Introduction:Dose-adjusted tacrolimus exposure phenotype, expressed as the trough concentration-to-dose ratio (C0/Dose), may influence post-transplant outcomes, but supporting evidence remains limited. Methods:We evaluated the association between tacrolimus exposure phenotype and short- and long-term allograft and patient outcomes in a multicenter retrospective cohort study using clinical data warehouse records from five tertiary transplant centers in South Korea (2005-2020). Patients were classified into fast- or slow-dose-adjusted exposure phenotypes using trajectory clustering. Primary outcomes included 1-year endpoints (graft failure, biopsy-proven acute rejection, de novo donor-specific antibodies, severe infection, cardiovascular events, malignancy, and death). Secondary outcomes were assessed using the same endpoints for 2-6 years. Inverse probability of treatment weighting (IPTW) and weighted Cox proportional hazards models were used to adjust for confounders. Results:Among 5,965 recipients, 4,595 (77.0%) were classified as fast-exposure phenotype and 1,370 (23.0%) as slow-exposure phenotypes. Slow-exposure phenotypes received lower tacrolimus doses (time-weighted median 2.1 vs 4.6 mg/day, P < 0.001) but had higher trough levels (6.7 vs 6.1 ng/mL, P < 0.001), higher variability (27.8 vs 26.4%, P < 0.001), and greater time above the therapeutic range (19.7 vs 11.6%, P < 0.001). After IPTW, 1-year efficacy outcomes (biopsy-proven acute rejection, graft failure, and de novo donor-specific antibody development) did not differ significantly between groups. During years 2-6, slow-exposure phenotypes had higher risks of all-cause mortality (adjusted HR 1.616, 95% CI, 1.069-2.442), serious infection requiring hospitalization (adjusted HR 1.537, 95% CI, 1.166-2.026), and malignancy (adjusted HR 1.628, 95% CI, 1.077-2.460). Discussion:A slow tacrolimus exposure phenotype (high C0/Dose) may serve as a risk marker of cumulative overexposure, associated with increased late mortality, serious infection, and malignancy. Phenotype-informed longitudinal exposure monitoring may improve long-term risk stratification, although whether targeted dose adjustment improves outcomes requires prospective interventional studies.

BackgroundCirculating donor-specific antibodies (sDSA) are clinically important markers of alloimmune risk, but their presence or strength does not always correspond to concurrent antibody-mediated rejection (ABMR) in kidney transplantation. We investigated whether intragraft donor-specific antibodies (gDSA) detected in kidney biopsy eluates are associated with histologic findings in recipients with concurrent sDSA positivity.MethodsAll available frozen kidney biopsies in recipients with concurrent weak to moderate sDSA at Seoul National University Hospital between January 2020 and June 2024 were included. Sixty biopsy eluates from 60 patients were tested using a Luminex single antigen bead assay and analyzed according to biopsy findings.ResultsThe prevalence of gDSA differed significantly across histologic diagnoses (overall P = 3.3 × 10-4), with higher positivity in C4d-only lesions (100.0%), aABMR (90.9%) and aABMR+TCMR (83.3%), whereas lower frequencies were observed in caABMR (44.4%), no rejection (22.7%), and aTCMR (14.3%). The gDSA positive rate in aABMR was significantly higher than that in the no-rejection group (corrected P = 0.003; OR 34, 95% CI 3.5–334). The MFI sum of gDSA was significantly higher in aABMR, aABMR+TCMR, and C4d-only lesions (corrected P = 0.009, 0.035, and 0.007, respectively). In contrast, the sum of sDSA MFI did not differ significantly across the histologic groups.ConclusionsIn kidney transplant recipients with concurrent sDSA, the presence and intensity of gDSA varied according to biopsy-proven histologic findings, most prominently in aABMR and related lesions. These findings suggest that gDSA may provide additional tissue-level immunologic context for understanding histologic heterogeneity among kidney transplant recipients with circulating sDSA.

Background:South Korea first implemented kidney paired donation (KPD) to overcome ABO-incompatible living-donor kidney transplantation. Although utilization declined as desensitization matured, persistent desensitization failure and anatomic constraints have renewed interest in KPD within a regulated framework. We report a recent single-center experience. Methods:KPD exchanges were coordinated within an institutional registry under national supervision. We retrospectively reviewed six consecutive, simultaneous two-way exchanges (12 recipients) from 2022 to 2025. We assessed predefined desensitization failure or anticipated failure with the intended donor, compared immunologic compatibility between intended and exchange donors, and recorded perioperative desensitization, graft function, delayed graft function (DGF), and biopsy-proven acute rejection (BPAR). Results:Five of six exchanges were undertaken for immunologic reasons. All five met criteria for desensitization failure or anticipated failure to the intended donor, with positive crossmatch and high donor-specific antibody (DSA) burden. Reassignment to the exchange donor reduced risk, lowering maximum DSA mean fluorescence intensity (MFI) from 13,228 to 1,350 and total DSA MFI from 20,542 to 2,240, although selective desensitization was still required in some recipients with residual human leukocyte antigen or ABO incompatibility. The remaining exchange addressed an anatomic constraint (adult-pediatric size mismatch). At a median follow-up of 12.2 months (range, 0.9-42.1 months), no DGF or BPAR occurred; all grafts were functioning, and the median estimated glomerular filtration rate was 66.8 mL/min/1.73 m2 . Conclusion:KPD is a safe alternative when desensitization fails or is predicted to fail, including in highly sensitized and anatomically complex candidates. These findings support renewed implementation of KPD alongside selective desensitization in Korea.

Background: In clinically stable kidney transplant recipients with de novo donor-specific anti-HLA antibodies (dnDSA), only 30 ~ 40% exhibit biopsy-proven rejection, leading to a substantial number of unnecessary biopsies. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising noninvasive biomarker of allograft injury. Nevertheless, its clinical utility for guiding biopsy decisions in dnDSA-positive stable kidney transplant recipients remains uncertain. This prospective multicenter cross-sectional study evaluated whether dd-cfDNA offers incremental predictive value for subclinical rejection in dnDSA-positive recipients with stable graft function. Methods: A total of 123 adult kidney transplant recipients with stable renal function were enrolled, comprising 46 dnDSA-negative and 77 dnDSA-positive patients. All participants underwent both dd-cfDNA and dnDSA testing, along with protocol or indication biopsies. Recipients with ABO-incompatible or preformed DSA-positive transplants were excluded. The diagnostic performance of dnDSA alone versus dnDSA combined with dd-cfDNA for predicting biopsy-proven subclinical rejection was assessed using receiver operating characteristic curve analysis. Results: Median dd-cfDNA levels were higher in dnDSA-positive patients (1.2% [IQR: 0.4–1.8]) compared with dnDSA-negative patients (0.3% [IQR: 0.2–0.4]). Subclinical rejection was histologically confirmed in 37 patients. Among dnDSA-positive recipients, combining dd-cfDNA ≥ 1.0 with dnDSA markedly improved diagnostic accuracy (AUC: 0.81; 95% CI: 0.74–0.88) compared with dnDSA alone (AUC: 0.74; 95% CI: 0.68–0.82). This combined approach achieved a positive predictive value of 46.2% and a negative predictive value of 97.8%. Moreover, elevated Banff microvascular inflammation (MVI) scores showed a strong correlation with higher dd-cfDNA levels ( P < 0.001). Conclusions: In dnDSA-positive kidney transplant recipients with stable renal function, dd-cfDNA provides incremental diagnostic value for identifying subclinical rejection and reflects the degree of microvascular injury. The integration of dd-cfDNA with dnDSA may enable more targeted and judicious use of biopsies, thereby reducing procedural burden while maintaining diagnostic precision.

Importance:Smoking is the strongest modifiable risk factor for peripheral arterial disease (PAD), yet evidence on how postdiagnosis smoking behavior changes affect clinical outcomes remains limited. Objective:To evaluate the association among smoking cessation, reduction, and continuation after PAD diagnosis and subsequent cardiovascular and limb-specific outcomes. Design, Setting, and Participants:This nationwide, population-based, retrospective cohort study assessed adults 40 years or older newly diagnosed with PAD from January 1, 2011, to December 31, 2018, with follow-up through 2021, who reported active smoking before diagnosis and completed health examinations before and after diagnosis. Data were from the Korean National Health Insurance Service-National Health Information Database. Data analysis was conducted from December 2023 to November 2025. Exposures:Postdiagnosis smoking behavior, classified as quitters (complete cessation), reducers (≥20% decrease in daily cigarette consumption), or maintainers (<20% decrease or any increase in consumption [reference group]). Main Outcomes and Measures:Main outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, myocardial infarction, coronary revascularization, and ischemic stroke, and major adverse limb events (MALEs), including limb revascularization or major amputation. Inverse probability of treatment-weighted hazard ratios (HRs) were estimated using Cox proportional hazards regression models for MACCEs and Fine-Gray competing risk models for MALEs. Results:Among 189 545 active smokers with incident PAD (mean [SD] age, 54.2 [11.8] years; 167 659 [88.5%] male), 38 952 (20.6%) quit smoking, 38 709 (20.4%) reduced consumption, and 111 884 (59.0%) maintained smoking. Compared with maintainers, quitters had significantly lower risks of MACCEs (17.8 vs 20.2 per 1000 person-years; HR, 0.88; 95% CI, 0.84-0.91) and MALEs (1.4 vs 1.8 per 1000 person-years; HR, 0.83; 95% CI, 0.73-0.94). Reducers showed no significant difference in MACCEs (HR, 1.00; 95% CI, 0.96-1.04) or MALEs (HR, 0.92; 95% CI, 0.81-1.04). Dose-response analysis showed risk reduction only with near-complete cessation. Findings were consistent across subgroups, with the largest reductions observed for myocardial infarction. Conclusions and Relevance:In this cohort study of 189 545 active smokers with newly diagnosed PAD, complete smoking cessation was associated with lower risks of both cardiovascular and limb-specific adverse events, whereas partial smoking reduction showed no significant benefit. These findings support complete cessation as the primary therapeutic target in patients with PAD.

Background: The rapid increase of minimally invasive surgery and the shortened training period for surgical residents has resulted in limited opportunities to acquire proficiency in open surgical techniques, such as vascular anastomosis. However, vascular anastomosis remains an essential skill in every surgery for bleeding control. This study aimed to validate the effectiveness of surgical education model for vascular anastomosis and assess the impact on the comprehension, skill, and confidence of surgical residents in performing vascular anastomosis. Methods: A total of 21 surgical residents with first to third years of experience at Seoul National University Hospital participated in a 4-week vascular anastomosis training program. The program included an educational lecture and the performance of an end-to-side anastomosis on a procedural model, with evaluations being conducted using the Objective Structured Assessment of Technical Skills (OSATS) and the End-Product Rating Score (EPRS) in pretraining and posttraining surveys. Results: Significant improvement was observed in the OSATS score (from 9.22 +/- 2.4 in week 1 to 12.87 +/- 3.1 in week 4; P < 0.001) and the EPRS score (from 12.47 +/- 4.1 in week 1 to 17.57 +/- 2.2 in week 4; P < 0.001). Additionally, the surgical performance time significantly decreased from 20.99 +/- 4.6 min to 16.33 +/- 4.2 min (P 1/4 0.019) Conclusions: Simulator training of in vitro vascular anastomosis, when accompanied by expert-led instruction, can effectively enhance the surgical proficiency, confidence, and overall surgical outcomes of residents, as inferred from the observed improvements in OSATS and EPRS scores. The results suggest that integration of this training model into surgical curricula could be a promising strategy for enhancing vascular surgical training.

BACKGROUND:The number of organ transplants in South Korea has increased, with a notable rise in living donor transplants. Ensuring their long-term health and well-being is critical to address potential complications and maintain the success of the transplant programs. METHODS:A diverse advisory panel, including transplant experts and coordinators, was established to evaluate the follow-up care for living donors. The panel reviewed the results of a brief survey of donors regarding their donation experience, follow-up programs, guidelines, and policies from South Korea and other countries, aiming to identify best practices and recommend improvements. RESULTS:The study found that follow-up care for living donors in South Korea is inconsistent and lacks standardization. Significant variability exists in follow-up practices across different institutions, and comprehensive data on donor health pre- and post-donation are scarce. The need for continuous, systematic follow-up, encompassing both medical and psychological support, is emphasized to ensure donor well-being. CONCLUSION:Improving follow-up care for living donors is essential. Establishing a national registry and increasing donor advocacy teams are meaningful steps to enhance donor care, ensure long-term health, and maintain ethical standards in organ donation.

BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive technique used to control non-compressible torso hemorrhage. However, the optimal degree of partial occlusion that offers maximum therapeutic benefit remains unclear. This study aimed to identify the optimal partial inflation volume for REBOA. METHODS:In a swine model of hemorrhagic shock, nine healthy female pigs were randomly assigned to three groups based on balloon inflation volume: 30% (R30), 60% (R60), and 100% (R100) of the volume required to eliminate the contralateral femoral arterial waveform. Hemodynamic variables, fluid and vasopressor requirements, and biochemical markers were evaluated during balloon occlusion and resuscitation following 40% blood volume-controlled hemorrhage. RESULTS:The R30 group showed higher mean arterial pressure during resuscitation and required less fluid and norepinephrine than those of the R100 group. The mean heart rate significantly differed over time among the groups, with more gradual changes in the R30 group. Markers of ischemia-reperfusion injury (lactate, pH, blood urea nitrogen, and creatinine) similarly exhibited significant temporal differences. Post hoc analysis revealed significant pH differences between the groups. The plasma lactate and creatinine levels were significantly lower in the R30 group than those in the other two groups. CONCLUSION:In this swine hemorrhagic shock model, partial REBOA with 30% balloon inflation maintained hemodynamic stability while reducing metabolic derangement compared with higher ballon volumes of 60% and 100% inflation. A strategy involving partial inflation targeting approximately 30%, followed by monitoring the blood pressure trend while using a vasoconstrictor, if necessary, may have potential clinical utility.

BACKGROUND:Persistent hyperparathyroidism after kidney transplantation (KT) has been reported in up to 50% of adult recipients, but pediatric data remain limited. We evaluated the prevalence, skeletal manifestations, and risk factors for persistent hyperparathyroidism in children following KT. METHODS:In this retrospective cohort study, 107 pediatric KT recipients (58% male; median age 10.3 years) transplanted between 2004 and 2019 were analyzed. Persistent hyperparathyroidism was defined as a median parathyroid hormone (PTH) > 65 pg/mL between 3 and 12 months post-KT. Risk factors for persistent hyperparathyroidism, post KT clinical features, and treatment status were analyzed. RESULTS:Thirty-six patients (33.6%) had persistent hyperparathyroidism after KT. On univariable analysis, dialysis duration of 24 months or longer (p = 0.028) and pretransplant hyperphosphatemia (p = 0.026) were significantly associated with persistent hyperparathyroidism. The multivariable model identified pretransplant hyperphosphatemia as an independent predictor (OR 2.70, 95% CI 1.10-6.87; p = 0.030). There was no significant difference in height Z score change between patients with and without persistent hyperparathyroidism (p = 0.97). However, persistent hyperparathyroidism was associated with poorer graft survival (log-rank p = 0.049). Six patients received cinacalcet and one underwent subtotal parathyroidectomy for refractory hypercalcemia. CONCLUSIONS:Persistent hyperparathyroidism is relatively common in pediatric KT recipients, affecting one-third of patients by one-year post-transplant. Prolonged dialysis and pre-existing hyperphosphatemia before KT may be risk factors. These findings underscore the importance of optimizing chronic kidney disease-mineral bone disease management and routine PTH monitoring before and after transplant in children.

KEY POINTS:Impaired early graft function effects differ by donor type: living donors show increased rejection/graft failure and deceased donors show mortality risk. Despite high-risk incompatible transplants, living donor recipients have low impaired graft function rates (4.5% versus 24.7% in deceased donors). Slow graft function is a distinct phenotype requiring recognition beyond traditional delayed graft function classification, with donor-specific implications. BACKGROUND:With the rise of high-risk living donor kidney transplantation, the effect of early graft function (EGF) on transplant outcomes remains unclear. METHODS:In this retrospective multicenter study, we classified kidney transplantation recipients (KTRs) based on EGF and donor type. EGF within the first post-transplant week was classified as immediate graft function, slow graft function (SGF), or delayed graft function (DGF), with impaired EGF defined as SGF or DGF. The primary outcomes included biopsy-proven acute rejection (BPAR) within 1 year, death-censored graft failure (DCGF), and overall mortality. RESULTS:Among 3261 KTRs, 365 (11.2%) experienced impaired EGF, including 190 (5.8%) with SGF and 175 (5.4%) with DGF. In living donor KTRs, impaired EGF was significantly associated with an increased risk of 1-year BPAR (adjusted hazard ratio [aHR], 2.13; 95% confidence interval [CI], 1.33 to 3.39) and DCGF (aHR, 2.49; 95% CI, 1.29 to 4.82) but not mortality. Both SGF and DGF increased the risk of BPAR, while only DGF significantly elevated the risk of DCGF. In deceased donor KTRs, impaired EGF was associated with a higher risk of both DCGF (aHR, 2.18; 95% CI, 1.43 to 3.31) and mortality (aHR, 2.30; 95% CI, 1.52 to 3.49) with SGF and DGF demonstrating similar patterns. Notably, prolonged DGF (≥7 days) was linked to progressively worse outcomes. CONCLUSIONS:The effect of impaired EGF varies by donor type. In living donor KTRs, impaired EGF increased the risks of BPAR and DCGF, particularly in cases of DGF. In deceased donor KTRs, impaired EGF elevated the risks of DCGF and mortality but not BPAR, highlighting the need for tailored strategies to optimize EGF.

Background. Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far. Methods. We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans. Results. This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors. Conclusions. If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.