Background: The heterogeneity of chronic kidney disease (CKD) and fragmented analysis methods hinder the precise identification of novel biomarkers. We addressed this challenge using two independent cohorts to integrate genomics and metabolomics, aiming to identify cause-specific biomarkers for CKD in the Korean population. Methods: A longitudinal genome-wide association study using the Cox proportional hazards model was conducted using the Ansan and Ansung cohort. To validate these genomic biomarkers and integrate them with plasma metabolomics biomarkers, we utilized a hospital-based biopsy cohort to identify cause-specific CKD biomarkers. Within the biopsy cohort, we analyzed four disease subsets, including type 2 diabetic kidney disease (DKD), hypertensive nephropathy (HN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN), and compared them with healthy individuals. Significant single nucleotide polymorphisms(SNPs) and metabolites for each CKD subset were identified through logistic regression and correlation-based network analyses. Subsequently, we analyzed the risk of disease progression associated with the identified pairs. Results: A total of 448 variants associated with CKD occurrence were identified, with significant differences in several genetic variants and metabolites observed among patients with DKD, HN, IgAN, and MN compared to healthy individuals. Among 36 SNP-metabolite pairs, those involing FOXB1 and ZFP42 were associated with DKD, whereas pairs involving MMRN1 and SYNJ2 were linked to MN. Notably, the rs1025170 variant in FOXB1 and tyrosine pair was correlated with DKD progression. Conclusion Integrating genomics and metabolomics across independent cohorts enables the discovery of cause-specific biomarkers for the occurrence and progression of CKD in the Korean population.

Background: Intradialytic hypotension (IDH) is a critical complication related to worse outcomes in patients undergoing maintenance hemodialysis. Herein, we addressed the impact of IDH on mortality and other outcomes in patients with severe acute kidney injury (AKI) requiring intermittent hemodialysis. Methods: We retrospectively reviewed 1,009 patients who underwent intermittent hemodialysis due to severe AKI. IDH was defined as either dialysis discontinuation due to hemodynamic instability or a decrease in systolic blood pressure (BP) of ≥30 mmHg, with or without a nadir systolic BP of <90 mmHg during the first session. The primary outcome was all-cause mortality, and transfer to the intensive care unit (ICU) due to unstable status was additionally analyzed. Hazard ratios (HRs) of outcomes were calculated using a Cox regression model after adjusting for multiple variables. Risk factors for IDH were evaluated using a logistic regression model. Results: IDH occurred in 449 patients (44.5%) during the first hemodialysis session. Patients with IDH had a higher mortality rate than those without IDH (40% vs. 23%; HR, 1.30; 95% confidence interval [CI], 1.02–1.65). The rate of ICU transfer was higher in patients experiencing IDH than in those without IDH (17% vs. 11%; HR, 1.43; 95% CI, 1.02–2.02). Factors such as old age, high BP and pulse rate, active malignancy, cirrhosis, and hypoalbuminemia were associated with an increased risk of IDH episodes. Conclusion The occurrence of IDH is associated with worse outcomes in patients with AKI requiring intermittent hemodialysis. Therefore, careful monitoring and early intervention of IDH may be necessary in this patient subset.

Cardiovascular disease is an important risk factor for mortality among kidney transplant recipients. In this study, we aimed to investigate the association between cardiovascular risk score at kidney transplantation and long-term outcomes of patients. Methods: In this prospective, observational cohort study, we enrolled kidney transplant recipients who participated in the Korean Organ Transplantation Registry and underwent transplantation between April 2014 and December 2019. The cardiovascular risk status of kidney transplant recipients was assessed using the Framingham risk score. All-cause mortality, major adverse cardiovascular events, allograft failure, estimated glomerular filtration rates (eGFRs), and composite outcomes were evaluated after kidney transplantation. Results: Of the 4,682 kidney transplant recipients, 96 died during 30.7 ± 19.1 months of follow-up. The Kaplan-Meier survival analysis results showed that high Framingham risk scores were associated with all-cause mortality, major adverse cardiovascular events, and composite outcomes. According to the multivariable Cox analysis, high Framingham risk scores were associated with an increased risk of mortality (hazard ratio [HR], 3.20; 95% confidence interval [CI], 1.30–7.91), major adverse cardiovascular events (HR, 8.43; 95% CI, 2.41–29.52), and composite outcomes (HR, 2.05; 95% CI, 1.19–3.46). The eGFRs after transplantation were significantly higher among patients in the low Framingham risk score group (p < 0.001). However, Framingham risk scores were not associated with graft loss or rapid decline in eGFRs. Conclusion: The Framingham risk score is a useful indicator of cardiovascular events, mortality, and kidney function after kidney transplantation.

Background: We aimed to investigate the characteristics of pediatric ulcerative colitis (UC) at diagnosis in Korea. Methods: This was a multicenter, registry-based, inception cohort study conducted in Korea between 2021 and 2023. Children and adolescents newly diagnosed with UC < 18 years were included. Baseline clinicodemographics, results from laboratory, endoscopic exams, and Paris classification factors were collected, and associations between factors at diagnosis were investigated. Results: A total 205 patients with UC were included. Male-to-female ratio was 1.59:1, and the median age at diagnosis was 14.7 years (interquartile range 11.9–16.2). Disease extent of E1 comprised 12.2% (25/205), E2 24.9% (51/205), E3 11.2% (23/205), and E4 51.7% (106/205) of the patients. S1 comprised 13.7% (28/205) of the patients. The proportion of patients with a disease severity of S1 was significantly higher in patients with E4 compared to the other groups (E1: 0% vs. E2: 2% vs. E3: 0% vs. E4: 24.5%, P < 0.001). Significant differences between disease extent groups were also observed in Pediatric Ulcerative Colitis Activity Index (median 25 vs. 35 vs. 40 vs. 45, respectively, P < 0.001), hemoglobin (median 13.5 vs.13.2 vs. 11.6 vs. 11.4 g/dL, respectively, P < 0.001), platelet count (median 301 vs. 324 vs. 372 vs. 377 × 103 /μL, respectively, P = 0.001), C-reactive protein (median 0.05 vs. 0.10 vs. 0.17 vs. 0.38 mg/dL, respectively, P < 0.001), and Ulcerative Colitis Endoscopic Index of Severity (median 4 vs. 4 vs. 4 vs. 5, respectively, P = 0.006). No significant differences were observed in factors between groups divided according to sex and diagnosis age. Conclusion This study represents the largest multicenter pediatric inflammatory bowel disease cohort in Korea. Disease severity was associated with disease extent in pediatric patients with UC at diagnosis.

Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. Methods: This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. Results: The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01–1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Conclusion: Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.

Background: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000–5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. Conclusions Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.Level of evidence: IV.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Background: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000–5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. Conclusions Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.Level of evidence: IV.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Objective: This study aimed to empirically evaluate the effectiveness of chronic disease management services utilizing ICT for patients with chronic illnesses. Methods: From May to December, 2023, 452 people who were diagnosed with hypertension and diabetes at 9 participating public health centers were provided with customized health care services for 24 weeks, and 15 performance indicators were analyzed to evaluate their effectiveness. Results: Health behavior indicators and health risk factors decreased before and after participation in the project, blood pressure control rate, hypertension and diabetes management rate, medication compliance, weight, BMI, BP, WC, FBG, and HDL-cholesterol improved(p<0.001).Service factors that influence the improvement of health behaviors included the number of activity monitor transmissions(p=0.049), confirmed concentrated consultations on physical activity(p=0.003) and nutrition(p=0.005), and the adherence to medication missions for hypertension(p=0.020).As for service factors influencing chronic disease management, the improvement in blood pressure regulation rate was due to the number of times the blood pressure monitor was linked(p=0.004), and the number of confirmed intensive consultations on physical activity(p=0.026), and nutrition(p=0.049); the improvement in hypertension control rate was due to the number of times the activity monitor and blood pressure monitor were linked(p<0.001), and the number of hypertension medication missions carried out (p=0.004); and the improvement in diabetes control rate was due to the number of times the blood pressure monitor(p=0.022) and blood sugar system were linked(p=0.017). Conclusion Although this study has limitations as a comparative study before and after the service, it has proved that chronic disease management using ICT has a positive effect on improvement of health behavior indicator, reduction of health risk factors, hypertension, diabetes management index, weight, BMI, TG, BP, FBG improvement.