Transplantation最新文献

Genetic testing is increasingly transitioning from being a research tool to standard clinical practice, but guidance for integrating genomics into living kidney donor assessment remains limited. This review provides an evidence-based framework for genetic testing in prospective kidney donors within clinical practice in Australia. Kidney donor genetic assessment requires first establishing a genetic diagnosis in the transplant recipient. Identifying which patients with chronic kidney disease warrant genetic testing depends on clinical phenotype, extrarenal manifestations, age of onset, and, crucially, family history of kidney disease. When a pathogenic variant is identified in the recipient, cascade testing of potential related donors enables informed decision-making, although interpretation requires nuance beyond simple positive or negative results. Genetic results should complement rather than replace traditional phenotypic donor assessment, with recognition that negative results do not eliminate all genetic risk. We propose a clinical algorithm for genetic assessment in potential living kidney donors in this review. For donor-recipient pairs with uncertain risk, we recommend shared decision-making within specialized kidney genetics clinics. Key principles of genetic testing include comprehensive genetic counseling, multidisciplinary team involvement, cascade testing strategies, and equitable access. These frameworks aim to optimize donor safety while maintaining access to living kidney transplantation for recipients with genetic kidney disease.

Background: Ureterostenosis affects 1%-8.3% of kidney transplant recipients, causing graft hydronephrosis, dysfunction, and potential loss. Traditional surgical repairs are invasive, technically challenging, and have a high recurrence risk. Magnetic compression anastomosis (MCA) presents a novel, minimally invasive alternative.

Methods: A systematic case series was conducted of 14 transplant recipients with ureterostenosis who were treated with MCA between January 2018 and January 2023. All patients underwent initial percutaneous nephrostomy decompression. Under ureteroscopic guidance, a daughter magnet was advanced antegrade via the percutaneous nephrostomy tract to the stricture. A parent magnet was positioned retrograde cystoscopically. Magnets were aligned under visual guidance for compression.

Results: MCA was technically successful in all 14 patients; the mean operative time was 89.9 ± 17.1 min, and blood loss was minimal. Magnets detached spontaneously in 13 patients (mean 15.4 ± 2.5 d). One patient with prior failed open revision required endoscopic magnet removal at 72 d. Postrecanalization, 2 F6 double-J stents were placed for 3-6 mo. The follow-up time was >2 y. One patient (7.1%) developed recurrence after stent removal, managed successfully with restenting. Kidney function stabilized/improved in all. Five patients were diagnosed with urinary tract infections and were cured after anti-infective treatment.

Conclusions: MCA shows significant advantages over conventional treatments for ureterostenosis after kidney transplantation. It is technically feasible, minimally invasive, with short operative times, negligible blood loss, rapid recovery, high primary success, and excellent preservation of graft function. MCA emerges as a promising, reliable first-line option, especially for short-segment strictures.

Roux-en-Y (RY) and duct-to-duct (DD) anastomosis are 2 techniques for biliary reconstruction in orthotopic liver transplantation (OLT), but their effectiveness in patients with primary sclerosing cholangitis (PSC) remains debated. This meta-analysis compares outcomes of DD versus RY reconstruction in OLT for PSC. A systematic review identified studies comparing these surgical approaches. Primary outcomes were postoperative biliary complications, while secondary outcomes included graft and patient survival, cholangitis, cholangiocarcinoma, recurrent PSC, hepatic artery thrombosis, and need for retransplantation. Risk of bias was assessed using the Risk Of Bias In Nonrandomized Studies-of Interventions tool. Binary outcomes were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs), whereas patient and graft survival were evaluated by estimating hazard ratios (HRs) from reconstructed Kaplan-Meier data. Twelve studies with 1418 patients were included, 891 (62.8%) undergoing RY and 527 (37.2%) DD reconstruction. Biliary strictures (OR, 1.18; 95% CI, 0.71-1.97) and leaks (OR, 1.23; 95% CI, 0.68-2.20) did not differ significantly. DD reconstruction was associated with a lower risk of cholangitis (OR, 0.37; 95% CI, 0.15-0.91). Importantly, patient (HR, 0.69; 95% CI, 0.55-0.86) and graft (HR, 1.38; 95% CI, 1.12-1.69) survival were superior in the RY group. No significant differences were found in other secondary outcomes. DD reconstruction decreases the risk of cholangitis but is associated with worse patient and graft survival compared with RY in PSC patients undergoing OLT. RY anastomosis may represent the safer reconstructive strategy in this population.

Sex disparities have been identified in rates of referral for transplant evaluation, rates of activation on the waitlist, time to transplantation, candidate survival on the waitlist, and graft and patient survival after transplant. Healthcare providers may contribute to these disparities through unconscious or conscious bias in selection of patients for transplant evaluation, activation on the waiting list, or access to life-sustaining therapies as a bridge to transplant. Both biologic differences between males and females and gendered behaviors may also contribute to sex disparities in transplant access and outcomes. This review will provide an overview of our current understanding of the magnitude and direction of sex differences at each stage of the kidney, heart, liver, and lung transplant trajectory. Potential mechanisms underlying the observed sex differences will also be considered. The combined impacts of multiple, sometimes competing, factors-including the role of selection bias on subsequent outcomes-will also be explored. Existing evidence points to restricted access to transplant for females compared with males, particularly at older ages. Sex differences in graft loss and excess mortality rates vary by donor sex and recipient age. A comprehensive understanding of the magnitude and direction of sex differences in transplantation access and outcomes is only the first step in addressing disparities. Further research is needed to determine mechanisms. A commitment from transplant professionals to achieve equitable access and outcomes is also required.

Background: Mitochondrial dysfunction contributes to cardiac pathology and may influence myocardial recovery after heart transplantation (HTX). However, posttransplant mitochondrial function in human myocardial tissue remains poorly characterized. We hypothesized that myocardial mitochondrial function would recover in the early posttransplant period and that improvements would correlate with cardiac recovery and metabolic status.

Methods: In this prospective single-center study, 45 adult HTX recipients underwent serial endomyocardial biopsies from 1 week to 6 mo post-HTX. Mitochondrial function was assessed using high-resolution respirometry, evaluating complex I-mediated respiration, maximal oxidative phosphorylation, respiratory control ratio, and coupling control ratio. Correlations with echocardiographic, hemodynamic, and biochemical variables were evaluated.

Results: Mitochondrial function remained stable throughout follow-up, with no significant changes in complex I respiration, maximal oxidative phosphorylation, respiratory control ratio, or coupling control ratio. Echocardiography showed significant improvement in biventricular function, including a 15% increase in global longitudinal strain (P = 0.0003) and a 20% increase in tricuspid annular plane systolic excursion (P = 0.0004). At 6 mo, global longitudinal strain correlated with maximal oxidative phosphorylation (r = -0.552; P = 0.0005) and respiratory control ratio (r = -0.479; P = 0.0031). No associations were found with cardiac output, cardiac index, troponin I, or N-terminal pro-brain natriuretic peptide. Pretransplant glycated hemoglobin correlated inversely with maximal oxidative phosphorylation at 6 mo (r = -0.351; P = 0.0026).

Conclusions: Myocardial mitochondrial function remained stable during early posttransplant recovery. Its association with echocardiographic improvement and pretransplant glycemic state suggests a link between left ventricular contractility and mitochondrial function, and a potential influence of metabolism on myocardial energetics.