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Sang-Jin Park,1,* Seung Ro Han,2,3,* Yun Hee Kang,2,3,* Eun-Jin Lee,1 Eu-Gene Kim,1 Hyobong Hong,4 Jae-Chan Jeong,4 Myung-Shin Lee,2,3 Seung-Hoon Lee,2,5 Dae-Yong Song1 1Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea; 2Eulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, Korea; 3Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, Korea; 4Artifcial Intelligence Research Laboratory, Electronics and Telecommunications Research Institute (ETRI), Daejeon, Korea; 5Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea*These authors contributed equally to this workCorrespondence: Seung-Hoon Lee, Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea, Tel +82-42-259-1612, Fax +82-42-259-1669, Email nslsh@eulji.ac.kr Dae-Yong Song, Department of Anatomy and Neuroscience, Eulji University School of Medicine, Daejeon, Korea, Tel +82-42-259-1622, Fax +82-42-259-1669, Email dysong@eulji.ac.krPurpose: Magnetic particle imaging (MPI) is an emerging radiation-free, non-invasive three-dimensional tomographic technology that can visualize the concentrations of superparamagnetic iron oxide nanoparticles (SPIONs). To verify the applicability of the previously proposed point-of-care testing MPI (PoCT-MPI) in medical diagnosis and therapeutics, we imaged SPIONs in animal tumor models.Methods: CT26 or MC38 mouse colon carcinoma cells (2 × 106 cells) were subcutaneously injected into the right flank of BALB/c mice. SPIONs were either injected directly into the tumor lesions in the intratumoral group or through tail veins in the intravenous group. CT26 and MC38 tumor models were examined both intratumorally and intravenously to confirm the biological availability of SPIONs using PoCT-MPI.Results: Signals were observed in the tumor lesions from day 1 to day 7. This is the first study to successfully image the pathological region and show the biodistribution of SPIONs in CT26 tumor models using the recently developed PoCT-MPI technology. Furthermore, MC38 tumor models were examined, resulting in similar images to those of the CT26 tumor model in both intratumoral and intravenous groups.Conclusion: The present study demonstrates the biological applicability of PoCT-MPI, which promises to be a powerful diagnostic and therapeutic technique in biomedical imaging.Keywords: colon cancer, syngeneic mouse tumor model, point-of-care testing MPI, diagnostics

Purpose of Review: Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD., Recent Findings: Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8 + T cells, classical monocytes, and eosinophils., Summary: Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Decreased lean body mass or muscle mass is associated with decreased bone mineral density in individuals with preserved renal function. However, the association between muscle mass and bone mineral density in chronic kidney disease (CKD) patients is not well known. The aim of this study was to assess the relationship between muscle mass estimated from urine creatinine (UCr) and bone mineral density in Korean CKD patients., Methods: This cross-sectional study analyzed 1872 participants from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. Participants underwent UCr (g/day) and bone mineral density measurements, which were measured at the lumbar spine, total hip, and femoral neck by dual-energy X-ray absorptiometry. Patients were divided into three groups according to the tertiles of 24 h UCr (T1-T3)., Results: The mean values for 24 h urine creatinine of T1, T2, and T3 were 0.83 ± 0.23 g, 1.18 ± 0.24 g, and 1.55 ± 0.38 g, respectively. A total of 172 patients were diagnosed with osteoporosis. The number of patients in each group was 92 (14.4%) in T1, 45 (7.3%) in T2, and 35 (5.7%) in T3. The odds ratio (95% confidence interval) for osteoporosis was 0.37 (0.20-0.69) for 1 g/day increase of UCr. Compared with T1, the odds ratios (95% confidence interval) for osteoporosis were 0.58 (0.39-0.87) for T2 and 0.51 (0.32-0.80) for T3., Conclusion: Low 24-h UCr was associated with low bone mineral density. Low 24 h UCr was significantly and independently associated with osteoporosis in Korean pre-dialysis CKD patients. Further research is warranted to verify the influence of muscle mass on bone health in CKD., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Cannabis sativa cultivars can be classified as marijuana or hemp, depending on its amount of the psychoactive cannabinoid Δ 9 -tetrahydrocannabinolic acid (THCA). Hemp Cheungsam is a non-drug type Cannabis sativa that is characterized by low THCA content. However, the transcripts and expression profile of cannabinoid biosynthesis pathway genes of hemp Cheungsam have not been investigated., Methods: RNA-sequencing (RNA-seq) was performed on three different tissue types (flower, leaf, and stem) of hemp Cheungsam to understand their transcriptomes. The expression of cannabinoid biosynthesis pathway genes was further analyzed in each tissue type. Multiple sequence alignment and conserved domain analyses were used to investigate the homologs of cannbinoid biosynthesis genes., Results: We found that the cannabinoid biosynthesis pathway was mainly expressed in the flowers of hemp Cheungsam, similar to other Cannabis cultivars. However, expression of cannabidiolic acid (CBDA) synthase was much higher than THCA synthase and cannabichromenic acid (CBCA) synthase, suggesting that the transcription profile favors CBDA biosynthesis. Sequence analysis of cannabinoid biosynthesis pathway genes suggested the identity of orthologs in hemp Cheungsam., Conclusions: Cannabinoid biosynthesis in hemp Cheungsam mostly occurs in the flowers, compared to other plant organs. While CBDA synthase expression is high, THCA and CBCA synthase expression is considerably low, indicating lesser THCA biosynthesis and thus low THCA content. Sequence analysis of key genes (CBDA, THCA, and CBCA synthases) of the cannabinoid biosynthetic pathway indicates that orthologs are present in hemp Cheungsam., (© 2024. The Author(s).)

Plant calli, a perpetually undifferentiated cell culture, have defects in maintaining their genetic fidelity during prolonged tissue culture. Cryopreservation using ice-binding proteins (IBP) is a potential solution. Despite a few studies on cryopreservation using IBPs in plant calli, detailed insights into the intracellular metabolism during freezing, thawing, and re-induction remain sparse. This study investigated and employed IBP from polar yeast Leucosporidium sp. (LeIBP) in the cryopreservation process across diverse taxa, including gymnosperms, monocots, dicots, and woody plants. Molecular-level analyses encompassing reactive oxygen species levels, mitochondrial function, and ATP and lipophilic compounds content were conducted. The results across nine plant species revealed the effects of LeIBP on callus competency post-thawing, along with enhanced survival rates, reactive oxygen species reduction, and restored metabolic activities to the level of those of fresh calli. Moreover, species-specific survival optimization with LeIBP treatments and morphological assessments revealed intriguing extracellular matrix structural changes post-cryopreservation, suggesting a morphological strategy for maintaining the original cellular states and paracrine signaling. This study pioneered the comprehensive application of LeIBP in plant callus cryopreservation, alleviating cellular stress and enhancing competence. Therefore, our findings provide new insights into the identification of optimal LeIBP concentrations, confirmation of genetic conformity post-thawing, and the intracellular metabolic mechanisms of cryopreservation advancements in plant research, thereby addressing the challenges associated with long-term preservation and reducing labor-intensive cultivation processes. This study urges a shift towards molecular-level assessments in cryopreservation protocols for plant calli, advocating a deeper understanding of callus re-induction mechanisms and genetic fidelity post-thawing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another., Methods: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival., Results: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy., Conclusions: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed., Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria., Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50-1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06-4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05-4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10-2.85), without a substantial increase in the risk of decreased renal function., Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Background and Aims: High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT)., Methods: We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1-199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT., Results: During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02-2.87) and 2.55 (95 % CI, 1.07-6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis., Conclusions: CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ribonucleotide Reductase (RNR) is a rate-limiting enzyme in the production of deoxyribonucleoside triphosphates (dNTPs), which are essential substrates for DNA repair after radiation damage. We explored the radiosensitization property of RNR and investigated a selective RRM2 inhibitor, 3-AP, as a radiosensitizer in the treatment of metastatic pNETs. We investigated the role of RNR subunit, RRM2, in pancreatic neuroendocrine (pNET) cells and responses to radiation in vitro. We also evaluated the selective RRM2 subunit inhibitor, 3-AP, as a radiosensitizer to treat pNET metastases in vivo. Knockdown of RNR subunits demonstrated that RRM1 and RRM2 subunits, but not p53R3, play significant roles in cell proliferation. RRM2 inhibition activated DDR pathways through phosphorylation of ATM and DNA-PK protein kinases but not ATR. RRM2 inhibition also induced Chk1 and Chk2 phosphorylation, resulting in G1/S phase cell cycle arrest. RRM2 inhibition sensitized pNET cells to radiotherapy and induced apoptosis in vitro. In vivo, we utilized pNET subcutaneous and lung metastasis models to examine the rationale for RNR-targeted therapy and 3-AP as a radiosensitizer in treating pNETs. Combination treatment significantly increased apoptosis of BON (human pNET) xenografts and significantly reduced the burden of lung metastases. Together, our results demonstrate that selective RRM2 inhibition induced radiosensitivity of metastatic pNETs both in vitro and in vivo. Therefore, treatment with the selective RRM2 inhibitor, 3-AP, is a promising radiosensitizer in the therapeutic armamentarium for metastatic pNETs., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chronic kidney disease (CKD) patients are hospitalized for various conditions. Hospitalization increases the readmission rate and mortality rate, seriously deteriorating patients' quality of life. Consequently, it is crucial to analyze the reasons for hospitalization in CKD patients from a broader perspective according to CKD grade., Methods: This is a prospective cohort study of CKD patients entitled the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). A total of 2,238 patients were examined, and the reasons for hospitalization were classified into 16 disease categories. The incidence rate ratio (IRR) according to CKD stage was compared using negative bimodal regression analysis., Results: The all-cause hospitalization incidence was 184.96 per 1,000 person-years. The most common reason for hospitalization was circulatory system disease, followed by infection and digestive system disease. Among hospitalizations for acute kidney injury, endocrine-nutrition-metabolic-related illness, blood-related disease, and diseases of the nervous system and sensory organs, IRR increased as CKD grade advanced. The incidence of ophthalmologic surgery during hospitalization increased according to the CKD stage. The IRR of KNOW-CKD patients was 6.19 (95% confidence interval, 5.92-6.48; p < 0.001) compared with the general population., Conclusion: This in-depth analysis of hospitalizations among CKD patients confirmed that CKD patients were hospitalized for various reasons, such as metabolic, ophthalmic, and hematologic diseases. Early detection and intervention regarding causative diseases of CKD are important to reduce the hospitalization burden and improve patients' quality of life.

We present two magnetic particle imaging (MPI) systems with bore sizes of 75 mm and 100 mm, respectively, using three-dimensionally arranged permanent magnets for excitation and frequency mixing magnetic detection (FMMD) coils for detection. A rotational and a translational stage were combined to move the field free line (FFL) and acquire the MPI signal, thereby enabling simultaneous overall translation and rotational movement. With this concept, the complex coil system used in many MPI systems, with its high energy consumption to generate the drive field, can be replaced. The characteristic signal of superparamagnetic iron oxide (SPIO) nanoparticles was generated via movement of the FFL and acquired using the FMMD coil. The positions of the stages and the occurrence of the f 1 + 2 f 2 harmonics were mapped to reconstruct the spatial location of the SPIO. Image reconstruction was performed using Radon and inverse Radon transformations. As a result, the presented method based on mechanical movement of permanent magnets can be used to measure the MPI, even for samples as large as 100 mm. Our research could pave the way for further technological developments to make the equipment human size, which is one of the ultimate goals of MPI.

Introduction: Kidney transplantation (KT) improves the cardiovascular outcomes of patients with end-stage kidney disease. However, cardiovascular disease remains the leading cause of premature death and graft loss in KT recipients (KTRs) with diabetes. We evaluated the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in KTRs with diabetes., Methods: A total of 750 KTRs with diabetes were enrolled from 6 tertiary hospitals. Among them, 129 patients (17.2%) were prescribed SGLT2i. The primary outcome was the incidence of major adverse cardiovascular events (MACE), which comprised myocardial infarction (MI), death from cardiovascular causes, hospitalization for heart failure, and stroke. Multivariable Cox regression analysis and propensity score matching were used to investigate the effect of SGLT2i on clinical outcomes., Results: In the matched cohort, MACE occurred in 5 patients (3.9%) in the SGLT2i group and 15 patients (11.8%) in the non-SGLT2i group, out of 127 patients in each group over 55.3 months. The incidence of MACE and MI was lower in the SGLT2i group than in the non-SGLT2i group ( P  = 0.036 and 0.008, respectively). In multivariate analysis, the SGLT2i group had a lower risk of MACE and MI than the non-SGLT2i group (adjusted hazard ratio [HR], 0.30 and 0.04; 95% confidence interval [CI], 0.10-0.88 and 0.004-0.40; P  = 0.028 and 0.006, respectively). There was no difference in the incidence of urinary tract infection (UTI) between the 2 groups., Conclusion: SGLT2i significantly decreased the risk of cardiovascular events in KTRs with diabetes, particularly lowering the incidence of MI and death from cardiovascular causes. SGLT2i can be used to reduce the burden of cardiovascular disease in KTRs with diabetes., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

BACKGROUND According to the current guidelines for liver transplantation (LT) of brain-dead donors with hepatitis B or C virus (HBV or HCV) in Korea, grafts from hepatitis B surface antigen (HBsAg)(+) or HCV antibody (anti-HCV)(+) donors must be transplanted only to HBsAg(+) or anti-HCV(+) recipients, respectively. We aimed to determine the current status and outcomes of brain-dead donor LT with HBV or HCV in Korea. MATERIAL AND METHODS This retrospective observational study included all LTs from brain-dead donors in the Korean Organ Transplantation Registry between April 2014 and December 2020. According to donor hepatitis status, 24 HBV(+), 1 HCV(+), and 1010 HBV(-)/HCV(-) donors were included. RESULTS Baseline/final model for end-stage liver disease score (MELD) for HBV(+), HCV(+), and HBV(-)/HCV(-) were 22.4±9.3/27.8±7.8, 16/11, and 33.0±15.4/35.5±7.1, respectively. MELD score of HBV (+) were lower than those of HBV(-)/HCV(-) (P<0.01). Five-year graft and patient survival rates of HBV(+) and HBV(-)/HCV(-) recipients were 81.7%/85.6%, and 76.6%/76.7%, respectively (P=0.73 and P=0.038). One-year graft and patient survival rates of HCV (+) graft recipients were both 100%. CONCLUSIONS No differences in graft and patient survival rates between HBV(+) and HBV(-)/HCV(-) groups were observed. Although accumulating the results of transplants from HBV (+) or HCV(+) grafts to HBV(-) or HCV(-) recipients is not possible owing to domestic regulations, Korea should conditionally permit transplantations from HBV(+) or HCV(+) grafts to HBV(-) or HCV(-) recipients by considering the risks and benefits based on foreign studies. Thereafter, we can accumulate the data from Korea and analyze the outcomes.

Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-α, interleukin-1β, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed IκB phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200., (© 2024 The Authors. Xenotransplantation published by John Wiley & Sons Ltd.)

Introduction: Coronary artery calcification score (CACS) and abdominal aortic calcification score (AACS) are both well-established markers of vascular stiffness, and previous studies have shown that a higher CACS is a risk factor for chronic kidney disease (CKD) progression. However, the impact of pretransplant CACS and AACS on cardiovascular and renal outcomes in kidney transplant patients has not been established., Methods: We included 944 kidney transplant recipients from the KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) cohort and categorized them into three groups (low, medium, and high) according to baseline CACS (0, 0 < and ≤100, >100) and AACS (0, 1-4, >4). The low (0), medium (0 < and ≤ 100), and high (>100) CACS groups each consisted of 462, 213, and 225 patients, respectively. Similarly, the low (0), medium (1-4), and high (>4) AACS groups included 638, 159, and 147 patients, respectively. The primary outcome was the occurrence of cardiovascular events. The secondary outcomes were all-cause mortality and composite kidney outcomes, which comprised of >50% decline in the estimated glomerular filtration rate and graft loss. Cox regression analysis was used to investigate the association between baseline CACS/AACS and outcomes., Results: The high CACS group ( N = 462) faced a significantly higher risk for cardiovascular outcomes (adjusted hazard ratio [aHR], 5.97; 95% confidence interval [CI], 2.01-17.7) and all-cause mortality (aHR, 2.74; 95% CI, 1.27-5.92) compared to the low CACS group ( N = 225). Similarly, the high AACS group ( N = 638) had an elevated risk for cardiovascular outcomes (aHR, 2.38; 95% CI, 1.16-4.88). Furthermore, the addition of CACS to prediction models improved prediction indices for cardiovascular outcomes. However, the risk of renal outcomes did not differ among CACS or AACS groups., Conclusion: Pretransplant arterial calcification, characterized by high CACS or AACS, is an independent risk factor for cardiovascular outcomes and mortality in kidney transplant patients., Competing Interests: The authors of this manuscript have no conflicts of interest to disclose., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

In a semi-competing risks model in which a terminal event censors a non-terminal event but not vice versa, the conventional method can predict clinical outcomes by maximizing likelihood estimation. However, this method can produce unreliable or biased estimators when the number of events in the datasets is small. Specifically, parameter estimates may converge to infinity, or their standard errors can be very large. Moreover, terminal and non-terminal event times may be correlated, which can account for the frailty term. Here, we adapt the penalized likelihood with Firth's correction method for gamma frailty models with semi-competing risks data to reduce the bias caused by rare events. The proposed method is evaluated in terms of relative bias, mean squared error, standard error, and standard deviation compared to the conventional methods through simulation studies. The results of the proposed method are stable and robust even when data contain only a few events with the misspecification of the baseline hazard function. We also illustrate a real example with a multi-centre, patient-based cohort study to identify risk factors for chronic kidney disease progression or adverse clinical outcomes. This study will provide a better understanding of semi-competing risk data in which the number of specific diseases or events of interest is rare., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients., Methods: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT)., Results: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR., Conclusions: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan-Meier curve analysis (P < 0.001, log-rank test), with the highest incidence observed in the 4th quartile. Cox regression analysis indicated that, relative to the 1st quartile, the risk of 3-point MACE was significantly higher in the 3rd (adjusted hazard ratio 2.901, 95% confidence interval 1.009 to 8.341) and the 4th quartiles (adjusted hazard ratio 4.347, 95% confidence interval 1.410 to 13.395). In conclusion, elevated circulating OPG levels are associated with adverse cardiovascular outcomes in pre-dialysis CKD patients., (© 2024. The Author(s).)

Background: Immunoglobulin M (IgM) nephropathy (IgMN) is characterized by the IgM deposition in the kidney's mesangium. We assessed the impact of electron-dense deposits (EDDs) on IgMN and compared it to other kidney diseases., Methods: We enrolled 63 adult patients with IgMN who underwent renal biopsy from May 2003 to June 2017. We compared clinicopathological features of IgMN based on EDD presence; compared characteristics to 91 minimal change disease (MCD), 103 focal segmental glomerulosclerosis (FSGS), and 469 immunoglobulin A nephropathy (IgAN) patients. Renal events were defined as a >50% decrease in estimated glomerular filtration rate (eGFR), eGFR of <15 mL/min/1.73 m2, or end-stage renal disease development., Results: IgMN patients with EDDs had increased mesangial cellularity, matrix accumulation, prominent immunofluorescent staining, and more diffuse podocyte effacement than those without EDD. Clinical characteristics and renal outcomes did not differ significantly based on EDD presence. During 79.5 ± 58.8 months of follow-up, renal events developed in 46.2% and 46.0% of IgMN cases with and without EDD. IgMN (46.0%) and FSGS cases (40.8%) had similar frequencies of renal events and higher frequency than MCD (18.7%) or IgAN cases (26.4%). IgMN cases had more severe manifestations than MCD and IgAN; higher blood pressure, lower proteinuria, and eGFR levels at biopsy than MCD cases; higher blood pressure, proteinuria, frequency of acute kidney injury, and lower eGFR levels., Conclusion: Clinical characteristics of IgMN did not differ based on EDD presence. Therefore, IgMN should be defined based on IF findings. IgMN shared clinical characteristics with FSGS but had more severe than MCD and IgAN.

In this study, we propose an efficient field-free line (FFL) generator for mechanically driven FFL magnetic particle imaging (MPI) applications. The novel FFL generator comprises pairs of Halbach arrays and bar magnets. The proposed design generates high-gradient FFLs with low-mass permanent magnets, realizing fine spatial resolutions in MPI. We investigate the magnetic field generated using simulations and experiments. Our results show that the FFL generator yields a high gradient of 4.76 T/m at a cylindrical field of view of 30 mm diameter and a 70 mm open bore. A spatial resolution of less than 3.5 mm was obtained in the mechanically driven FFL-MPI.

Metformin is the primary treatment for type 2 diabetes mellitus (T2DM) due to its effectiveness in improving clinical outcomes in patients with preserved renal function, however, the evidence on the effectiveness of metformin in various renal functions is lacking. We performed a retrospective, multicenter, observational study used data of patients with T2DM obtained from three tertiary hospitals' databases. Patients given metformin within run-in periods and with at least one additional prescription formed the metformin cohort. A control cohort comprised those prescribed oral hypoglycemic agents other than metformin and never subsequently received a metformin prescription within observation period. For patients without diabetic nephropathy (DN), the outcomes included events of DN, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). After 1:1 propensity matching, 1994 individuals each were selected for the metformin and control cohorts among T2DM patients without baseline DN. The incidence rate ratios (IRR) for DN, MACEs, and MAKEs between cohorts were 1.06 (95% CI 0.96-1.17), 0.76 (0.64-0.92), and 0.45 (0.33-0.62), respectively. In cohorts with renal function of CKD 3A, 3B, and 4, summarized IRRs of MACEs and MAKEs were 0.70 (0.57-0.87) and 0.39 (0.35-0.43) in CKD 3A, 0.83 (0.74-0.93) and 0.44 (0.40-0.48) in CKD 3B, and 0.71 (0.60-0.85) and 0.45 (0.39-0.51) in CKD 4. Our research indicates that metformin use in T2DM patients across various renal functions consistently correlates with a decreased risk of overt DN, MACE, and MAKE., (© 2024. The Author(s).)

Background: According to the current Center for Korean Network for Organ Sharing guidelines for kidney transplantation from brain-dead donors with hepatitis B or C infection, organs from hepatitis B surface antigen-positive (HbsAg + ) or anti-hepatitis C virus-positive (HCV + ) donors can only be transplanted into HBsAg + or anti-HCV + recipients. We aimed to confirm the status and the outcomes of kidney transplantation from brain-dead donors with hepatitis B or C virus in Korea., Methods: This retrospective study included all kidney transplantations from brain-dead donors in the Korean Organ Transplantation Registry database between January 2015 and June 2020, divided into 3 groups according to donor hepatitis status. Finally, kidney transplantations from 80 HBV + , 12 HCV + , and 2013 HBV - /HCV - donors were included., Results: No statistically significant differences were observed in the recipient characteristics and the transplant outcomes except the waiting time (HBV + to HBV - /HCV - , P < .001; HCV + to HBV - /HCV - , P = .10; HBV + to HCV + P = .95). Five-year graft survival rates of the HBV + , HCV + , and HBV - /HCV - recipients were 95%, 83%, and 85%, respectively (HBV + to HCV + , P = .22; HCV + to HBV - /HCV - , P = .81; HBV + to HBV - /HCV - , P = .02). Five-year patient survival rates of the HBV + , HCV + , and HBV - /HCV - recipients were 95%, 100%, and 76%, respectively (HBV + to HCV + , P = .61; HCV + to HBV - /HCV - , P = .13; HBV + to HBV - /HCV - , P < .001)., Conclusion: HBV + /HCV + brain-dead donor kidney transplantation outcomes were comparable to HBV - /HCV - . South Korea should consider conditionally permitting transplantation from HBV + or HCV + donors to HBV - or HCV - recipients to accumulate new data and conduct further studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: The effect of routine ureteral stenting on postoperative hydronephrosis and percutaneous ureteral intervention in kidney transplant remains unknown. This study aimed to evaluate the effects of routine ureteral stenting on hydronephrosis and percutaneous ureteral intervention and the cost benefit of ureteral stenting in kidney transplant., Materials and Methods: We retrospectively analyzed patients who underwent kidney transplant at a tertiary institution between 2005 and 2021. We adopted a ureteral stentingprotocol in2017, anda comparisonwas performed with previous patients without stents., Results: In total, 539 patients underwent kidney transplant(271 with stents [51.3%], 268 without stents [49.7%]). Hydronephrosis was detected in 16 cases (5.9%) and 30 cases (11.2%) of groups with and without stents,respectively (P = .041). Among patients with hydronephrosis, the number of patients who underwent percutaneous ureteral intervention was significantly lower in the stent group than in the nostent group (1 [6.25%] vs 10 [33.33%]; P= .014).Twenty patients (3.71%) experienced major urologic complications (19 [7.1%] in the no-stent group, and 1 [0.4%] in the stent group; P = .001). No significant differences between the groups were shown in the incidence of urinary tract infections within 3 months of transplant (24 [8.9%] vs 22 [8.2%]; P = .846). No differences were shown between the groups in ureterovesical anastomosis time (24.4 vs 24.03 min; P = .699) or 1-year graft survival (97% vs 97.8%; P = .803). The healthcare cost was significantly lower in the stent group than in the no-stent group by $1702.05 ($15000.89 vs $16702.95; P < .001)., Conclusions: Routine ureteral stenting in kidney transplant significantly decreased the incidence of postoperative hydronephrosis and percutaneous ureteral intervention. Stenting did notlead to increased urinary tract infections and was cost-effective.

Background: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes., Methods: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow-up period., Results: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person-years of follow-up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person-years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause-specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60-0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13-1.64) for BP above both targets, compared with BP controlled within 2012 target only., Conclusion: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

Background: The 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine-based estimated glomerular filtration rate (eGFRcr) equation contains a race component that is not based on biology and may cause a bias in results. Therefore, the 2021 eGFRcr and creatinine-cystatin C-based eGFR (eGFRcr-cysC) equations were developed with no consideration of race. This study compared the cardiovascular event (CVE) and all-cause mortality and CVE combined predictability among the three eGFR equations in Korean chronic kidney disease (CKD) patients., Methods: This study included 2,207 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) index were used to compare the predictability of the study outcomes according to the 2009 eGFRcr, 2021 eGFRcr, and 2021 eGFRcr-cysC equations., Results: The overall prevalence of CVE and all-cause mortality were 9% and 7%, respectively. There was no difference in area under the curve of ROC for CVE and mortality and CVE combined among all three equations. Compared to the 2009 eGFRcr, both the 2021 eGFRcr (NRI, 0.013; 95% confidence interval [CI], - 0.002 to 0.028) and the eGFRcr-cysC (NRI, -0.001; 95% CI, -0.031 to 0.029) equations did not show improved CVE predictability. Similar findings were observed for mortality and CVE combined predictability with both the 2021 eGFRcr (NRI, -0.019; 95% CI, -0.039-0.000) and the eGFRcr-cysC (NRI, -0.002; 95% CI, -0.023 to 0.018)., Conclusion: The 2009 eGFRcr equation was not inferior to either the 2021 eGFRcr or eGFRcr-cysC equation in predicting CVE and the composite of mortality and CVE in Korean CKD patients.

A rod-shaped, motile, Gram-negative bacterial strain named DM-R-R2A-13 T was isolated from the plant Cannabis sativa L. 'Cheungsam'. The phylogenetic analysis of the 16S rRNA gene sequence revealed that strain DM-R-R2A-13 T belongs to the family Oxalobacteraceae and is closely related to members of the genus Massilia, with Massilia flava (97.58% sequence similarity) and Massilia armeniaca (97.37% sequence similarity) being the closest members. The digital DNA-DNA hybridization (dDDH) values between strain DM-R-R2A-13 T and Massilia flava CGMCC 1.10685 T and Massilia armeniaca ZMN-3 T were 22.2% and 23.3%, while the average nucleotide identity (ANI) values were 78.85% and 79.63%, respectively. The DNA G+C content was measured to be 64.6 mol%. Moreover, the bacterium was found to contain polyhydroxyalkanoate (PHA) granules based on transmission electron microscopy, indicating its potential to produce bioplastic. Genome annotation revealed the presence of PHA synthase genes (phaC, phaR, phaP, and phaZ), and the biopolymer was identified as poly-3-hydroxybutyrate (PHB) based on nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) analyses. Using maltose as a carbon source, the strain produced PHB of up to 58.06% of its dry cell weight. Based on the phenotypic, chemotaxonomic, and phylogenetic characteristics, it has been determined that DM-R-R2A-13 T represents a novel species belonging to the genus Massilia. As such, the name Massilia endophytica sp. nov. is proposed for this newly identified species. The type strain is DM-R-R2A-13 T (= KCTC 92072 T  = GDMCC 1.2920 T )., (© 2023. Springer Nature Limited.)

Transplantation of organs, cells, or tissues from one species to another, known as xenotransplantation, has the potential to alleviate organ donor shortages and enhance the success of organ transplantation. However, the possibility of immunological rejection by the recipient is one of the biggest difficulties associated with xenotransplantation. The creation of neutrophil extracellular traps (NETs), also known as NETosis, is hypothesized as a mechanism of rejection. Innovations in microfluidics and co-culturing techniques have provided access to several classes of microengineered model systems in experimental models, connecting animal research and traditional in vitro methods such as organoids, microphysiological systems, and organs-on-chip. To achieve this goal, we established a perfusable 3D Xeno vessel chip using a porcine aortic endothelial cell line and examined how NETs grow when isolated human and primate neutrophils were used. Neutrophils from both humans and monkeys displayed the usual NETosis phases, including nuclear decondensation, enlargement, and rounding of DNA, occupying the entire cytoplasm, and discharge of fragmented DNA after cell membrane rupture. Using confocal fluorescence imaging of DNA and citrullinated histone colocalization and DNA histone complex formation in supernatants from xeno vessel chips, we confirmed NETs generation by human and monkey neutrophils when cocultured in a xeno-vessel chip., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rationale & Objective: Metformin has been recommended for some patients with advanced chronic kidney disease. However, the value of metformin in kidney transplant recipients (KTRs) with pretransplant diabetes mellitus (DM) or posttransplant DM is uncertain. We investigated the clinical effects of metformin in KTRs., Study Design: Retrospective cohort study., Setting & Participants: A total of 1,995 KTRs with diabetes from 6 tertiary referral centers in the Republic of Korea., Exposure: Metformin usage was defined as the use of metformin for>90 days after kidney transplantation; 1,193 KTRs were metformin users, and 802 KTRs did not use metformin. Changing usage of metformin among those exposed for >90 days was also characterized., Outcome: Primary outcomes were all-cause mortality and death-censored graft failure (DCGF). Secondary outcomes were biopsy-proven acute rejection (BPAR) and lactic acidosis events., Analytical Approach: Survival analyses were conducted using multivariable Cox regression and competing risk analyses using Fine and Gray models. Changes in metformin use over time were modeled using a time-varying covariate. Metformin usage, mean daily dose, and hemoglobin A 1c (HbA 1c ) changes were considered in the landmark analysis to address time-varying confounding., Results: Metformin use was associated with a lower risk of DCGF (adjusted hazard ratio [AHR], 0.47 [95% CI, 0.23-0.96], P=0.038); there was no significant association with all-cause mortality (AHR, 0.94 [95% CI, 0.32-2.76], P=0.915) or BPAR (AHR 0.98 [95% CI, 0.62-1.54], P=0.942). In the subgroup analysis, metformin usage was associated with a reduced risk of all-cause mortality and a lower risk of DCGF for both pretransplantation DM and posttransplant DM groups. Metformin usage was associated with a lower risk of BPAR in the posttransplant DM group, although it was less effective in the pretransplantation DM group. There was no confirmed case of metformin-associated lactic acidosis (MALA) in the present cohort. A higher dose of metformin was correlated with lower risks of DCGF and BPAR., Limitations: Data on newer antidiabetic drugs such as SGLT2 inhibitors are limited, and there is potential limited generalizability to other populations., Conclusions: Metformin usage may benefit KTRs, as evidenced by its association with a reduced risk of DCGF and the absence of MALA events. Randomized controlled trials are needed to validate these observational findings., (Copyright © 2023. Published by Elsevier Inc.)

Background: Prevention and diagnosis of postcontrast acute kidney injury (AKI) after contrast-enhanced computed tomography is burdensome in outpatient department. We investigated whether an electronic alert system could improve prevention and diagnosis of postcontrast AKI., Methods: In March 2018, we launched an electronic alert system that automatically identifies patients with a baseline estimated glomerular filtration rate of &lt;45 mL/min/1.73 m2, provides a prescription of fluid regimen, and recommends a follow-up for serum creatinine measurement. Participants prescribed contrast-enhanced computed tomography at outpatient department before and after the launch of the system were categorized as historical and alert group, respectively. Propensity for the surveillance of postcontrast AKI was compared using logistic regression. Risks of AKI, admission, mortality, and renal replacement therapy were analyzed., Results: The historical and alert groups included 289 and 309 participants, respectively. The alert group was more likely to be men and take diuretics. The most frequent volume of prophylactic fluid in historical and alert group was 1,000 and 750 mL, respectively. Follow-up for AKI was more common in the alert group (adjusted odds ratio, 6.00; p &lt; 0.001). Among them, incidence of postcontrast AKI was not statistically different. The two groups did not differ in risks of admission, mortality, or renal replacement therapy., Conclusion: The electronic alert system could assist in the detection of high-risk patients, prevention with reduced fluid volume, and proper diagnosis of postcontrast AKI, while limiting the prescribing clinicians' burden. Whether the system can improve long-term outcomes remains unclear.

Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Son et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The risk of gadolinium (Gd)-based contrast agent (GBCA)-induced nephrogenic systemic fibrosis (NSF) in patients with end-stage renal disease (ESRD) and the efficacy of prophylactic hemodialysis (HD) for protection against NSF are not well understood or summarized in the literature., Purpose: To determine the risk for NSF related to frequency and time per dialysis session after Gd-magnetic resonance imaging (MRI) by emphasizing the safety of Gd-MRI in patients with ESRD., Material and Methods: This retrospective observational study identified all GBCA injections for MRI examinations performed at two tertiary referral hospitals between 2005 and 2020. All clinical data, including dialysis records and medical history, were investigated for each patient through 2021. The end of follow-up coincided with the last hospital visit., Results: Overall, 1129 patients with ESRD underwent 1461 Gd-MRI scans (41.5% gadoterate, 39.4% gadobutrol, and 7.7% gadoxetate); a total of 958 patients with 1229 (84.1%) examinations underwent HD on the day of the MRI study, within 2.1 ± 2.0 h (range = 0.2-15.7 h) immediately after Gd exposure. In 53.4% of scans, frequent HD had been performed urgently and then twice more on consecutive days to prophylactically avoid NSF. No cases of NSF were identified during the follow-up period (mean = 81.7 ± 50.5 months) regardless of dose of HD., Conclusion: No cases of NSF were reported in 1461 Gd-MRI examinations of 1129 inpatients with ESRD on HD. Our findings support the lack of benefit of frequent prophylactic HD being performed urgently within 4 h of the receipt of GBCA.

Background: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD)., Methods: This study included 2,149 patients with CKD G1-G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT)., Results: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of &lt;60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922-0.960) and eGFRcr (0.941; 95% CI, 0.922-0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW)., Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.

Background: Sex disparity is prevalent in organ transplantations worldwide. This study aimed to understand sex disparities in dialysis and kidney transplantation in Korea over the last 20 years., Methods: Data for incident dialysis, waiting list registration, and donors and recipients were retrospectively collected between January 2000 and December 2020 from the Korean Society of Nephrology end-stage renal disease registry and the database of the Korean Network for Organ Sharing. Data regarding the proportion of females for dialysis, waiting list, and kidney transplantation donors or recipients were analyzed using linear regression analysis., Results: The average proportion of females on dialysis over the past 20 years was 40.5%. The proportion of females on dialysis was 42.8% in 2000, and decreased to 38.2% in 2020, showing a decreasing trend. The average proportion of women on the waiting list was 38.4%, which was lower than that for dialysis. The average proportion of female recipients in living donor kidney transplantation and female living donors were 40.1% and 53.2%, respectively. The overall proportion of female donors in living donor kidney transplantation showed an increasing trend. However, there was no change in the proportion of female recipients in living donor kidney transplantation., Conclusion: Sex disparities in organ transplantation exist, including an increasing trend of female donors in living donor kidney transplantation. Further studies are needed to identify the biological and socioeconomic factors involved to resolve these disparities.

Agastache rugosa (popularly known as Korean mint) belongs to the Lamiaceae family and comprises 22 species of perennial aromatic medicinal species native to East Asian countries, such as Korea, Taiwan, Japan, and China. A. rugosa contains many phenolic compounds that exhibit pharmacological and physiological activities, including antioxidant, anticancer, antiviral, antifungal, and antibacterial activities. The highest concentrations of rosmarinic acid and its isomers have been reported in the roots of A. rugosa . In this in vitro study, hairy roots of A. rugosa were obtained and the carbohydrates (sorbitol, mannitol, glucose, maltose, galactose, mannose, and sucrose) were evaluated to determine those that were optimal for rosmarinic acid production and hairy root growth. Antioxidant and antibacterial activities of extracts of A. rugosa were also assessed. The best carbon source for A . rugosa hairy root cultures was sucrose, considering biomass productivity (0.460 ± 0.034 mg/30 mL), rosmarinic acid production (7.656 ± 0.407 mg/g dry weight), and total phenolic content (12.714 ± 0.202 mg/g gallic acid equivalent). Antioxidant and antimicrobial activities were displayed by A . rugosa hairy roots cultured in liquid medium supplemented with 100 mM sucrose. Twenty-five bacterial strains, including multidrug-resistant bacteria and one pathogenic yeast strain, were used for antimicrobial screening of A . rugosa hairy roots. The hairy root extracts displayed antibacterial activity against Micrococcus luteus (KCTC 3063) and Bacillus cereus (KCTC 3624). The inhibition of these bacteria was greater using A . rugosa hairy roots with the highest levels of phenolic compounds cultured in the presence of sucrose, compared to hairy roots with the lowest levels of phenolic compounds cultured in the presence of fructose. Considering hairy root biomass, phenolic compound production, and antibacterial activity, sucrose is the best carbon source for A . rugosa hairy root cultures.

Competing Interests: The authors declare no conflicts of interest.

Background: Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition., Methods: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis., Results: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of &lt;60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p &lt; 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001)., Conclusion: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

When plants are exposed to stressful conditions, they modulate their nutrient balance by regulating their primary and secondary metabolisms to adapt. In this study, changes in primary and secondary metabolites elicited by chilling stress treatment and the effects of treatment duration were examined in roots of Scutellaria baicalensis ( S. baicalensis ) plantlets. The concentrations of most sugars (maltose, glucose, sucrose, and fructose) and of several amino acids (proline and GABA), which are crucial regarding plant defense mechanisms, increased with increasing duration of chilling stress. Furthermore, salicylic acid levels increased after two-day chilling treatments, which may enhance plant tolerance to cold temperatures. The concentrations of flavones (baicalin, baicalein, and wogonin) increased during chilling stress, and those of phenolic acids (ferulic acid and sinapic acid) increased after two-day chilling treatments. The concentrations of these flavones were positively correlated with sucrose levels which acted as energy sources.

Aceclofenac controlled-release (CR) is a once-a-day tablet with 200 mg of aceclofenac, and is bioequivalent to conventional aceclofenac. However, its safety in humans has not been well studied in Korea. Therefore, we aimed to evaluate the overall incidence and patterns of adverse events (AEs), the effectiveness of aceclofenac CR, and the differences in incidence rates of the AEs based on each patient's baseline charateristics. This study was conducted on patients receiving aceclofenac CR in clinical practice at each investigational institution to treat musculoskeletal pain and inflammation. The subjects were administered one tablet of aceclofenac CR (200 mg once-a-day) and were observed for 4 weeks post-administration. Factors affecting the occurrence of AEs were evaluated, and the Visual Analogue Scale (VAS) was used to measure the pain intensity. Among 14,543 subjects, the incidence rate of AEs was 0.86%, and that of adverse drug reactions was 0.74%. No serious AEs and unexpected adverse drug reactions were monitored. The incidence rates of AEs were significantly higher in females, inpatient treatment, individuals with concurrent disorders, and those receiving concomitant medications, respectively (all P < 0.05). Four weeks post-using aceclofenac CR, the mean changes in VAS was significantly decreased compared to prior administration. The overall clinical efficacy rate was 91.63%. This study confirmed that no severe adverse reactions were observed for aceclofenac CR exceeding those previously reported for safety results of conventional formulation of this drug in routine clinical practice settings. The use of aceclofenac CR might not violate the previously reported information on the safety and effectiveness of aceclofenac., (© 2022. The Author(s).)

Purpose: Acute kidney injury (AKI) has shown an increasingly common occurrence among hospitalized patients worldwide. We determined the incidence and compared the short- and long-term outcomes of all stages of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and identified predictors for such outcomes., Materials and Methods: This observational, single-center, retrospective study identified patients admitted between January 2013 and December 2013 who developed CA-AKI or HA-AKI. Short- and long-term patient and renal outcomes were analyzed., Results: AKI incidence was 14.3% (1882, CA-AKI 4.8% and HA-AKI 9.5%). The highest 30-day and 1-year mortality were recorded in the CA-AKI group. Thirty-day mortality rate was 11.4% in CA-AKI group and 5.7% in HA-AKI group ( p <0.001). One-year mortality rates were 20.1% and 13.3%, respectively ( p <0.001). More CA-AKI patients developed kidney failure with replacement therapy within 1 year (27, 4.3% vs. 18, 1.4% respectively, p <0.001)., Conclusion: In conclusion, patients with CA-AKI had worse short- and long-term outcomes compared to HA-AKI patients. AKI severity and discharge serum creatinine were significant independent predictors of 30-day and 1-year mortality., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

A Gram-negative, aerobic, rod-shaped bacterium, designated DM2-R-LB4 T was isolated from Cannabis sativa L. 'Cheungsam' in Andong, Republic of Korea. The strain DM2-R-LB4 T grew at temperatures of 15-45 °C (optimum, 30-37 °C), pH of 5.5-9 (optimum, 8.0), and 0-2 % (w/v) NaCl concentration (optimum, 0%). Phylogenetic analyses based on the 16S rRNA gene sequences revealed that strain DM2-R-LB4 T is related to species of the genus Sphingomonas , and shared 97.8 and 97.5% similarity to Sphingomonas kyenggiensis KCTC 42244 T and Sphingomonas leidyi DSM 4733 T , respectively. The DNA G+C content was 67.9 mol% and genome analysis of the strain DM2-R-LB4 T revealed that the genome size was 4 386 171 bp and contained 4 009 predicted protein-coding genes. The average nucleotide identity (ANI) values between strain DM2-R-LB4 T and S. kyenggiensis KCTC 42244 T , and S. leidyi DSM 4733 T was 76.8 and 76.7 %, respectively, while the values of digital DNA-DNA hybridization (dDDH) were 20.7 and 20.6 %, respectively. C 14 : 0 2-OH, C 16 : 0 , and summed feature 8 (C 18 : 1  ω6c and/or C 18 : 1  ω7c) were the major fatty acids (>10 %) in the strain DM2-R-LB4 T . The polar lipids comprised diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), sphingoglycolipid (SGL), glycolipid (GL), phospholipid (PL), and two unidentified polar lipids (L1 and L2). Ubiquinone-10 (Q-10) was the only respiratory quinone. The polyamine pattern was found to contain homospermidine, putrescine, and spermidine. The results of phylogenetic anlayses, polyphasic studies, revealed that strain DM2-R-LB4 T represents a novel species of the genus Sphingomonas , for which the name Sphingomonas cannabina sp. nov., is proposed. The type strain is DM2-R-LB4 T (=KCTC 92075 T = GDMCC 1.3018 T ).

Background: Public Data Commons (PDC) have been highlighted in the scientific literature for their capacity to collect and harmonize big data. On the other hand, local data commons (LDC), located within an institution or organization, have been underrepresented in the scientific literature, even though they are a critical part of research infrastructure. Being closest to the sources of data, LDCs provide the ability to collect and maintain the most up-to-date, high-quality data within an organization, closest to the sources of the data. As a data provider, LDCs have many challenges in both collecting and standardizing data, moreover, as a consumer of PDC, they face problems of data harmonization stemming from the monolithic harmonization pipeline designs commonly adapted by many PDCs. Unfortunately, existing guidelines and resources for building and maintaining data commons exclusively focus on PDC and provide very little information on LDC., Results: This article focuses on four important observations. First, there are three different types of LDC service models that are defined based on their roles and requirements. These can be used as guidelines for building new LDC or enhancing the services of existing LDC. Second, the seven core services of LDC are discussed, including cohort identification and facilitation of genomic sequencing, the management of molecular reports and associated infrastructure, quality control, data harmonization, data integration, data sharing, and data access control. Third, instead of commonly developed monolithic systems, we propose a new data sharing method for data harmonization that combines both divide-and-conquer and bottom-up approaches. Finally, an end-to-end LDC implementation is introduced with real-world examples., Conclusions: Although LDCs are an optimal place to identify and address data quality issues, they have traditionally been relegated to the role of passive data provider for much larger PDC. Indeed, many LDCs limit their functions to only conducting routine data storage and transmission tasks due to a lack of information on how to design, develop, and improve their services using limited resources. We hope that this work will be the first small step in raising awareness among the LDCs of their expanded utility and to publicize to a wider audience the importance of LDC., (© 2022. The Author(s).)

Phytic acid (PA) acts as an antinutrient substance in cereal grains, disturbing the bioavailability of micronutrients, such as iron and zinc, in humans, causing malnutrition. GmIPK1 encodes the inositol 1,3,4,5,6-penta kis phosphate 2-kinase enzyme, which converts myo -inopsitol-1,3,4,5,6-penta kis phosphate (IP 5 ) to myo -inositol-1,2,3,4,5,6-hexakisphosphate (IP 6 ) in soybean ( Glycine max L.). In this study, for developing soybean with low PA levels, we attempted to edit the GmIPK1 gene using the CRISPR/ Cas9 system to introduce mutations into the GmIPK1 gene with guide RNAs in soybean (cv. Kwangankong). The GmIPK1 gene was disrupted using the CRISPR/Cas9 system, with sgRNA-1 and sgRNA-4 targeting the second and third exon, respectively. Several soybean Gmipk1 gene-edited lines were obtained in the T 0 generation at editing frequencies of 0.1-84.3%. Sequencing analysis revealed various indel patterns with the deletion of 1-9 nucleotides and insertions of 1 nucleotide in several soybean lines (T 0 ). Finally, we confirmed two sgRNA-4 Gmipk1 gene-edited homozygote soybean T 1 plants (line #21-2: 5 bp deletion; line #21-3: 1 bp insertion) by PPT leaf coating assay and PCR analysis. Analysis of soybean Gmipk1 gene-edited lines indicated a reduction in PA content in soybean T 2 seeds but did not show any defects in plant growth and seed development.

Background: Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension., Methods: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of &lt;90 mmHg) with intervention over the 3 months following enrollment. Logistic regression models including each parameter related to sarcopenia were compared with a clinical model., Results: Patients with a low ratio of skeletal muscle mass to dry body weight (SMM/WT) had a higher rate of intradialytic hypotension (40.7%). Most low-SMM/WT patients were female, obese, diabetic, and had a lower handgrip strength compared with the other patients. In the high-SMM/WT group, the risk of intradialytic hypotension was lower, with an odds ratio of 0.08 (95% confidence interval [CI], 0.02-0.28) and adjusted odds ratio of 0.06 (95% CI, 0.01-0.29)., Conclusion: Measurement and maintenance of skeletal muscle can help prevent intradialytic hypotension in frail patients undergoing hemodialysis.

Background: The efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been investigated in kidney transplant recipients (KTRs) with diabetes. We evaluated the impact of SGLT2i in a multicenter cohort of diabetic KTRs., Methods: A total of 2083 KTRs with diabetes were enrolled from 6 transplant centers in Korea. Among them, 226 (10.8%) patients were prescribed SGLT2i for >90 d. The primary outcome was a composite outcome of all-cause mortality, death-censored graft failure (DCGF), and serum creatinine doubling. An acute dip in estimated glomerular filtration rate (eGFR) over 10% was surveyed after SGLT2i use., Results: During the mean follow-up of 62.9 ± 42.2 mo, the SGLT2i group had a lower risk of primary composite outcome than the control group in the multivariate and propensity score-matched models (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78; P = 0.006 and adjusted hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P = 0.013, respectively). Multivariate analyses consistently showed a decreased risk of DCGF and serum creatinine doubling in the SGLT2i group. The overall eGFR remained stable without the initial dip after SGLT2i use. A minority (15.6%) of the SGLT2i users showed acute eGFR dip during the first month, but the eGFR recovered thereafter. The risk factors for the eGFR dip were time from transplantation to SGLT2i usage and mean tacrolimus trough level., Conclusions: SGLT2i improved a composite of all-cause mortality, DCGF, or serum creatinine doubling in KTRs. SGLT2i can be used safely and have beneficial effects on preserving graft function in diabetic KTRs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)