Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.

BACKGROUND: In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus the clinical predictive performance of well-known risk factors warrants further testing in this population. METHODS: The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1-G5 without kidney replacement therapy between 2011 and 2016. The main predictor was the coronary artery calcium score (CACS). The primary outcome was a composite of nonfatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACEs; the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), all CVEs and all-cause mortality. RESULTS: During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate 1.6/100 person-years). In the multivariable Cox model, a 1-standard deviation log increase in the CACS was associated with a 1.67-fold [95% confidence interval (CI), 1.37-2.04] higher risk of the primary outcome. Compared with a CACS of 0, the hazard ratio associated with a CACS >400 was 4.89 (95% CI 2.68-8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, inclusion of the CACS led to modest improvements in prediction indices of the primary outcome compared with well-known conventional risk factors. CONCLUSIONS: In Korean patients with CKD, the CACS was independently associated with adverse cardiovascular outcomes and all-cause death. The CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors.

Comparison of Antibacterial Activities of Korean Pine (Pinus densiflora) Needle Steam Distillation Extract on Escherichia coli and Staphylococcus aureus Focusing on Membrane Fluidity and Genes Involved in Membrane Lipids and Stress.

The antibacterial activity and mechanism of Pinus densiflora extracts against Escherichia coli and Staphylococcus aureus were investigated. The growth inhibition tests of paper diffusion and optical density exhibited that the extracts have potent antibacterial potentials against foodborne pathogens. The measurement of membrane fluidity by fluorescence polarization has indicated that one of the antibacterial mechanisms involves the disruption of membrane integrity resulting in an increase in the membrane fluidity in both of E. coli and S. aureus. The alteration of fatty acid composition was accompanied by the disturbance of membranes thus shifting the proportion of saturated verses unsaturated fatty acids or trans fatty acids from 1.27:1 to 1.35:1 in E. coli and 1.47:1 to 2.31:1 in S. aureus, most likely to compensate for the increased membrane fluidity by means of a higher proportion of saturated fatty acids which is known to render rigidity in membranes. Realtime q-PCR (polymerase chain reaction) analysis of fatty acid synthetic genes and bacterial stress genes revealed that there was minimal influence of P. densiflora extracts on fatty acid genes except for fab I and the stress rpos in E. coli, and relatively greater impact on fatty acid genes and the stress sigB in S. aureus.

Association of blood pressure with cardiovascular outcome and mortality: results from the KNOW-CKD study.

BACKGROUND: Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. METHODS: Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: <110, 110-119, 120-129, 130-139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs. RESULTS: During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7-26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110-119 mmHg, hazard ratios (95% CI) for <110, 120-129, 130-139 and ≥140 mmHg were 2.47 (1.48-4.11), 1.29 (0.80-2.08), 2.15 (1.26-3.69) and 2.19 (1.19-4.01), respectively. MSMs with the most recent SBP also showed similar findings. CONCLUSIONS: In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg.

Soluble ST2 and Galectin-3 as Predictors of Chronic Kidney Disease Progression and Outcomes.

BACKGROUND: Soluble suppression of tumorigenicity-2 (sST2) and galectin-3, novel biomarkers of heart failure and cardiovascular stress, predict cardiovascular events (CVEs) and mortality. However, their relationship with kidney function and adverse outcomes in CKD are uncertain. The purpose of this study was to determine the association between sST2 and galectin-3 with CKD progression and adverse clinical outcomes. METHODS: We measured baseline sST2 and galectin-3 levels in the CKD patient cohort at our institution between October 2013 and December 2014. The primary outcome was CKD progression (kidney failure with replacement therapy or ≥50% reduction in estimated glomerular filtration rate from the baseline). The secondary outcome was the composite of CVEs and death. We used a Cox proportional hazards model to evaluate the associations between sST2 and galectin-3 levels, with kidney and clinical outcomes. RESULTS: In total, 352 patients were enrolled in this study. At baseline, log sST2 and galectin-3 were directly associated with the serum creatinine (Cr) and urine protein-to-Cr ratio. Cox regression analysis showed that the baseline log sST2 level independently predicted CKD progression and composite outcome after adjustment for age, sex, smoking, diabetes mellitus, hypertension, cardiovascular disease, renin-angiotensin system blocker, calcium channel blocker, ß-blocker, diuretics, antiplatelet agents, anemia, and hypoalbuminemia. The baseline log galectin-3 level was independently associated with CKD progression, but not with the composite outcome after adjustment for confounding variables. CONCLUSIONS: Elevated levels of sST2 and galectin-3 are significantly associated with CKD progression, but only sST2 is associated with adverse clinical outcomes.

Polypharmacy and the Progression of Chronic Kidney Disease: Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

INTRODUCTION: The renal hazard of polypharmacy has never been evaluated in predialysis chronic kidney disease (CKD) patients. OBJECTIVE: We aimed to analyze the renal hazard of polypharmacy in predialysis CKD patients with stage 1-5. METHOD: The data of 2,238 patients from a large-scale multicenter prospective Korean study (2011-2016), excluding 325 patients with various missing data, were reviewed. Polypharmacy was defined as taking 6 or more medications at the time of enrollment; renal events were defined as a ≥50% decrease in kidney function from baseline values, doubling of the serum creatinine levels, or initiation of renal replacement treatment. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox proportional-hazard regression analysis. RESULTS: Of the 1,913 patients, the mean estimated glomerular filtration rate was 53.6 mL/min/1.73 m2. The mean medication count was 4.1, and the prevalence of polypharmacy was 27.1%. During the average period of 3.6 years, 520 patients developed renal events (27.2%). Although increased medication counts were associated with increased renal hazard with HR (95% CI) of 1.056 (1.007-1.107, p = 0.025), even after adjusting for various confounders, adding comorbidity score and kidney function nullified the statistical significance. In mediation analysis, 55.6% (p = 0.016) of renal hazard in increased medication counts was mediated by the kidney function, and there was no direct effect of medication counts on renal event development. In subgroup analysis, the renal hazard of the medication counts was evident only in stage 1-3 of CKD patients (p for interaction = 0.014). CONCLUSIONS: We cannot identify the direct renal hazard of multiple medications, and most of the potential renal hazard was derived from intimate relationship with disease burden and kidney function.

Rapid Weight Change Over Time Is a Risk Factor for Adverse Outcomes in Patients With Predialysis Chronic Kidney Disease: A Prospective Cohort Study.

OBJECTIVE: Both obesity and being underweight are risk factors for adverse outcomes in chronic kidney disease (CKD) patients. However, the effects of longitudinal weight changes on patients with predialysis CKD have not yet been studied. In this study, we analyzed the effects of weight change over time on the adverse outcomes in predialysis CKD population. METHODS: Longitudinal data from a multicenter prospective cohort study (KNOW-CKD) were analyzed. In a total of 2,022 patients, the percent weight change per year were calculated using regression analysis and the study subjects were classified into five categories: group 1, ≤ -5%/year; group 2, -5< to ≤ -2.5%/year; group 3, -2.5< to <2.5%/year; group 4, 2.5≤ < 5%/year; and group 5, ≥5%/year. The incidences of end-stage renal disease (ESRD) and the composite outcome of cardiovascular disease (CVD) and death were calculated in each group and compared to group 3 as reference. RESULTS: During a median 4.4 years of follow-up, 414 ESRD, and 188 composite of CVD and mortality events occurred. Both weight gain and loss were independent risk factors for adverse outcomes. There was a U-shaped correlation between the degree of longitudinal weight change and ESRD (hazard ratio 3.61, 2.15, 1.86 and 3.66, for group 1, 2, 4 and 5, respectively) and composite of CVD and death (hazard ratio 2.92, 2.15, 1.73 and 2.54, respectively), when compared to the reference group 3. The U-shape correlation was most prominent in the subgroup of estimated glomerular filtration rate <45 mL/min/1.73 m2. CONCLUSION: Both rapid weight gain and weight loss are associated with high risk of adverse outcomes, particularly in the advanced CKD.

Hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease.

BACKGROUND: Few studies have examined the association between hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease (CKD) patients. METHODS: We reviewed the data of 2238 patients from a large-scale multicenter prospective Korean study (2011-16) and excluded 214 patients with missing data on markers and related medications of iron and bone mineral metabolism, hemoglobin, blood pressure and causes of CKD. Multivariate linear regression analysis was used to identify the association between iron and bone mineral metabolism. RESULTS: The proportion of CKD Stages 1-5 were 16.2, 18.7, 37.1, 21.6 and 6.4%, respectively. Per each 10% increase in transferrin saturation (TSAT), there was a 0.013 mmol/L decrease in phosphorus [95% confidence interval (CI) -0.021 to -0.004; P = 0.003] and a 0.022 nmol/L increase in logarithmic 25-hydroxyvitamin D (Ln-25OHD) levels (95% CI 0.005-0.040; P = 0.019). A 1 pmol/L increase in Ln-ferritin was associated with a 0.080 ng/L decrease in Ln-intact parathyroid hormone (Ln-iPTH; 95% CI -0.122 to -0.039; P < 0.001). Meanwhile, beta (95% CI) per 1 unit increase in phosphorus, Ln-25OHD and Ln-iPTH for the square root of the serum hepcidin were 0.594 (0.257-0.932; P = 0.001), -0.270 (-0.431 to -0.108; P = 0.001) and 0.115 (0.004-0.226; P = 0.042), respectively. In subgroup analysis, the relationship between phosphorus, 25OHD and hepcidin was strongest in the positive-inflammation group. CONCLUSIONS: Markers of bone mineral metabolism and iron status, including hepcidin, were closely correlated to each other. Potential mechanisms of the relationship warrant further studies.

The effect of interactions between proteinuria, activity of fibroblast growth factor 23 and serum phosphate on renal progression in patients with chronic kidney disease: a result from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease study.

BACKGROUND: Recent experimental study reported that proteinuria increases serum phosphate by decreasing biologic activity of fibroblast growth factor 23 (FGF-23). We examined this relationship in a large chronic kidney disease (CKD) cohort and evaluated the combined effect of proteinuria, FGF-23 activity and serum phosphate on CKD progression. METHODS: The activity of FGF-23, measured by the fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria in 1909 patients with CKD. Primary outcome was CKD progression defined as ≥50% decline of estimated glomerular filtration rate, doubling of serum creatinine and start of dialysis. RESULTS: There was a negative relationship between 24-h urine protein (24-h UP) and FEP/FGF-23 ratio (γ -0.07; P = 0.005). In addition, after matching variables associated with serum phosphate, patients with more proteinuria had higher serum phosphate (P < 0.001) and FGF-23 (P = 0.012), and lower FEP/FGF-23 ratio (P = 0.007) compared with those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was an independent risk factor for CKD progression (hazard ratio 0.87 per 1 log increase; 95% confidence interval 0.79-0.95; P = 0.002), and there was significant interaction between 24-h UP and FEP/FGF-23 ratio (P = 0.039). Furthermore, 24-h UP and serum phosphate also had a significant interaction on CKD progression (P < 0.001). CONCLUSIONS: Proteinuria is associated with decreased biologic activity of FGF-23 and increased serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.

Discrepant glomerular filtration rate trends from creatinine and cystatin C in patients with chronic kidney disease: results from the KNOW-CKD cohort.

BACKGROUND: Serum creatinine (Cr) and cystatin C (CysC) can both be used to estimate glomerular filtration rate (eGFRCr and eGFRCysC). However, certain conditions may cause discrepancies between eGFR trends from Cr and CysC, and these remain undetermined in patients with chronic kidney disease (CKD). METHODS: A total of 1069 patients from the Korean CKD cohort (KNOW-CKD), which enrolls pre-dialytic CKD patients, whose Cr and CysC had been followed for more than 4 years were included in the sample. We performed trajectory analysis using latent class mixed modeling and identified members of the discrepancy group when patient trends between eGFRCr and eGFRCysC differed. Multivariate logistic analyses with Firth's penalized likelihood regression models were performed to identify conditions related to the discrepancy. RESULTS: Trajectory patterns of eGFRCr were classified into three groups: two groups with stable eGFRCr (stable with high eGFRCr and stable with low eGFRCr) and one group with decreasing eGFRCr. Trajectory analysis of eGFRCysC also showed similar patterns, comprising two groups with stable eGFRCysC and one group with decreasing eGFRCysC. Patients in the discrepancy group (decreasing eGFRCr but stable & low eGFRCysC; n = 55) were younger and had greater proteinuria values than the agreement group (stable & low eGFRCr and eGFRCysC; n = 706), differences that remained consistent irrespective of the measurement period (4 or 5 years). CONCLUSIONS: In the present study, we identify conditions related to discrepant trends of eGFRCr and eGFRCysC. Clinicians should remain aware of such potential discrepancies when tracing both Cr and CysC.

Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease.

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC 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.

Correction to: The association between socioeconomic disparities and left ventricular hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

Following publication of the original article [1], an error in one of the author names was reported. In this Correction the incorrect and correct author names are listed.

The association between socioeconomic disparities and left ventricular hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

BACKGROUND: Left ventricular hypertrophy (LVH) is one of the risk factors for cardiovascular (CV) disease and mortality. However, the relationship between socioeconomic status (SES) and LVH in chronic kidney disease remains unclear. METHODS: Data were collected from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at http://www.clinicaltrials.gov ). Subjects with CKD and aged ≥50 were included. SES was characterized based on monthly income and educational attainment, each of which was divided into three strata. LVH was defined as LV mass/height2.7 ≥ 47 g/m2.7 in female and ≥ 50 g/m2.7 in male. Age, sex, diabetes, CKD stage, body mass index, blood pressure and physical activity were included as covariates. RESULTS: A total of 1361 patients were included. Mean age was 60.9 ± 6.9 years, and 63.2% were men. Higher education level was associated with higher monthly income (P for trend < 0.001). The lowest education level was independently associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95% CI 1.069-2.063, P = 0.018; completed high school, adjusted OR 1.150, 95% confidence interval [CI] 0.834-1.584, P = 0.394; highest education level as the reference). Monthly income level was marginally associated with LVH after adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866-1.748, P = 0.247; < $1500, adjusted OR 1.471, 95% CI 1.002-2.158, P = 0.049; > $4500; reference). CONCLUSIONS: In the CKD population, lower SES, defined by educational attainment and low income level exhibited a significant association with LVH, respectively. Longitudinal follow-up will reveal whether lower SES is associated with poor CKD outcomes.

The Correlation of Serum Osteoprotegerin with Non-Traditional Cardiovascular Risk Factors and Arterial Stiffness in Patients with Pre-Dialysis Chronic Kidney Disease: Results from the KNOW-CKD Study.

BACKGROUND: Osteoprotegerin (OPG) plays protective roles against the development of vascular calcification (VC) which greatly contributes to the increased cardiovascular events in patients with chronic kidney disease (CKD). The present study aimed to find the non-traditional, kidney-related cardiovascular risk factors correlated to serum OPG and the effect of serum OPG on the arterial stiffness measured by brachial ankle pulse wave velocity (baPWV) in patients with the pre-dialysis CKD. METHODS: We cross-sectionally analyzed the data from the patients in whom baPWV and the serum OPG were measured at the time of enrollment in a prospective pre-dialysis CKD cohort study in Korea. RESULTS: Along with traditional cardiovascular risk factors such as age, diabetes mellitus, pulse pressure, and baPWV, non-traditional, kidney-related factors such as albuminuria, plasma level of hemoglobin, total CO2 content, alkaline phosphatase, and corrected calcium were independent variables for serum OPG in multivariate linear regression. Reciprocally, the serum OPG was positively associated with baPWV in multivariate linear regression. The baPWV in the 3rd and 4th quartile groups of serum OPG were higher than that in the 1st quartile group after adjustments by age, sex and other significant factors for baPWV in linear mixed model. CONCLUSION: Non-traditional, kidney-related cardiovascular risk factors in addition to traditional cardiovascular risk factors were related to serum level of OPG in CKD. Serum OPG level was significantly related to baPWV. Our study suggests that kidney-related factors involved in CKD-specific pathways for VC play a role in the increased secretion of OPG into circulation in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01630486.

The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation.

BACKGROUND: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia. METHODS: In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL. RESULTS: Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (-) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score ≥2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL). CONCLUSIONS: Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks.

Serum Hepcidin and Iron Indices Affect Anemia Status Differently According to the Kidney Function of Non-Dialysis Chronic Kidney Disease Patients: Korean Cohort Study For Outcome in Patients with Chronic Kidney Disease (KNOW-CKD).

BACKGROUND/AIMS: No studies have examined the association among serum hepcidin, iron indices, or anemia status based on the kidney function of non-dialysis chronic kidney disease (CKD) patients. METHODS: We reviewed data of 2238 patients from a large-scale multicenter prospective Korean study (2011-2016) and excluded 198 patients with missing data regarding serum hepcidin, hemoglobin, transferrin saturation (TSAT), ferritin, and usage of erythropoiesis-stimulating agents (ESA) or supplemental iron and 363 patients using ESA or supplemental iron. Finally, 1677 patients were included. RESULTS: The mean patient age was 53.5 years, and 65.4% were men. TSAT and serum hepcidin were significantly associated with anemia status, whereas serum ferritin was not, regardless of anemia severity. For patients with an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2, a 10% increase of TSAT was associated with hemoglobin <13 g/dL (odds ratio [OR], 0.628; 95% confidence interval [CI], 0.515-0.765; P<0.001) and hemoglobin <11.5 g/dL (OR, 0.672; 95% CI, 0.476-0.950; P=0.024), whereas a 10-ng/mL increase of serum hepcidin was associated with hemoglobin <11.5 g/dL (OR, 1.379; 95% CI, 1.173-1.620; P<0.001) and hemoglobin <10.0 g/dL (OR, 1.360; 95% CI, 1.115-1.659; P=0.002) for patients with eGFR <45 mL/min/1.73 m2 according to multivariate logistic analysis. CONCLUSIONS: TSAT was associated with less severe anemia in early CKD patients. Serum hepcidin was associated with more severe anemia in advanced CKD patients.

Association of serum adiponectin concentration with aortic arterial stiffness in chronic kidney disease: from the KNOW-CKD study.

BACKGROUND: High serum adiponectin levels predict all-cause and cardiovascular mortality in chronic kidney disease (CKD). However, the relationship between serum adiponectin concentration and arterial stiffness in CKD is not well established. The aim of this study was to assess this relationship by measuring pulse wave velocity (PWV) in CKD patients. METHODS: Serum adiponectin concentration was measured in 716 CKD patients in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease. The study group consisted of 415 men and 301 women; mean age was 53.1 years, and baseline estimated glomerular filtration rate (eGFR) was 51 ± 29 ml/min per 1.73 m2. Heart to femoral PWV (hfPWV) and mean brachial to ankle PWV (baPWV) served as indicators of aortic artery stiffness and arterial stiffness, respectively. RESULTS: Increasing quartiles of serum adiponectin levels were associated with women, lower eGFRs and body mass indices, and higher urinary albumin-creatinine ratios. Serum adiponectin concentration also correlated with hfPWV and mean baPWV, even after adjusting for age and sex. It independently associated with hfPWV (B 0.028; 95 % confidence interval, 0.004-0.051; P = 0.020) but not mean baPWV in a multivariable linear regression analysis. In a multivariable logistic regression analysis, it correlated significantly with the highest quartile of hfPWVs but not mean baPWVs. CONCLUSION: The independent and significant correlation of serum adiponectin concentration with hfPWV in CKD patients implicates adiponectin in CKD-associated aortic stiffness.

Total kidney and liver volume is a major risk factor for malnutrition in ambulatory patients with autosomal dominant polycystic kidney disease.

BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD), malnutrition may develop as renal function declines and the abdominal organs become enlarged. We investigated the relationship of intra-abdominal mass with nutritional status. METHODS: This cross-sectional study was performed at a tertiary hospital outpatient clinic. Anthropometric and laboratory data including serum creatinine, albumin, and cholesterol were collected, and kidney and liver volumes were measured. Total kidney and liver volume was defined as the sum of the kidney and liver volumes and adjusted by height (htTKLV). Nutritional status was evaluated by using modified subjective global assessment (SGA). RESULTS: In a total of 288 patients (47.9% female), the mean age was 48.3 ± 12.2 years and the mean estimated glomerular filtration rate (eGFR) was 65.3 ± 25.3 mL/min/1.73 m2. Of these patients, 21 (7.3%) were mildly to moderately malnourished (SGA score of 4 and 5) and 63 (21.7%) were at risk of malnutrition (SGA score of 6). Overall, patients with or at risk of malnutrition were older, had a lower body mass index, lower hemoglobin levels, and poorer renal function compared to the well-nourished group. However, statistically significant differences in these parameters were not observed in female patients, except for eGFR. In contrast, a higher htTKLV correlated with a lower SGA score, even in subjects with an eGFR ≥45 mL/min/1.73 m2. Subjects with an htTKLV ≥2340 mL/m showed an 8.7-fold higher risk of malnutrition, after adjusting for age, hemoglobin, and eGFR. CONCLUSIONS: Nutritional risk was detected in 30% of ambulatory ADPKD patients with relatively good renal function. Intra-abdominal organomegaly was related to nutritional status independently from renal function deterioration.

Associations between Soluble Receptor for Advanced Glycation End Products (sRAGE) and S100A12 (EN-RAGE) with Mortality in Long-term Hemodialysis Patients.

Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612-2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566-1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.

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.