Background:Although blood pressure and lipid control are key in advanced chronic kidney disease (CKD), the optimal targets for systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) remain unclear because patients with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 were often excluded or underrepresented in prior trials. This study aims to compare the clinical outcomes of intensive versus standard control strategies for SBP and LDL-C in patients with advanced CKD. Methods:This multicenter, open-label, randomized controlled trial with a 2 × 2 factorial design is being conducted across 13 centers in Korea. Adults aged ≥19 years with eGFR ≥15 and <45 mL/min/1.73 m2 , SBP ≥130 mmHg, and LDL-C ≥100 mg/dL are eligible. Participants will be randomized according to intensive or standard targets for SBP (<120 mmHg vs. <140 mmHg) and LDL-C (<70 mg/dL vs. <100 mg/dL). The effects of blood pressure and lipid interventions will be evaluated independently, sharing the same primary endpoint: time to the first composite kidney outcome, including ≥40% sustained decline in eGFR, initiation of kidney replacement therapy, sustained eGFR <10 mL/min/1.73 m2 , or kidney death. Secondary endpoints will include eGFR slope and major adverse cardiovascular events. Participants will be followed up for 3 years, with an additional 3 years for the observational phase. Results:This report describes the rationale and design; trial results are pending. Conclusion:As the first randomized trial to determine whether intensive SBP and LDL-C lowering improve kidney outcomes in advanced CKD, this study could help define optimal targets and inform future guideline recommendations.

BACKGROUND:Advances in haemopoietic stem cell transplantation (HSCT) have improved long-term survival, but they have also led to late complications, such as nephropathy. However, the safety and feasibility of kidney transplantation (KT) in patients with HSCT-related end-stage kidney disease (ESKD) remain unclear. AIM:This study aimed to evaluate the feasibility and clinical outcomes of KT in patients with ESKD following HSCT. METHODS:This study retrospectively analysed eight patients with ESKD who underwent KT following HSCT for haematologic disorders, including aplastic anaemia (n = 5), acute myeloid leukaemia (n = 2) and chronic myeloid leukaemia (n = 1). RESULTS:The median time to progression to ESKD was 104 months after HSCT, with a median interval of 138 months between HSCT and KT. The causes of ESKD included diabetic nephropathy (n = 1), hypertensive nephropathy (n = 1), focal segmental glomerulosclerosis (n = 1), thrombotic microangiopathy (n = 1) and unknown aetiology (n = 4), with three diagnoses confirmed through kidney biopsy. Three patients received both HSCT and KT from the same donor, allowing them to completely discontinue immunosuppressive therapy. During a median follow-up of 55 months (range 2-143 months), there was only one case of acute T-cell-mediated rejection, and one patient died from sepsis due to a urinary tract infection. Notably, none of the patients experienced a recurrence of their original haematologic disease. CONCLUSION:Despite concerns regarding immunosuppression and the risk of infection in this high-risk population, both patient and graft outcomes were favourable. These findings suggest that KT is a feasible and effective treatment option for patients with ESKD following HSCT, particularly when managed with personalised strategies.

Background/Aims: Owing to aging-related factors, arteriovenous access (AV) is difficult to establish in older patients; central venous catheter (CVC) access is used instead. However, evidence on long-term outcomes of permanent vascular access types in the oldest-old adults (≥ 80 yr) is lacking. We aimed to compare mortality by vascular access type in older Korean patients undergoing hemodialysis.Methods: This nationwide retrospective cohort study included 79,286 adult patients who initiated maintenance hemodialysis between 2012 and 2021, identified from the Korean National Health Insurance Service database. Patients were categorized by permanent vascular access type (AV fistula [AVF], AV graft [AVG], or CVC). Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess mortality across vascular access types. Analyses were stratified by age group.Results: CVC access was associated with the highest mortality. Compared with AVF use, CVC use was associated with more than a threefold increase in mortality risk (aHR 3.54; 95% CI, 3.43–3.65). Though attenuated, the CVC use-associated mortality risk remained significantly elevated in octogenarians and nonagenarians (aHR 3.30; 95% CI, 3.14–3.47 and aHR 3.18; 95% CI, 2.65–3.82, respectively). Compared with AVG use, CVC use remained consistently associated with elevated mortality risk across age groups.Conclusions: CVC use as permanent access was associated with increased mortality, even among the oldest-old. Advanced age should be regarded as a clinical consideration rather than a definitive contraindication to AV access. Our findings support the need for individualized clinical decision-making, even in the oldest-old population.

The Academy of Fabry Disease in the Korean Society of Nephrology has developed evidence-based clinical practice guidelines to optimize the management and treatment of Fabry nephropathy. Although Fabry disease is a rare genetic disorder, the recent availability of effective therapeutic options, including enzyme replacement therapy and chaperone therapy, highlights the importance of early diagnosis and timely intervention. These guidelines were developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, with support from methodology experts. Clinical recommendations were derived through a systematic literature review addressing 11 key questions. These guidelines are intended to assist healthcare professionals, including nephrologists, in making informed, evidence-based clinical decisions to improve patient outcomes.

The aim of this study is to characterise the immunological features of preformed HLA-DQ DSAs and investigate their impact on post-transplant outcomes. Among 1540 ABO-compatible KT recipients with available high-resolution HLA typing at Seoul St. Mary's Hospital (January 2010-December 2024), 179 had preformed DSAs. Patients were classified into DQ group (n = 58), comprising those with DQ DSAs alone or in combination with other DSAs, and non-DQ (n = 121) group. We compared baseline DSA characteristics, desensitisation (DSZ) responses and post-transplant outcomes. The DQ group had a significantly higher proportion of re-transplant recipients. At baseline, DQ DSAs exhibited markedly higher MFI values compared to non-DQ DSAs. Following DSZ, 45.2% of DQ DSAs remained strong (MFI > 10,000), compared to only 2.8% of non-DQ DSAs. While the overall incidence of acute ABMR did not differ significantly between groups, a significant difference was observed in the temporal distribution and the characteristics of the associated DSAs. In early-onset ABMR, cases in the DQ group developed after the complete resolution of preformed DSAs, whereas those in the non-DQ group were associated with preformed DSAs. Late-onset ABMR occurred more frequently in the DQ group (41.7% vs. 10.0%, p = 0.024), and it developed with preformed DQ DSAs. Furthermore, allograft function showed a more rapid deterioration in the DQ group. Preformed DQ DSAs carry a higher immunological risk and exhibit greater resistance to treatment than non-DQ DSAs, and tend to cause late-onset acute ABMR rather than immediate post-transplant rejection. Therefore, more stringent immunological monitoring and immunosuppressive therapy are required.

Background:Efepoetin alfa (GC1113, GX-E2) is a long-acting recombinant human erythropoietin fused to a hybrid fragment crystallizable (hyFc) that prolongs systemic exposure via neonatal Fc receptor-mediated recycling. This active-controlled phase 2 trial evaluated efepoetin alfa and informed phase 3 starting dose selection for chronic kidney disease-related anemia in dialysis patients. Methods:In this multicenter, open-label, active-controlled trial, adults on hemodialysis (HD) or peritoneal dialysis (PD) with hemoglobin (Hb) levels <10 g/dL were randomized after erythropoiesis-stimulating agent discontinuation. Over 12 weeks, HD patients received intravenous efepoetin alfa (5 or 8 µg/kg once weekly [Q1W], 8 µg/kg every 2 weeks [Q2W]) or darbepoetin alfa (30 µg Q1W). PD patients received subcutaneous efepoetin alfa (5 or 8 µg/kg Q2W) or methoxy polyethylene glycol-epoetin beta (0.6 µg/kg Q2W). The primary endpoint was the mean Hb change from baseline after 12 weeks of treatment, and an exploratory dose-conversion ratio (DCR) analysis was performed in the PD cohort to inform phase 3 dosing. Results:Efepoetin alfa showed dose-dependent Hb increases. In the HD cohort, mean Hb increases were 3.19 g/dL for efepoetin alfa 5 and 8 µg/kg Q1W and 2.52 g/dL for darbepoetin alfa. In the PD cohort, mean Hb increases were 2.69 g/dL and 3.48 g/dL for efepoetin alfa 5 and 8 µg/kg Q2W, respectively, and 2.01 g/dL for the control group. Exploratory DCR analysis supported 4 µg/kg Q2W efepoetin alfa as the phase 3 starting dose. Conclusion:Efepoetin alfa demonstrated dose-dependent erythropoietic efficacy and an acceptable safety profile in dialysis patients, supporting dose-range characterization and phase 3 starting dose selection.

Background:ABO-incompatible kidney transplantation (ABOi KT) has become increasingly feasible; however, recipients with very high baseline isoagglutinin titers continue to pose substantial clinical challenges. Methods:We conducted a retrospective, two-center review of 15 patients who underwent ABOi KT with baseline anti-A/B immunoglobulin G titers ≥1:1024. All patients received rituximab, therapeutic plasma exchange, and a standardized immunosuppressive regimen. Clinical outcomes-including bleeding complications, biopsy-proven acute rejection (BPAR), opportunistic infections, graft function, and patient survival-were assessed. Results:The median patient age was 53 years (13 men, 2 women). All but one achieved a preoperative titer ≤1:32 after a median of 10 apheresis sessions (range, 7-16). Two patients required graft nephrectomy due to severe postoperative bleeding. Five patients developed BPAR, comprising T cell-mediated and/or antibody-mediated rejection episodes; notably, only one had a titer of 1:1024 at rejection, while the remainder had titers ≤1:16. Regarding opportunistic viral infections, seven patients developed concurrent cytomegalovirus (CMV) and BK viremia, two had CMV alone, and two had isolated BK viremia. Over a median 9.18-year follow-up (range, 0.04-16.45 years), three experienced graft loss-two from chronic rejection at 6 and 15 years, and one due to sepsis-associated acute kidney injury at 15 years. Two patients died during follow-up: one from cardiovascular disease at 1.2 years and the other from pneumonia at 6 years. Conclusions:Despite extremely high baseline isoagglutinin titers, ABOi KT can achieve durable graft survival in carefully selected patients; however, it remains a high-risk procedure carrying a substantial burden of bleeding and infectious complications.

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Background:Calcineurin inhibitor (CNI) toxicity is a significant cause of graft dysfunction in kidney transplant recipients, yet distinguishing it from acute rejection (AR) and acute tubular necrosis (ATN) remains challenging. This study investigated the use of urinary mRNA biomarkers as a noninvasive tool for identifying CNI toxicity. Methods:We retrospectively enrolled 110 kidney transplant recipients and classified them into four groups based on pathological findings: stable graft function (n=35), CNI toxicity (n=25), AR (n=30), and ATN (n=20). Candidate biomarkers were selected using the GEO database. Urinary mRNA was extracted from cell pellets, reverse-transcribed, and quantified by real-time polymerase chain reaction. Results:Estimated glomerular filtration rates were comparable among the CNI toxicity, AR, and ATN groups. Four transcripts (LTF, NNMT, WFDC2, and HIF1A) were identified as candidate biomarkers. Urinary mRNA levels of LTF, NNMT, and HIF1A were significantly lower in the CNI toxicity group than the AR group. NNMT and HIF1A levels were also significantly lower than those observed in the ATN group. In contrast, WFDC2 levels did not differ significantly across groups. A three-gene signature (LTF, NNMT, and HIF1A) effectively differentiated CNI toxicity from AR and ATN (area under the curve [AUC], 0.867; 95% confidence interval [CI], 0.787-0.947) and significantly enhanced the diagnostic performance of the clinical variable-based model (AUC increased from 0.776; 95% CI, 0.660-0.892, to 0.934; 95% CI, 0.881-0.986). Conclusions:Urinary mRNA levels of LTF, NNMT, and HIF1A may serve as useful biomarkers for identifying CNI toxicity in kidney transplant recipients with graft dysfunction.

Background: Sensitization acts as an immunological barrier to successful kidney transplantation (KT). We aim to investigate the efficacy and safety of bortezomib-based desensitization (BOZ-DSZ) in both highly sensitized living donor KT (LDKT) and deceased donor KT (DDKT). Methods: We applied BOZ-DSZ to 20 highly sensitized patients-14 LDKT and six DDKT candidates-and analyzed the change in anti-human leukocyte antigen (HLA) antibody, the success rate of transplantation, and posttransplant outcomes including biopsy-proven allograft rejection (BPAR) rate, infectious complication, and allograft survival. Results: Among 14 LDKT candidates, the peak mean fluorescence intensity (MFI) level of donor-specific anti-HLA antibody (HLA-DSA) decreased in 10 patients (p < 0.05), and the success rate of KT was 92.9% (13 of 14). Incidence of BPAR within the first post transplant year was 53.8% (7 of 13), and all such cases were rescued by antirejection treatment. One case resulted in mortality due to pneumonia, and there was one allograft failure during the follow-up of 34 months (range, 6-129 months). Among the six DDKT candidates, the peak MFI level of HLA-DSA showed a significant decrease after DSZ in five patients (p = 0.098), and the success rate of KT was 50.0% (3 of 6). One BPAR case (33.3%) occurred within the first posttransplant year and was successfully treated. There was one case of Cytomegalovirus viremia, and there was no allograft failure during the 36-month follow-up (range, 17-42 months). Conclusion: BOZ-DSZ is effective and safe in terms of successful DSZ, infectious complications, and allograft outcomes for both highly sensitized LDKT and DDKT candidates.

Cytomegalovirus (CMV) infection is a frequent complication after kidney transplantation (KT) and has various effects on recipient and graft survival. Although guidelines recommend anti-viral prophylaxis with ganciclovir or valganciclovir, there is a demand for alternative regimen for CMV prevention. We investigated the effects of a 3-month valacyclovir-based prophylaxis on CMV infection and clinical outcomes in KT recipients using a nationwide cohort. Overall, 2,584 KT recipients from 20 transplant centers registered with the Korean Organ Transplantation Registry between May 2014 and December 2019 were analyzed in this study. The recipients were divided into valacyclovir prophylaxis and non-prophylaxis groups, a 1:3 propensity score matching was performed, and 1,036 recipients (291 and 745 in the prophylaxis and non-prophylaxis groups, respectively) were analyzed. The impact of valacyclovir-based prophylaxis on CMV after KT, other clinical outcomes, and the risk factors for CMV infection development were investigated. The prophylaxis group showed a lower incidence of CMV infection and rejection compared to the non-prophylaxis group (3.64 vs. 10.25 events/100 person-years and 1.85 vs. 7.27 events/100 person-years, respectively). Valacyclovir prophylaxis, donor age, deceased donor, length of hospitalization after KT, anti-thymocyte globulin use, and CMV serological mismatch between the donor and recipient were independent risk factors for CMV infection after KT. Valacyclovir prophylaxis after KT significantly reduced CMV infection and rejection. We suggest that valacyclovir could be considered as an alternative strategy for CMV prophylaxis after KT. However, our study has limitations, including its retrospective design, variability in valacyclovir dosing and CMV monitoring, and unassessed confounding factors. Further prospective studies with standardized protocols and larger cohorts are needed to validate our findings.

BackgroundThe revised 2023 guidelines from the International Society for Peritoneal Dialysis (ISPD) emphasize salvage methods for treating refractory catheter-related infections, or mechanical catheter damage. This approach preserves the existing catheter by manipulating only the outer cuff above the peritoneum, avoiding hemodialysis transfer. We investigated the effectiveness of the partial replantation technique.MethodsIn this retrospective single-center study (January 2021 - December 2023), outcomes for nine patients undergoing salvage methods were compared with 58 patients receiving de novo catheter insertion. We assessed exit-site infection (ESI), tunnel infection (TI), peritonitis, and catheter dysfunction. The salvage method entailed distal cutting of the impaired catheter and attaching a new segment using a connector with a PD adaptor and transfer set.ResultsNine patients (four males, mean age 56 years, average PD duration 66 months) employed the salvage method. Post-procedure, one patient (11.1%) reported ESI, one (11.1%) experienced TI, three (33.3%) developed peritonitis, and two (22.2%) required catheter removal. No procedural complications or catheter dysfunctions were observed. In the control group, ESI occurred in six patients (10.3%), TI in one (1.7%), peritonitis in 11 (19.0%), catheter removal in seven (12.1%), and catheter dysfunction in one (1.7%). Kaplan-Meier analysis showed no statistical difference between the groups: ESI (p = 0.306), TI (p = 0.094), peritonitis (p = 0.838), catheter dysfunction (p = 0.694), and catheter removal (p = 0.393).ConclusionsThis study supports the non-inferiority and effectiveness of the salvage method compared to de novo insertion in managing ESI or TI and mechanical catheter damage.

Background: Skin rash is a common adverse event in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with apalutamide. This study aims to investigate the incidence rate of skin rash and the predictive value of inflammation markers for skin rash in real-world Korean patients. Materials and Methods: We conducted a retrospective analysis of patients with prostate cancer (PCa) who received apalutamide across 18 institutions in Korea, with a follow-up period of at least three months. A total of 218 patients were evaluated. Results: Among the 214 patients analyzed, 78 (36.4%) developed a skin rash. The severity of the rash was classified as grade 1 (G1) in 27 patients (12.6%), grade 2 (G2) in 29 patients (13.5%), and grade 3 (G3) in 22 patients (10.3%). The median time to onset of any skin rash was 65.5 days (interquartile range, IQR 31.0-88.0). The monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation response index (SIRI) were significantly higher in the G2 plus G3 group compared to the no rash plus G1 group (p=0.006, p=0.013, respectively) before apalutamide treatment. After 3 months, platelet-to-lymphocyte ratio (PLR) and SIRI were significantly higher in the G2 plus G3 group compared to the no rash plus G1 group (p=0.010, p=0.025, respectively) Conclusions: In a real-world cohort of Korean patients, skin rash occurred in 36.4% of cases, with a median time to onset of 65.5 days. Grade 3 skin rash developed in 10.3% of cases. While MLR and SIRI were significantly higher in the G2 plus G3 group, these markers cannot be considered reliable predictors due to a low area under the curve (AUC < 0.7) before apalutamide treatment. However, increased levels of PLR, SII, and SIRI could potentially be useful for monitoring for the risk of severe rash development in these patients.

BACKGROUND AIMS:This study evaluated the safety and efficacy of allogenic human bone marrow-derived mesenchymal stem cell (hBM-MSC) therapy in kidney transplant recipients (KTR) with chronic active antibody-mediated rejection (cABMR). METHODS:Seven cABMR patients received four infusions of hBM-MSC (1 × 10⁶ cells/kg), one every other week. The primary outcome was clinical safety, focusing on short-term adverse events. Secondary outcomes included changes in allograft function, mean fluorescence intensity (MFI) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA), allogenic immune response as determined by ELISPOT, lymphocyte subset analysis, infection-free survival, and graft survival compared to 18 historical controls via propensity score matching. RESULTS:Seven patients received hBM-MSC therapy at a median of 5.4 years (range, 1.6-15.3) after KT and 8.5 months (range, 1.2-20.6) after the diagnosis of cABMR. Six patients completed treatment, and one patient received two doses. No immediate side effects were observed. One patient developed Pneumocystis jirovecii pneumonia (PJP) 3 weeks after treatment and died 6 weeks post-treatment. Among those who completed therapy, the eGFR slope shifted from -Δ16.6% to -Δ2.4% over the 6 month periods before and after treatment, suggesting a stabilization of eGFR decline, proteinuria decreased, and MFI of HLA-DSA declined. T-cell subset analysis showed increased CD8+CD45RA+CCR7- T cells and CD4+CD25+CD127low T cells with decreased CD8+CCR7+CD45RO+/CD45RA+ T cells. Kaplan-Meier analysis demonstrated no significant difference in infection-free survival or death-censored graft survival compared to those of the propensity score-matched control group. No significant difference in infection-free survival or death-censored graft survival compared to those of the propensity score-matched control group. CONCLUSIONS:hBM-MSC therapy was generally well tolerated for KTR with cABMR and demonstrated favorable immunomodulatory effects. Larger, controlled trials with extended period are required to validate these findings and better define the role of hBM-MSC therapy for cABMR.

Purpose: Accurate survival prediction is essential for optimizing the treatment planning in patients with castration-resistant prostate cancer (CRPC). However, the traditional statistical models often underperform due to limited variable inclusion and an inability to account for complex, multidimensional data interactions. Methods: We retrospectively collected 46 clinical, laboratory, and pathological variables from 801 patients with CRPC, covering the disease course from the initial disease diagnosis to CRPC progression. Multiple machine learning (ML) models, including random survival forests (RSFs), XGBoost, LightGBM, and logistic regression, were developed to predict cancer-specific mortality (CSM), overall mortality (OM), and 2- and 3-year survival status. The dataset was split into training and test cohorts (80:20), with 10-fold cross-validation. The performance was assessed using the C-index for regression models and the AUC, accuracy, precision, recall, and F1-score for classification models. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). Results: Over a median follow-up of 24 months, 70.6% of patients experienced CSM. RSFs achieved the highest C-index in the test set for both CSM (0.772) and OM (0.771). For classification tasks, RSFs demonstrated a superior performance in predicting 2-year survival, while XGBoost yielded the highest F1-score for 3-year survival. The SHAP analysis identified time to first-line CRPC treatment and hemoglobin and alkaline phosphatase levels as key predictors of survival outcomes. Conclusion: The RSF and XGBoost ML models demonstrated a superior performance over that of traditional statistical methods in predicting survival in CRPC. These models offer accurate and interpretable prognostic tools that may inform personalized treatment strategies. External validation and the integration of emerging therapies are warranted for broader clinical applicability.

Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.

Background Intradialytic hypotension (IDH) is the primary complication of haemodialysis (HD); however, its diverse pathophysiology and inconsistent definitions complicate its prediction. Despite attempts using the heart rate variability (HRV) test for IDH prediction, studies on its usefulness for predicting IDH diagnosed per the nadir 90 criterion are lacking. We aimed to evaluate HRV test efficacy and reproducibility in predicting IDH based on the nadir 90 criterion.Methods Seventy patients undergoing HD participated in this multicentre prospective observational study. The HRV test was performed during non-HD periods and IDH was monitored during 12 HD sessions. IDH was diagnosed according to the nadir 90 criterion, defined as a decrease in systolic blood pressure of <= 90 mmHg during HD. After monitoring, the HRV test was repeated. An HRV-IDH index was developed using multivariate logistic regression analysis employing HRV test parameters. The predictive power of the HRV-IDH index was analysed using the area under the receiver operating characteristics curve (AUROC). Reproducibility was evaluated using correlation analysis of two HRV tests on the same patient.Results There were 37 and 33 patients in the IDH and non-IDH groups, respectively. The HRV-IDH index predicted IDH occurrence with AUROCs of 0.776 and 0.803 for patients who had experienced at least one or repeated IDH episodes, respectively. Spearman's correlation coefficient for HRV-IDH indices was 0.859 for the first and second HRV tests.Conclusions The HRV test holds promise for predicting IDH, particularly for patients with recurring IDH diagnosed based on the nadir 90 criterion. Graphical Abstract

Sensitization to HLA can result in allograft loss for kidney transplantation (KT) patients. Therefore, it is required to develop an appropriate desensitization (DSZ) technique to remove HLA-donor-specific anti-HLA antibody (DSA) before KT. The aim of this research was to investigate whether combined use of the IL-6 receptor-blocking antibody, tocilizumab (TCZ), and bone-marrow-derived mesenchymal stem cells (BM-MSCs) could attenuate humoral immune responses in an allo-sensitized mouse model developed using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and treated with TCZ, BM-MSC, or both TCZ and BM-MSC. We compared HLA.A2-specific IgG levels and subsets of T cells and B cells using flow cytometry among groups. HLA.A2-specific IgG level was decreased in all treated groups in comparison with that in the allo-sensitized control (Allo-CONT) group. Its decrease was the most significant in the TCZ + BM-MSC group. Regarding the B cell subset, combined use of TCZ and BM-MSC increased proportions of pre-pro B cells but decreased proportions of mature B cells in BM (p < 0.05 vs. control). In the spleen, an increase in transitional memory was observed with a significant decrease in marginal, follicular, and long-lived plasma B cells (p < 0.05 vs. control) in the TCZ + BM-MSC group. In T cell subsets, Th2 and Th17 cells were significantly decreased, but Treg cells were significantly increased in the TCZ+BM-MSC group compared to those in the Allo-CONT group in the spleen. Regarding RNA levels, IL-10 and Foxp3 showed increased expression, whereas IL-23 and IFN-γ showed decreased expression in the TCZ + BM-MSC group. In conclusion, combined use of TCZ and BM-MSC can inhibit B cell maturation and up-regulate Treg cells, finally resulting in the reduction of HLA.A2-specific IgG in a highly sensitized mouse model. This study suggests that the combined use of TCZ and BM-MSC can be proposed as a novel strategy in a desensitization protocol for highly sensitized patients.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Background Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis.Methods We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24 h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids.Results During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058).Conclusions Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis.