed allergic reactions during patch testing. Patients may benefit from patch testing even if receiving immunosuppressive therapy, but some reactions may be falsely negative because of immunosuppression.

NPC-21: A Potential Game Changer in the Fight Against Cytomegalovirus Disease in Transplant Recipients.

NPC-21: A Potential Game Changer in the Fight Against Cytomegalovirus Disease in Transplant Recipients.

Gut Microbial Dysbiosis and Implications in Solid Organ Transplantation

The gut microbiome has been shown to play a significant role in solid organ transplantation, potentially influencing graft function and patient outcomes. Dysbiosis, characterized by reduced microbial diversity and an increase in pathogenic taxa, has been linked to higher incidences of allograft rejection, graft dysfunction, and post-transplant mortality. Several studies suggest that the gut microbiome might be able to serve as both a biomarker and a therapeutic target, potentially guiding personalized immunosuppressive therapies and other interventions to improve outcomes after solid organ transplantation. As summarized in this review, clinical studies have shown that specific microbial shifts correlate with adverse outcomes, including acute rejection and chronic allograft dysfunction. As research surrounding the relationship between the gut microbiome and solid organ transplant progresses, the integration of microbial analysis into clinical practice has the potential to revolutionize post-transplant care, offering new avenues to improve graft survival and patient quality of life. This review aims to provide a comprehensive overview of the relationship between gut microbial dysbiosis and transplantation outcomes, emphasizing the impact on kidney, liver, lung, and heart transplant recipients.

Insights From a 20-Year Follow-Up of the First Heart Transplant Recipient to Complete an Ironman Triathlon.

Insights From a 20-Year Follow-Up of the First Heart Transplant Recipient to Complete an Ironman Triathlon.

Real-World Comparison of Maribavir to Foscarnet for the Treatment of Cytomegalovirus in Solid Organ and Hematopoietic Stem Cell Transplant Recipients

Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection. This was a single-center retrospective study of clinical outcomes of patients who received MBV compared to a control group who received FOS for an episode of CMV infection. Each cohort consisted of 27 episodes of CMV infection. Twenty patients in the MBV cohort and from the FOS cohort cleared the infection, with five and three patients developing MBV or FOS resistance, respectively. There were no statistically significant differences in failure of therapy as evidenced by persistent DNAemia (p = 0.56) or development of antiviral resistance (p = 0.24). In conclusion, MBV was as effective as FOS for the treatment of R/R CMV infection and was better tolerated without increased risk of antiviral resistance.

Bridging the Gap: A Review of Pediatric to Adult Transition of Care in Liver Transplantation.

With improvements in long-term graft function and survival, an increasing population of pediatric liver transplant (LT) recipients now require adult care. A process to successfully transition young adults to adult LT centers is supported in the literature with discussions on the rationale for health care transition (HCT), barriers to transition, stakeholder perspectives, and transfer readiness (TR). Results of outcomes studies are difficult to generalize and there remains no standard of care for HCT in LT. Of concern is that the youth's increasing independence occurs during a period of developmental vulnerability, with a threat to graft function due to risk-taking behaviors, specifically nonadherence, that may lead to rejection, graft loss, and death. The purpose of this comprehensive literature review is to discuss current knowledge, practices, and outcomes of HCT for LT recipients with additional support from literature in solid organ transplant (SOT) and pediatric-onset chronic conditions literature. Recent position statements in LT and SOT express a greater awareness of the importance of HCT with broad agreement that reflects a similarity in approach in endorsing HCT as an essential process that should be initiated in early adolescence with TR as a primary determinant of transfer; however, standardization with consistent outcomes measurement is lacking. The literature supports transition as an esential component of care that should be initated in early adolescence with programs that address knowlege, skill-development, and advocacy. The engagement of all stakeholders in LT is essential to program development. There is increasing awareness among the multidisciplinary team of the importance and role of the adult provider in extending transitional care into the adult setting as executive functioning skills mature. Outcome measures need to be clearly defined and standardized. Regulatory agency involvement to validate and support the need for TOC programs is crucial and should promote outcomes research for best practice program standardization.

Biopsy-Proven T-Cell Mediated Rejection After Belatacept Rescue Conversion: A Multicenter Retrospective Study

After kidney transplantation, conversion to belatacept is a promising alternative in patients with poor graft function or intolerance to calcineurin inhibitors. The risk of acute rejection has not been well described under these conditions. Here we present a retrospective multicenter study investigating the occurrence of acute rejection after conversion in 901 patients (2011–2021). The incidence of cellular and humoral rejection was 5.2% and 0.9%, respectively. T-cell mediated rejection (TCMR) occurred after a median of 2.6 months after conversion. Out of 47 patients with TCMR, death-censored graft survival was 70.1%, 55.1% and 50.8% at 1 year, 3 years and 5 years post-rejection, respectively. Eight patients died after rejection, mainly from infectious diseases. We compared these 47 patients with a cohort of kidney transplant recipients who were converted to belatacept between 2011 and 2017 and did not develop rejection (n = 238). In multivariate analysis, shorter time between KT and conversion, and the absence of anti-thymocyte globulin induction after KT were associated with the occurrence of TCMR after belatacept conversion. The occurrence of rejection after conversion to belatacept appeared to be less frequent than with de novo use. Nevertheless, the risk of graft loss could be significant in patients with already low renal function.

Interaction between ischemia-reperfusion injury and intestinal microecology in organ transplantation and its therapeutic prospects

Organ transplantation is a vital intervention for end-stage organ failure; however, ischemia-reperfusion injury is a complication of transplantation, affecting the prognosis and survival of transplant recipients. As a complex ecosystem, recent research has highlighted the role of the intestinal microecology in transplantation, revealing its significant interplay with ischemia-reperfusion injury. This review explores the interaction between ischemia-reperfusion injury and intestinal microecology, with a special focus on how ischemia-reperfusion injury affects intestinal microecology and how these microecological changes contribute to complications after organ transplantation, such as infection and rejection. Based on a comprehensive analysis of current research advances, this study proposes potential strategies to improve transplant outcomes, offering guidance for future research and clinical practice.

Early Hospital Readmission After Pediatric Liver Transplant: A Retrospective Analysis of the Society of Pediatric Liver Transplantation (SPLIT) Database.

Incidence of and risk factors for early hospital readmission (EHR) are poorly defined in pediatric liver transplant recipients. Therefore, we evaluated EHR incidence and risk factors for pediatric liver recipients in a nationally representative sample. Using the Society of Pediatric Liver Transplantation database, we retrospectively analyzed 2808 pediatric liver-only recipients transplanted 2011-2022. Recipient-, donor-, and center-level characteristics were evaluated as possible risk factors for EHR within 30 days of hospital discharge using multivariable modified Poisson regression. Overall, 23% (N = 642) of pediatric recipients experienced EHR. Independent risk factors for EHR include diabetes (adjusted relative risk [aRR] 2.33, 95% CI: 1.41-3.86, p = 0.001), history of malignancy (aRR 1.59, 95% CI: 1.19-2.11, p = 0.002), and shorter length of transplant hospitalization. Recipients in the shortest length of stay quartile (median [IQR] 8 [7-9] days) had a ninefold increased risk for EHR compared with recipients in the longest length of stay quartile (34 [28-48] days) (aRR 8.86, 95% CI: 5.68-13.81, p < 0.001). Incidence of EHR did not vary by transplant center and was not associated with other characteristics of the donor (DCD vs. not DCD), recipient (age, race, sex, and diagnosis), procedure (whole vs. split liver, ischemic time), or transplant center. We found the 30-day readmission rate for pediatric liver transplant recipients was 23%. Shorter hospital stays were a major risk factor for EHR, highlighting that longer initial transplant hospital stays may be beneficial for predischarge optimization and coordination of their complex care.

Recurrent Outbreak of Carbapenem-Resistant IMP-1-Producing Pseudomonas aeruginosa in Kidney Transplant Recipients: The Impact of Prolonged Patient Colonization.

Infections by carbapenem-resistant Pseudomonas aeruginosa (CRPA) have been associated with high morbidity and mortality among solid organ recipients. To delineate the epidemiological and molecular characteristics of a recurrent outbreak of imipenem (IMP)-producing P. aeruginosa (CRPA) among kidney transplant (KT) recipient METHODS: We described a recurring CRPA outbreak in a KT ward, divided into two periods: before unit closure (Feb 2019-2020) and after reopening (Aug 2020-Dec 2023). Routine surveillance cultures (SCs) were performed using axillary-perineum-rectal swabs with immunochromatographic tests. A case-control study identified risk factors for CRPA acquisition. Pulsed-field gel electrophoresis and whole genome sequencing characterized the strains. After reopening, new cases arose from patients previously colonized, peaking 18 months later. A total of 67 KT recipients with CRPA-IMP-producing strains were identified. All except one sequenced strain belonged to the ST446 clone, differing by a maximum of 110 single nucleotide polymorphisms. Forty-five (67.2%) cases were identified through SC, with 45.7% showing intermittent SC positivity. Patients remained colonized for up to 623 days. Twenty-four (35.8%) patients had infections, with the most common site being the urinary tract. Identified risk factors included older age, deceased donor, re-transplantation, reoperation, carbapenem or quinolone use, lymphopenia, hospital stay >10 days, and the first 60 days post-KT. KT recipients can harbor CRPA for extended periods, and detecting CRPA-colonized patients is challenging. These characteristics highlight the patient as the major source and a critical point in outbreak control.