Validation of prediction model for successful discontinuation of continuous renal replacement therapy: a multicenter cohort study.

Background: Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. Methods: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days in 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. Results: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71-0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and high-score groups, respectively. The model performance was good in four cohorts (AUROC, 0.73-0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. Conclusion: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Mortality of elderly patients with acute kidney injury undergoing continuous renal replacement therapy: is age a risk factor?

Background: Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. Methods: Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65-74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. Results: Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99-1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30-0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18-10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02-2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36-0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28-day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. Conclusion: Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

Single-cell RNA sequencing revealed the role of the Th17 pathway in the development of anti- human leukocyte antigen antibodies in a highly sensitized mouse model.

Background: The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse. Methods: For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them. Results: We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN. Conclusion: Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

Usefulness of the heart rate variability test in predicting intradialytic hypotension in patients undergoing chronic haemodialysis.

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.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

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.

Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction.

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.

Management of Immunosuppressive Therapy in Kidney Transplant Recipients with Sepsis: A Multicenter Retrospective Study.

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.

Combined Use of Tocilizumab and Mesenchymal Stem Cells Attenuate the Development of an Anti-HLA-A2.1 Antibody in a Highly Sensitized Mouse Model.

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.

Prediction of diabetes mellitus after kidney transplantation using patient-specific induced pluripotent stem cells.

BACKGROUND: Multiple risk factors are involved in new-onset diabetes mellitus (DM) after organ transplantation; however, their ability to predict clinical prognosis remains unclear. Therefore, we investigated whether patient-specific induced pluripotent stem cells (iPSCs) could help predict DM development before performing kidney transplantation (KT). METHODS: We first performed whole transcriptome and functional enrichment analyses of KT patient-derived iPSCs. Our results revealed that insulin resistance, type 2 DM, and transforming growth factor beta signaling pathways are associated between the groups of DM and non-DM. We next determined whether the genetic background was associated with development of iPSCs into pancreatic progenitor (PP) cells. RESULTS: The levels of differentiation-related key markers of PP cells were significantly lower in the DM group than in the non-DM group. Moreover, the results of tacrolimus toxicity screening showed a significant decrease in the number of PP cells of the DM group compared with the non-DM group, suggesting that these cells are more susceptible to tacrolimus toxicity. CONCLUSION: Taken together, these results indicate that PP cells of the DM group showed low developmental potency accompanied by a significantly different genetic background compared with the non-DM group. Thus, genetic analysis can be used to predict the risk of DM before KT.

Oncological Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide with versus without Confirmatory Bone Scan.

PURPOSE: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. MATERIALS AND METHODS: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. RESULTS: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). CONCLUSION: Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

A prospective, randomized, open-label, parallel trial comparing the efficacy of α-blocker or 5α-reductase inhibitor withdrawal to continued combination therapy on the maintenance of lower urinary tract symptoms in men with benign prostatic hyperplasia.

BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.

Post Hoc Analysis of Rapid and Deep Prostate-specific Antigen Decline and Patient-reported Health-related Quality of Life in SPARTAN and TITAN Patients with Advanced Prostate Cancer.

BACKGROUND: Adding apalutamide to androgen-deprivation therapy (ADT) resulted in a rapid (at 3- and 6-mo treatment) and deep prostate-specific antigen (PSA) decline (to ≤0.2 ng/ml or ≥90% from baseline), improved overall survival, reduced risk of disease progression, and prolonged health-related quality of life (HRQoL) in nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN and metastatic castration-sensitive PC (mCSPC) in TITAN. OBJECTIVE: To evaluate the association of a rapid, deep PSA decline at 3 and 6 mo achieved with the addition of apalutamide to ADT with patient-reported outcomes (PROs) in SPARTAN and TITAN. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of SPARTAN and TITAN PRO data was performed. INTERVENTION: Apalutamide versus placebo plus concurrent ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PROs were assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P; SPARTAN and TITAN), Brief Pain Inventory-Short Form (BPI-SF; TITAN), and Brief Fatigue Inventory (BFI; TITAN) at baseline, prespecified cycles during treatment, and after progression for ≤1 yr. The association between a deep PSA decline at landmark 3 or 6 mo of apalutamide and the time to worsening of PROs was assessed using the Kaplan-Meier methodology and Cox proportional-hazard modeling. RESULTS AND LIMITATIONS: Among 806 SPARTAN and 525 TITAN apalutamide-treated patients, the median treatment duration was 32.9 and 39.3 mo, respectively. Patients achieving a deep PSA decline at 3 mo had longer time to worsening in FACT-P total, FACT-P physical well-being, BPI-SF worst pain intensity, or BFI worst fatigue intensity. The 6-mo PSA decline results were similar. Limitations of patient characteristics in clinical studies should be considered. CONCLUSIONS: Attaining a deep and rapid PSA decline at 3 mo with apalutamide plus ADT was associated with longer preservation of overall HRQoL and physical well-being in nmCRPC and mCSPC. PATIENT SUMMARY: Quality of life is maintained in individuals with advanced prostate cancer who achieve a deep prostate-specific antigen decline at 3 mo of apalutamide plus drugs that lower male sex hormones.

Salvage treatment of forearm arteriovenous fistula with small caliber inflow distal artery by percutaneous transluminal angioplasty.

BACKGROUND: Dysfunctional distal arteriovenous fistulas (AVFs) with small caliber distal inflow arteries theoretically require percutaneous transluminal angioplasty (PTA) throughout the entire arterial length. However, in clinical practice, whole distal inflow arterial PTA is not frequently performed due to concerns about possible arterial rupture. Therefore, we investigated the safety and efficacy of this procedure at our center, comparing it with the standard venous PTA. METHODS: From March 2017 to December 2022, 48 cases of distal AVF salvaged by whole distal inflow arterial PTA were assigned into a treatment group and 121 cases of distal AVF salvaged by venous standard PTA not involving the whole inflow artery were assigned into a control group. These two groups were then compared. RESULTS: Those in the treatment group (who received whole distal inflow arterial PTA) were older than those in the control group (mean age, 69 vs 59 years, p < 0.001). Otherwise, differences between the two groups were unremarkable. After the salvage treatment, primary patency seemed to decrease in the treatment group with whole distal inflow arterial PTA compared to the control group with conventional PTA, although such decrease was not significant (p = 0.072). However, primary assisted patency and secondary patency were comparable between the two groups (p = 0.350 and p = 0.590, respectively). And in the treatment group, only one arterial dissection occurred, which was successfully managed with balloon tamponade so that no distal AVF was abandoned due to complications following whole distal inflow arterial PTA. CONCLUSION: Whole distal inflow arterial PTA is an effective and safe option for distal AVF salvage with a narrowed inflow artery, frequently refractory to conventional venous PTA.

Effects of resection volume on postoperative micturition symptoms and retreatment after transurethral resection of the prostate.

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.

Pretransplant BKV-IgG serostatus and BKV-specific ELISPOT assays to predict BKV infection after kidney transplantation.

Introduction: Polyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection. Methods: A total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3). BK viremia was diagnosed when blood BKV-DNA of 104 copies/mL or more was detected during follow-up periods. Results: Anti-BKV IgG antibody was detected in 74 (79.6%) of 93 KTRs and in 68 (73.1%) of 93 KT donors. A greater percentage of KTRs who received allograft from donors with high levels of anti-BKV IgG had posttransplant BK viremia (+) than KTRs from donors with low anti-BKV IgG (25.5% [12/47] vs. 4.3% [2/46], respectively; P = 0.007). Pretransplant total BKV-ELISPOT results were lower in BK viremia (+) patients than in patients without viremia (-) 20.5 [range 9.9-63.6] vs. 72.0 [43.2 - 110.8]; P = 0. 027). The sensitivity and specificity of the total BKV-ELISPOT assay (cut-off ≤ 53 spots/3×105 cells) for prediction of posttransplant BK viremia were 71.4 (95% CI: 41.9-91.6) and 54.4 (42.8-65.7), respectively. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results improved specificity to 91.1%. Discussion: Our study highlights the importance of pretransplant BKV-IgG serostatus and BKV-specific CMI in predicting posttransplant BKV infection in KTRs. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results predicted BK viremia after KT. Pretransplant identification of patients at highrisk for BK viremia could enable timely interventions and improve clinical outcomes of KTRs.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

Modeling of FAN1-Deficient Kidney Disease Using a Human Induced Pluripotent Stem Cell-Derived Kidney Organoid System.

Karyomegalic interstitial nephritis (KIN) is a genetic kidney disease caused by mutations in the FANCD2/FANCI-Associated Nuclease 1 (FAN1) gene on 15q13.3, which results in karyomegaly and fibrosis of kidney cells through the incomplete repair of DNA damage. The aim of this study was to explore the possibility of using a human induced pluripotent stem cell (hiPSC)-derived kidney organoid system for modeling FAN1-deficient kidney disease, also known as KIN. We generated kidney organoids using WTC-11 (wild-type) hiPSCs and FAN1-mutant hiPSCs which include KIN patient-derived hiPSCs and FAN1-edited hiPSCs (WTC-11 FAN1+/-), created using the CRISPR/Cas9 system in WTC-11-hiPSCs. Kidney organoids from each group were treated with 20 nM of mitomycin C (MMC) for 24 or 48 h, and the expression levels of Ki67 and H2A histone family member X (H2A.X) were analyzed to detect DNA damage and assess the viability of cells within the kidney organoids. Both WTC-11-hiPSCs and FAN1-mutant hiPSCs were successfully differentiated into kidney organoids without structural deformities. MMC treatment for 48 h significantly increased the expression of DNA damage markers, while cell viability in both FAN1-mutant kidney organoids was decreased. However, these findings were observed in WTC-11-kidney organoids. These results suggest that FAN1-mutant kidney organoids can recapitulate the phenotype of FAN1-deficient kidney disease.

Impact of Induction Immunosuppressants on T Lymphocyte Subsets after Kidney Transplantation: A Prospective Observational Study with Focus on Anti-Thymocyte Globulin and Basiliximab Induction Therapies.

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4+ T cell expression decreased significantly compared with that in the BXM group. However, CD4+CD161+ and CD4+CD25+CD127low T cell expression levels increased significantly. In the CD8+ T cell subset, a decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4+CD161+ and CD4+CD25+CD127low T cells and an early decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cells, some of which are associated with acute rejection.