Beom Seok Kim

Although acute kidney injury (AKI) has been implicated as a potential adverse effect of statin therapy, experimental evidence supporting this association remains limited. Here, we investigated whether elevated levels of 25-hydroxycholesterol (25-HC), an oxysterol produced by activated macrophages and monocytes, increase susceptibility to statin-induced AKI. We found that atorvastatin and fluvastatin induced cell death in proximal tubular cells when combined with 25-HC. Consistently, administration of low-dose lipopolysaccharide triggered AKI in statin-treated mice. Mechanistically, impaired protein prenylation disrupted the autophagosome–lysosome pathway in proximal tubular cells. AKI was attenuated by mevalonate supplementation, which restored protein prenylation, and by macrophage/monocyte depletion, which reduced the cellular sources of 25-HC. Furthermore, combined exposure to fluvastatin and 25-HC increased kidney injury molecule-1 (KIM-1) expression in human induced pluripotent stem cell-derived kidney organoids. Together, these findings suggest that elevated macrophage-derived 25-HC under conditions of infection, inflammation, or major surgery may increase susceptibility to statin-induced AKI. Our study identifies a previously unrecognized interaction between statins and 25-HC and suggests potential strategies to mitigate kidney injury while preserving the therapeutic benefits of statins.

Peritoneal dialysis (PD) is performed at home, where contact with healthcare professionals between clinic visits is limited. This exploratory study examined how patients receiving PD and healthcare professionals traded off five predefined attributes of a mobile monitoring application, derived from the Korean PD home-care reimbursement framework (monthly price, regular consultation, unscheduled consultation, educational content, and data management), and estimated conditional willingness-to-pay (WTP) . Between March and May 2022, 130 patients and 32 healthcare professionals completed a forced-choice conjoint survey without an opt-out alternative. Within the experiment, price accounted for about one quarter of relative importance in both groups. Among the functional attributes, patients assigned the greatest importance to unscheduled (23.0%) and regular consultation (22.2%), whereas healthcare professionals assigned it to data management (22.4%). Both groups preferred nurse consultation over a 24-hour chatbot (part-worth utility 0.814 vs. 0.117 in patients; 0.901 vs. − 0.185 in professionals). Among healthcare professionals, perceived institutional WTP was highest for monitoring patients’ daily health records. These values were reported by individual clinicians, not institutional purchasers, and are conditional on the selected price range, an assumed linear price coefficient, and the forced-choice design. These exploratory findings describe stakeholder trade-offs within a predefined, reimbursement-based choice set and are hypothesis-generating.

Background: Time in target range (TTR) for blood pressure reflects the consistency of blood pressure control and may better predict outcomes than single measurements. We examined the association between systolic blood pressure (SBP)‐TTR and graft outcomes in kidney transplant recipients. Methods: We conducted a prospective observational cohort study including 4559 kidney transplant recipients from the nationwide KOTRY (Korean Organ Transplantation Registry; main cohort) and 828 from the multicenter KNOW‐KT (Korean Cohort Study for Outcome in Patients With Kidney Transplantation; replication cohort). SBP‐TTR within 110 to 130 mm Hg was calculated using linear interpolation of office blood pressure at 6, 12, and 24 months after transplantation (12, 24, and 36 months in the replication cohort). The primary outcome was a composite of death‐censored graft loss or ≥50% decline in estimated glomerular filtration rate. Results: Over a median follow‐up of 4 years, each 1‐SD increase in SBP‐TTR was associated with a 20% lower risk of the composite outcome (adjusted hazard ratio [aHR], 0.80 [95% CI, 0.71–0.91]). Compared with the 0% SBP‐TTR group, the 1% to 50%, 51% to 99%, and 100% SBP‐TTR groups had progressively lower risks (aHRs, 0.69 [95% CI, 0.50–0.95]; 0.63 [95% CI, 0.46–0.87]; and 0.47 [95% CI, 0.31–0.71], respectively). Stronger associations were observed among recipients of deceased donor kidneys and those with older or female donors or a higher baseline SBP. The replication cohort showed similar associations. All‐cause death was not significantly associated with SBP‐TTR after multivariable adjustment in either the main cohort (aHR per 1‐SD increase, 0.88 [95% CI, 0.71–1.09]) or the replication cohort. Conclusions: A higher proportion of time with SBP within the target range of 110 to 130 mm Hg was associated with a lower risk of graft dysfunction, with consistent effects across most subgroups and more pronounced benefits in high‐risk populations. These findings suggest that sustained SBP control within this range may be clinically relevant in kidney transplant recipients; however, randomized controlled trials are needed to confirm causality and inform therapeutic strategies.

A United States study proposed the concept of Time-to-Equivalent Risk (TiTER) as a decision-making tool for accepting organs from expanded-criteria donors. While this study demonstrated a higher initial cumulative incidence of deceased donor kidney transplantation (DDKT) than death, the applicability and pattern of TiTER may differ in regions with extreme organ scarcity, such as Korea. Using comprehensive, nationwide cohort data from the Korean Network for Organ Sharing registry and National Health Insurance (2008-2022), we analyzed the cumulative incidence and competing risks of DDKT versus waitlist mortality, estimating the Korean TiTER (K-TiTER). Analyses were stratified by recipient age, Korean Estimated Post-Transplant Survival (K-EPTS), blood type, and donor quality. Among 51,427 waitlisted patients, 10,603 (20.6%) received DDKT. The cumulative incidence of DDKT was initially lower than that of death, in the opposite pattern to the United States study. Therefore, K-TiTER was defined as the earliest time when DDKT probability exceeds waitlist mortality. Among candidates aged ≥65 years, those with high K-EPTS scores (75-100), or blood type O, K-TiTER was frequently not reached, as the waitlist mortality consistently exceeded transplant probability. Notably, sensitivity analyses showed that expanding donor acceptance criteria shortened the time to probability crossover. This finding reframes suboptimal donor organs as a strategic accelerator for mitigating waitlist mortality, especially in candidates with poor prognosis. This descriptive study proposed preliminary hypotheses for the K-TiTER framework, indicating its potential to guide the identification of vulnerable candidates and support tailored allocation strategies or enrollment in innovative clinical trials for high-risk candidates.

Background: In pig‐to‐nonhuman primate islet transplantation, reliable, sensitive biomarkers are needed to detect graft damage at an early stage before irreversible islet loss occurs. In our study, we investigated donor‐derived cell‐free DNA (dd‐cfDNA) as an early, noninvasive biomarker of graft injury by analyzing its correlation with porcine C‐peptide levels, complement activation markers, and donor‐specific antibodies (DSAs). Methods: Streptozotocin‐induced diabetic cynomolgus monkeys received 50 000–100 000 IEQ/kg of intraportal islets from quadruple‐knockout (QKO; GGTA1 , CMAH , B4GALNT2 , and A3GALT2 ) pigs. Cohort 1 received antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and anti‐inflammatory agents (i.e., anakinra, adalimumab, and tocilizumab), whereas Cohort 2 received the same regimen plus rituximab and crovalimab. Graft function and immune responses were assessed by measuring porcine C‐peptide levels, complement activation markers, histology, and dd‐cfDNA kinetics. Results: Cohort 1 showed transient porcine C‐peptide secretion with marked dd‐cfDNA elevation at 7 d postoperatively that coincided with complement activation (i.e., C5a and membrane attack complex (MAC)) and dense CD3 ⁺ T‐cell and CD68 ⁺ macrophage infiltration, which resulted in early graft loss. Cohort 2 maintained stable C‐peptide levels, lower dd‐cfDNA levels, and reduced complement activation with improved graft preservation. Moreover, dd‐cfDNA correlated negatively with C‐peptide and positively with C5a but not with MAC. In both cohorts, DSA levels remained unchanged. Conclusions: Our study revealed that dd‐cfDNA levels correlate with graft damage and C5a in QKO porcine islet xenografts, which corroborates dd‐cfDNA utility as an early biomarker for predicting instant blood‐mediated inflammatory reaction (IBMIR). These findings indicate that dd‐cfDNA may be able to detect early islet xenograft damage.

IgA nephropathy, the most common primary glomerulopathy worldwide, is a kidney disorder of B-cell origin characterized by mesangial accumulation of IgA-containing immune complexes. In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)-Fc fusion protein that inhibits two key immunoregulatory cytokines - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) - that are thought to be central to the pathophysiology of IgA nephropathy. In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients with IgA nephropathy in a 1:1 ratio to receive atacicept at a dose of 150 mg once weekly, administered subcutaneously by patients at home, or matching placebo. The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. Safety was also evaluated. A total of 203 patients were included in the prespecified interim analysis: 106 patients in the atacicept group and 97 in the placebo group. At week 36, the percentage reduction from baseline in the urinary protein-to-creatinine ratio was 45.7% in the atacicept group and 6.8% in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% confidence interval, 28.9 to 52.3; P<0.001). Adverse events were observed in 59.3% of the patients in the atacicept group and in 50.0% in the placebo group; most were mild or moderate in severity. In this prespecified interim analysis, treatment with atacicept resulted in a significantly greater reduction in proteinuria than placebo at week 36 in patients with IgA nephropathy. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).

Koh HB, et al. Yonsei Med J. 2026 Jan;67(1):17-26. https://doi.org/10.3349/ymj.2025.0065

The efficient allocation of donor kidneys to appropriate candidates is mandated in Korea, with a very long waiting time for deceased donor kidney transplantation (DDKT). This study evaluated the prognostic implications of organ matching using the Korean Kidney Donor Profile Index (K-KDPI) and Korean Estimated Post-Transplant Survival (K-EPTS). We analyzed 7,443 DDKT recipients between 2008 and 2022 using national databases: the Korean Network for Organ Sharing and the National Health Insurance Data Sharing Service. Patients were classified into classes 1 (low K-KDPI [<70] to low K-EPTS [<20] score), 2 (low K-KDPI to high K-EPTS [≥20]), 3 (high K-KDPI [≥70] to low K-EPTS), and 4 (high K-KDPI to high K-EPTS). Patient and graft survival rates were compared among the groups. Compared with class 1, classes 2 and 4 demonstrated a higher risk of graft failure (hazard ratio [HR], 1.94 and 3.04 for classes 2 and 4, respectively). For patient survival, classes 2 (HR, 2.77) and 4 (HR, 4.29) exhibited an increased risk compared with class 1, whereas class 3 (HR, 1.32) did not show significant differences. We developed a predictive model for the survival benefits of DDKT over dialysis based on the K-KDPI and K-EPTS scoring systems. To enhance efficient utilization, it is desirable to introduce longevity-matching that prioritizes the allocation of donor organs with low K-KDPI to recipients with low K-EPTS. A predictive model of the survival benefits of DDKT over dialysis could guide decisions regarding the acceptance of organ offers.

Background: Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to resolve inequity in DDKT opportunity, whether DDKT has comparable outcomes in this disadvantaged population requires further study. This study assessed these outcomes and developed a new allocation system that balances equity and utility.Methods: Patients from national and hospital cohorts from two centers in Korea were categorized as B1 to B4 (according to panel reactive antibody [PRA] positivity and ABO blood type) and A1 to A4 (based on the maximal PRA% and blood type), respectively. Competing risk and Cox regression analyses were performed to assess the effects of PRA and blood type on graft failure and mortality, respectively. Based on DDKT opportunities and posttransplant outcomes, a new scoring system for kidney allocation was developed.Results: The national and hospital cohorts included 3,311 and 819 patients, respectively, who underwent DDKT. Despite the disparities in DDKT opportunities, the graft failure rates and mortality did not differ among the different PRA and blood type groups. Furthermore, posttransplantation outcomes did not differ according to the categories with different DDKT opportunities. A new scoring system to provide additional points to disadvantaged populations was developed based on the hazard ratios for DDKT.Conclusion: A new allocation approach based on PRA and ABO blood types offers benefits to disadvantaged patients with fewer DDKT opportunities and could enhance equity without sacrificing utility in Korea, which has a long waiting time for DDKT.