Findings from the KNOW-CKD Study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression.

Time-in-target range (TTR) of systolic blood pressure (SBP) is determined by the proportion of time during which SBP remains within a defined optimal range. TTR has emerged as a useful metric for assessing SBP control over time. However, it is uncertain if SBP-TTR can predict the progression of chronic kidney disease (CKD). Here, we investigated the association between SBP-TTR during the first year of enrollment and CKD progression among 1758 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). Baseline median estimated glomerular filtration rate (eGFR) was 51.7 ml/min per 1.73 m2. Participants were categorized into four SBP-TTR groups (0%, 1-50%, 51-99%, and 100%). The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of kidney replacement therapy. During the follow-up period (9212 person-years over a median 5.4 years), the composite outcome occurred in 710 participants. In the multivariate cause-specific hazard model, a one-standard deviation increase in SBP-TTR was associated with an 11% lower risk of the composite outcome with hazard ratio, 0.89 (95% confidence interval, 0.82-0.97). Additionally, compared to patients with SBP-TTR 0%, the respective hazard ratios for those with SBP-TTR 1-50%, 51-99%, and 100% were 0.85 (0.68-1.07), 0.76 (0.60-0.96), and 0.72 (0.55-0.94), and the respective corresponding slopes of eGFR decline were -3.17 (-3.66 to -2.69), -3.02 (-3.35 to -2.68), -2.62 (-2.89 to - 2.36), and -2.33 (-2.62 to -2.04) ml/min/1.73 m2. Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

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.

Coronary artery calcium and risk of chronic kidney disease in young and middle-aged adults.

BACKGROUND: The role of the coronary artery calcium score (CACS) in incident chronic kidney disease (CKD) in asymptomatic young populations remains unclear. The aim of this study was to evaluate the association between CACSs and CKD development in adults. METHODS: A cohort study of 113 171 Korean adults (mean age 40.6 years) without CKD and proteinuria at baseline who underwent a cardiac tomography estimation of CACSs during health screening examinations was performed (median follow-up 4.2 years). The outcome was CKD, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and/or the presence of proteinuria. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were estimated using Cox proportional hazards regression analyses. RESULTS: A higher CACS was moderately associated with an increased risk of CKD in a dose-dependent manner. The multivariable-adjusted HRs for CKD comparing CACSs 1-100, 101-300 and >300 with a CACS of 0 were 1.15 (95% CI 1.05-1.25), 1.37 (95% CI 1.13-1.66) and 1.71 (95% CI 1.32-2.22), respectively (P for trend <.001). When CKD was defined using low eGFR and proteinuria separately, corresponding HRs for low eGFR were 1.31 (95% CI 1.05-1.62), 1.41 (95% CI 0.95-2.11) and 1.86 (95% CI 1.16-3.00), respectively (P for trend = .001), while the HRs for proteinuria were 1.11 (95% CI 1.02-1.21), 1.32 (95% CI 1.07-1.64) and 1.57 (95% CI 1.16-2.12), respectively. CONCLUSIONS: A higher CACS was progressively associated with an increased risk of CKD, even at low CACSs. Individuals with a CACS >0 appear to have an increased risk of CKD and may benefit from preventive measures to reduce CKD risk.

Effect of low-density lipoprotein level and mortality in older incident statin-naïve hemodialysis patients.

BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Measured sodium excretion is associated with CKD progression: results from the KNOW-CKD study.

BACKGROUND: Diet is a modifiable factor of chronic kidney disease (CKD) progression. However, the effect of dietary salt intake on CKD progression remains unclear. Therefore, we analyzed the effect of dietary salt intake on renal outcome in Korean patients with CKD. METHODS: We measured 24-h urinary sodium (Na) excretion as a marker of dietary salt intake in the prospective, multi-center, longitudinal KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD). Data were analyzed from CKD patients at Stages G3a to G5 (n = 1254). We investigated the association between dietary salt intake and CKD progression. Patients were divided into four quartiles of dietary salt intake, which was assessed using measured 24-h urinary Na excretion. The study endpoint was composite renal outcome, which was defined as either halving the estimated glomerular filtration rate or developing end-stage renal disease. RESULTS: During a median (interquartile range) follow-up of 4.3 (2.8-5.8) years, 480 (38.7%) patients developed the composite renal event. Compared with the reference group (Q2, urinary Na excretion: 104.2 ≤ Na excretion < 145.1 mEq/day), the highest quartile of measured 24-h urinary Na excretion was associated with risk of composite renal outcome [Q4, urinary Na excretion ≥192.9 mEq/day, hazard ratio 1.8 (95% confidence interval 1.12-2.88); P = 0.015] in a multivariable hazards model. Subgroup analyses showed that high-salt intake was particularly associated with a higher risk of composite renal outcome in women, in patients <60 years of age, in those with uncontrolled hypertension and in those with obesity. CONCLUSIONS: High salt intake was associated with increased risk of progression in CKD.

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

RATIONALE & OBJECTIVE: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. EXPOSURES: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). OUTCOME: Nephrolithiasis ascertained using abdominal ultrasound. ANALYTICAL APPROACH: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. RESULTS: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. LIMITATIONS: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. CONCLUSIONS: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.

Metabolically healthy and unhealthy obesity phenotypes and risk of renal stone: a cohort study.

BACKGROUND/OBJECTIVES: Although obesity is considered an independent risk factor of nephrolithiasis, little is known about the effect of obesity on nephrolithiasis according to metabolic health status. We investigated the association between body mass index (BMI) category and the incidence of nephrolithiasis in metabolically healthy and unhealthy individuals. SUBJECTS/METHODS: The cohort consisted of 270,190 Korean adults free of nephrolithiasis at baseline, who were followed-up annually or biennially for a median of 4.1 years. Nephrolithiasis were determined based on ultrasonographic findings. Being metabolically healthy was defined as not having any metabolic syndrome component. A parametric Cox model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During 1,415,523.0 person-years of follow-up, 13,450 participants developed nephrolithiasis (incidence rate, 9.5 per 1000 person-years). Obesity was positively associated with an increased risk of incident nephrolithiasis in dose-response manner, but the association was stronger in metabolically healthy individuals. Among metabolically healthy individuals, the multivariable-adjusted HRs (95% CIs) for incident nephrolithiasis comparing BMIs 23-24.9, 25-29.9, and ≥30 with a BMI of 18.5-22.9 kg/m2 as the reference were 1.02 (0.95-1.10), 1.12 (1.03-1.22), and 1.72 (1.21-2.44), respectively, whereas corresponding HRs (95% CIs) in metabolically unhealthy individuals were 1.10 (1.04-1.17), 1.27 (1.20-1.34), and 1.36 (1.22-1.51), respectively. The association between obesity and incident nephrolithiasis was stronger in men and current smokers. CONCLUSIONS: Obesity was associated with a higher incidence of nephrolithiasis in both metabolically healthy and unhealthy individuals, indicating obesity per se as an independent risk factor for nephrolithiasis.

eGFR and coronary artery calcification in chronic kidney disease.

BACKGROUND: The independent association between eGFR and coronary artery calcification (CAC) is complex and not clear. The aim of this study was to investigate the relationship between eGFR calculated from different equations and CAC in predialysis CKD patients in Korea. METHODS: In this cross-sectional study, we analysed 1533 patients from the KNOW-CKD cohort. eGFR was calculated by a four-variable MDRD equation (eGFRMDRD ), CKD-EPI creatinine equations (eGFRCr ), CKD-EPI cystatin C equation (eGFRCys ) and CKD-EPI creatinine-cystatin equation (eGFRCrCys ). Participants were divided into eGFR categories (<30, 30-59, 60-89, ≥90 mL/min/1.73 m2 ). CACS (coronary artery calcium score) was measured using cardiac computed tomography. CAC was defined as CACS >100. RESULTS: Coronary artery calcification was found in 334 (21.8%) patients and was more prevalent in the lower eGFR groups (P < 0.001). In multivariate Tobit regression, CACS increased gradually as eGFRCrCys decreased (P for trend = 0.034). In multivariate logistic regression, there were gradual associations between lower eGFR and CAC when an eGFRCys or eGFRCrCys was used. The adjusted OR for CAC in the group with eGFR <30 mL/min/1.73 m2 compared to the group with eGFR ≥90 mL/min/1.73 m2 was 2.64 (95% CI, 1.09-3.60) when eGFRCrCys was used. Of the four eGFR formulas, only adding eGFRCrCys significantly improved CAC prediction models without eGFR (P = 0.046). CONCLUSIONS: There was a gradual and independent association between low eGFR and CAC in a predialysis CKD cohort in Korea. eGFRCrCys predicted CAC better than other equations in this population.

High fibroblast growth factor 23 is associated with coronary calcification in patients with high adiponectin: analysis from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) study.

Background: The association between fibroblast growth factor 23 (FGF23) and coronary artery calcification (CAC) was inconclusive. Recently it was shown that adiponectin modulates renal handling of calcium and phosphorus. We hypothesized that adiponectin plays a role in the effect of FGF23 on CAC and explored whether the association between FGF23 and CAC is modified by serum adiponectin level in chronic kidney disease (CKD) patients. Methods: This cross-sectional study analyzed 1435 predialysis CKD patients from the Korean Cohort Study for Outcome in Patients with CKD cohort. Participants were divided into two groups according to their serum adiponectin (upper half and lower half). Each group was further divided into three groups according to their FGF23 levels as follows: low (<5.0 RU/mL), middle (5.0-29.9 RU/mL) and high (≥30.0 RU/mL). The coronary artery calcium score (CACS) was assessed using cardiac computed tomography and CAC was defined as a CACS >100. Results: The median CACS did not differ between the low and high adiponectin groups {3.2 [interquartile range (IQR) 0.0-98.1] versus 0.5 [0.0-99.5], P = 0.988}. The CACS ratio comparing high FGF23 to low FGF23 was significantly increased in the high adiponectin group, but not in the low adiponectin group [2.35 (IQR 1.14-4.85) versus 1.10 (0.60-2.03)]. The odds ratio for CAC in the high FGF23 group compared with the low group was 1.97 (IQR 1.10-3.53). The association between FGF23 and CAC was modified significantly by adiponectin level (P for interaction = 0.023). Conclusions: High serum FGF23 was associated with CAC in CKD patients with high adiponectin, but not in those with low adiponectin. Further studies are warranted to verify the role of adiponectin in FGF23-related CAC.

Solitary kidney and risk of chronic kidney disease.

The renal outcome of solitary kidney remains controversial. We examined the longitudinal association of congenital or acquired solitary kidney with the development of chronic kidney disease (CKD). A cohort study was performed involving 271,171 Korean men and women free of CKD at baseline who underwent a health screening program and who were followed annually or biennially for an average of 5.4 years. Solitary kidney was determined based on ultrasonographic findings. CKD was defined as an estimated glomerular filtration rate of < 60 ml/min/1.73 m2 and/or the presence of proteinuria in two or more consecutive visits. During 1,472,519.6 person-years of follow-up, 2989 participants developed CKD (incidence rate: 2.0 per 1000 person-years). After adjustment for potential confounders, the aHR (95% CIs) for incident CKD comparing solitary kidney to the control was 3.26 (1.63-6.54). In analyses of cause-specific solitary kidney, aHR (95% CIs) for CKD comparing unilateral nephrectomy and congenital solitary kidney to the control were 6.18 (2.31-16.49) and 2.22 (0.83-5.92), respectively. The association between solitary kidney and CKD was stronger in men. Having a solitary kidney was independently associated with an increased risk of CKD development. Therefore, preventive strategies for reducing the risk of CKD are required in individuals with a solitary kidney.

Arterial Stiffness as a Risk Factor for Subclinical Coronary Artery Calcification in Predialysis Chronic Kidney Disease: From the KNOW-CKD Study.

BACKGROUND/AIMS: Both arterial stiffness and coronary artery calcification (CAC) are important predictors of cardiovascular disease in the general population and in chronic kidney disease (CKD) patients. Recent studies on arterial stiffness and CAC in subjects with preserved renal function have verified the association between the two. However, the relationship is not well evaluated in CKD patients. METHODS: This cross-sectional study analyzed 1,385 predialysis CKD patients from the KNOW-CKD cohort. Participants were divided into four groups according to brachial-ankle pulse wave velocity (baPWV) quartile. Coronary artery calcium scores (CACS) were assessed using cardiac computed tomography and CAC was defined as a CACS >100. RESULTS: CAC prevalence was higher in the higher baPWV groups (6.4, 9.8, 23.7, and 43.8% for the 1st to 4th quartiles of baPWV, respectively, p < 0.001). In Tobit regression analyses that were fully adjusted for traditional and renal cardiovascular risk factors, the CACS ratio comparing the highest and lowest baPWV quartiles was 3.03 (95% CI, 1.59-6.87). Similarly, the OR for CAC in the highest baPWV quartile compared to the lowest quartile was 1.98 (95% CI, 1.09-3.60) in a fully adjusted multivariate logistic model. Results were consistent across analyses with different cutoffs for CAC or with different clinically relevant subgroups. CONCLUSION: Increased arterial stiffness measured by high baPWV was associated with CAC in a predialysis CKD cohort. Longitudinal studies are needed to determine the effect of arterial stiffness on the development or progression of CAC in CKD.

Body Mass Index, waist circumference, and health-related quality of life in adults with chronic kidney disease.

PURPOSE: Obesity is linked to poor health-related quality of life (HRQOL) in the general population, but its role in chronic kidney disease (CKD) is uncertain. METHODS: We conducted a cross-sectional study that investigated 1880 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) who underwent complete baseline laboratory tests, health questionnaires, and HRQOL. HRQOL was assessed by physical component summary (PCS) and mental component summary (MCS) of the SF-36 questionnaire. We used multivariable linear regression models to examine the relationship between Body Mass Index (BMI) and sex-specific waist circumference (WC) with HRQOL. RESULTS: Adults with higher BMI and greater WC showed lower PCS. After adjusting for age, sex, socioeconomic state, comorbidities, and laboratory findings, we found that WC, but not BMI, was associated with PCS. Greater WC quintiles were associated with lower PCS [WC-4th quintile (ß, - 2.63, 95% CI - 5.19 to - 0.06) and WC-5th quintile (ß, - 3.71, 95% CI - 6.28 to - 1.15)]. The association between WC and PCS was more pronounced in older adults, woman, patients with diabetes, cardiovascular disease, or lower eGFR. The relationship between BMI and WC with MCS was not significant. CONCLUSIONS: In adults with CKD, WC is a better indicator of poor physical HRQOL than BMI. The association between WC and physical HRQOL is modified by age, sex, eGFR, and comorbidities such as diabetes and cardiovascular disease.

Association Between Sonographically Diagnosed Nephrolithiasis and Subclinical Coronary Artery Calcification in Adults.

BACKGROUND: Although recent studies suggest an association between nephrolithiasis and clinical cardiovascular events, this association has been underexplored. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 62,091 asymptomatic adults without known coronary heart disease who underwent a screening health examination that included cardiac tomography. PREDICTOR: Nephrolithiasis. OUTCOME: Coronary artery calcification (CAC). MEASUREMENTS: Nephrolithiasis assessed using ultrasonography of the abdomen. CAC scoring assessed using cardiac computed tomography. RESULTS: The prevalence of CAC scores > 0 was 13.1% overall. Participants with nephrolithiasis had a higher prevalence of coronary calcification than those without (19.1% vs 12.8%). In Tobit models adjusted for age and sex, the CAC score ratio comparing participants with nephrolithiasis with those without nephrolithiasis was 1.56 (95% CI, 1.19-2.05). After further adjustment for screening center, year of screening examination, physical activity, alcohol intake, smoking status, education level, body mass index, family history of cardiovascular disease, total energy intake, glucose concentration, systolic blood pressure, triglyceride concentration, high-density lipoprotein cholesterol concentration, uric acid concentration, and estimated glomerular filtration rate, the CAC score ratio was attenuated, but remained significant (CAC score ratio, 1.31; 95% CI, 1.00-1.71). LIMITATIONS: Computed tomographic diagnosis of nephrolithiasis was unavailable. CONCLUSIONS: Nephrolithiasis was associated with the presence of CAC in adults without known coronary heart disease, supporting the hypothesis that these 2 health conditions share a common pathophysiology.

Trace Urine Albumin and Mortality: Kangbuk Samsung Health Study.

BACKGROUND/AIMS: The importance of a trace albumin on the urine dipstick test is not well known and is frequently disregarded in clinical practice. The aim of this study is to investigate the role of trace albuminuria in predicting all-cause mortality in Korean adults. METHODS: In this retrospective cohort study, we analyzed 347,938 Korean adults who underwent urine dipstick test from 2002 to 2012 in a health examination program. The participants were divided into three groups according to dipstick negative, trace (±), and overt (≥1+) albuminuria. The trace group was further stratified by urine specific gravity (SG) and classified as either high (≥1.020) or low (≤1.015) SG. Mortality data was obtained from STATICS KOREA, a Korean federal statistical organization. RESULTS: During a median follow-up period of 5.9 years, 1,855 deaths occurred. Mortality was compared to negative group and adjusted for potential risk factors. Mortality did not increase in the trace group (HR, 1.19; 95% CI, 0.97-1.47; P=0.097), but increased in the overt (HR, 1.69; 95% CI, 1.38-2.07; P< 0.001) albuminuria group. When the trace group was subdivided according to urine SG, mortality did not increase in the high SG (HR, 1.09; 95% CI, 0.86-1.37; P=0.488) group, but increased in the low SG (HR, 1.84; 95% CI, 1.19-2.83; P=0.006) and overt (HR, 1.70; 95% CI, 1.39-2.08; P< 0.001) groups. CONCLUSION: Trace albumin with low SG in urine dipstick test was associated with higher all-cause mortality in Korean adults. We should not neglect the significance of trace albumin and SG when interpreting urinalysis results.

Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study.

BACKGROUND: The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. OBJECTIVE: To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. DESIGN: Prospective cohort study. SETTING: Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. PARTICIPANTS: 62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. MEASUREMENTS: Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. RESULTS: During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal-weight participants were -4.0 (95% CI, -7.8 to -0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups. LIMITATION: Chronic kidney disease was identified by a single measurement at each visit. CONCLUSION: Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function. PRIMARY FUNDING SOURCE: None.

Nutritional Status in Adults with Predialysis Chronic Kidney Disease: KNOW-CKD Study.

Adverse changes in nutrition are prevalent and are strong indicators of adverse outcomes in patients with chronic kidney disease (CKD). The International Society of Renal Nutrition and Metabolism (ISRNM) proposed a common nomenclature and diagnostic criteria to identify protein-energy wasting (PEW) in CKD patients. We examined the nutritional status in 1,834 adults with predialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) study. As there was a need for further understanding of nutritional status and associated factors in CKD, we evaluated the prevalence and associated factors of PEW in adults with predialysis CKD. The prevalence of PEW was about 9.0% according to ISRNM criteria and tended to increase with advanced stage in predialysis CKD. Those who concurrently had PEW, inflammation, and CVD were a small proportion (0.4%). In multivariate logistic regression model, PEW was independently associated with estimated glomerular filtration rate (eGFR) (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99), total CO2 (OR, 0.93; 95% CI, 0.87-0.99), physical activity (OR, 0.43; 95% CI, 0.26-0.69), comorbid diabetes (OR, 1.68; 95% CI, 1.09-2.59), and high sensitivity C-reactive protein (hs-CRP) (OR, 1.03; 95% CI, 1.01-1.06). Our study suggests that PEW increases with advanced CKD stage. PEW is independently associated with renal function, low total CO2, low physical activity, comorbid diabetes, and increased hs-CRP in adults with predialysis CKD.

Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory. As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m². The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.

Association between Urine Creatinine Excretion and Arterial Stiffness in Chronic Kidney Disease: Data from the KNOW-CKD Study.

BACKGROUND/AIMS: Previous studies have shown that low muscle mass is associated with arterial stiffness, as measured by pulse wave velocity (PWV), in a population without chronic kidney disease (CKD). This link between low muscle mass and arterial stiffness may explain why patients with CKD have poor cardiovascular outcomes. However, the association between muscle mass and arterial stiffness in CKD patients is not well known. METHODS: Between 2011 and 2013, 1,529 CKD patients were enrolled in the prospective Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). We analyzed 888 participants from this cohort who underwent measurements of 24-hr urinary creatinine excretion (UCr) and brachial-ankle PWV (baPWV) at baseline examination. The mean of the right and left baPWV (mPWV) was used as a marker of arterial stiffness. RESULTS: The baPWV values varied according to the UCr quartile (1,630±412, 1,544±387, 1,527±282 and 1,406±246 for the 1st to 4th quartiles of UCr, respectively, P<0.001). For each 100 mg/d increase in UCr, baPWV decreased by 6m/sec in a multivariable linear regression model fully adjusted for traditional and renal cardiovascular risk factors. The odds ratio of the 1st quartile for high baPWV (highest quintile of mPWV) compared with the 4th quartile was 2.62 (1.24-5.54, P=0.011) in a logistic model fully adjusted for traditional and renal cardiovascular risk factors. CONCLUSION: Low muscle mass estimated by low UCr was associated high baPWV in pre-dialysis CKD patients in Korea. Further studies are needed to confirm the causal relationship between UCR and baPWV, and the role of muscle mass in the development of cardiovascular disease in CKD.

High estimated glomerular filtration rate is associated with coronary artery calcification in middle-aged Korean men without chronic kidney disease.

BACKGROUND: High estimated glomerular filtration rate (eGFR) as well as low eGFR is associated with cardiovascular morbidity and mortality. Vascular calcification is a suggested link between low eGFR and worse cardiovascular outcome. However, the association between high eGFR and vascular calcification is not known. The aim of this study is to investigate the relationship between high eGFR and coronary artery calcification (CAC). METHODS: This cross-sectional study analyzed middle-aged Korean men in whom coronary artery calcium scores (CACS) and eGFR were measured as part of a health examination program in Korea. Participants with underlying chronic kidney disease (CKD), cardiovascular disease (CVD) and cancer were excluded. CAC was defined as a CACS >100. RESULTS: Among 6986 subjects [age 48.1 (46.5-50.5) years], 321 (4.6%) participants had CAC. The percentages of participants with CAC were 5.7, 3.8, 4.9 and 6.6 in groups with eGFR (mL/min/1.73 m(2)) of 60 ∼ 74, 75 ∼ 89, 90 ∼ 104 and 105 ∼ max, respectively. According to multivariate analysis, the odds ratio for CAC in the group with eGFR of 105 ∼ max compared with the group with eGFR of 75 ∼ 89 was 2.52 (1.67-3.79, P < 0.001) after adjustment for age, body mass index, diabetes, hypertension, systolic blood pressure, glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, hsCRP, calcium, phosphorus, current smoking, alcohol intake and vigorous exercise frequency. CONCLUSIONS: High eGFR is associated with CAC in middle-aged Korean men without CKD. Further studies are needed to verify a causal relationship and clarify the role of high eGFR in the development of CVD.