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.

This study aimed to determine the association between trajectories of obesity status and prediabetes reversion to normoglycemia or progression to diabetes. The study included 14,452 participants from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort who continuously had prediabetes glycemic status during the index period (2002-2008), definedby their fasting plasma glucose. The exposure of the study was the trajectories of obesity (defined by body mass index ≥ 25 kg/m 2 ) generated using latent class growth analysis. The outcomes were reversion to normoglycemia or progression to diabetes, whichever occurred first during the follow-up period (2009-2016). The association between trajectories and changes in prediabetes status were examined using cause-specific hazard regression by obtaining the hazard ratio (HR) with a 95% CI. We identified three distinct trajectories which were “Stable obese”, “Stable non-obese” and “Obese to non-obese”. After a median follow-up of 2years, 51.99% of participants had their glycemic status back to normoglycemia and 32.17% developed diabetes. Compared with participants in the “Stable obese” group, those in “Stable non-obese” and “Obese to non-obese” groups were more likely to have reversion to normoglycemia (HR with a 95% CI = 1.30 [1.23-1.37] and 1.15 [1.07-1.24], respectively) and lower risk of developingdiabetes (0.78 [0.73-0.84] and 0.90 [0.82-0.98], respectively). The findings suggest that maintaining or achieving a non-obese sta-tus is linked to higher reversion to normoglycemia as well as lower risks of developing diabetes.

OBJECTIVES: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 United States adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in Korea and its association with demographic and socioeconomic status (SES). METHODS: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, gender, and SES factors. RESULTS: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7 to 25.8), stage 1 (19.3%; 95% CI, 18.9 to 19.7), stage 2 (51.6%; 95% CI, 51.1 to 52.2), and stages 3-4 (3.9%; 95% CI, 3.7 to 4.0). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income. CONCLUSIONS About 3 out of 4 Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

OBJECTIVES: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 United States adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in Korea and its association with demographic and socioeconomic status (SES). METHODS: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, gender, and SES factors. RESULTS: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7 to 25.8), stage 1 (19.3%; 95% CI, 18.9 to 19.7), stage 2 (51.6%; 95% CI, 51.1 to 52.2), and stages 3-4 (3.9%; 95% CI, 3.7 to 4.0). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income. CONCLUSIONS About 3 out of 4 Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

OBJECTIVES: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 United States adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in Korea and its association with demographic and socioeconomic status (SES). METHODS: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, gender, and SES factors. RESULTS: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7 to 25.8), stage 1 (19.3%; 95% CI, 18.9 to 19.7), stage 2 (51.6%; 95% CI, 51.1 to 52.2), and stages 3-4 (3.9%; 95% CI, 3.7 to 4.0). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income. CONCLUSIONS About 3 out of 4 Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

OBJECTIVES: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 United States adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in Korea and its association with demographic and socioeconomic status (SES). METHODS: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, gender, and SES factors. RESULTS: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7 to 25.8), stage 1 (19.3%; 95% CI, 18.9 to 19.7), stage 2 (51.6%; 95% CI, 51.1 to 52.2), and stages 3-4 (3.9%; 95% CI, 3.7 to 4.0). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income. CONCLUSIONS About 3 out of 4 Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.