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

Background/aims: The neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in cardiovascular disease, infection, inflammatory disease, and several malignancies. Therefore, the NLR has a possible predictive value in patients with chronic kidney disease (CKD), but this predictive value has not been validated. Here, we aimed to investigate the possibility of NLR as a predictor of CKD progression., Methods: This retrospective observational study included 141 patients with non-dialysis CKD. The participants were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome was defined as a composite kidney event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or initiation of renal replacement therapy during the follow-up period., Results: The mean follow-up duration was 5.45 ± 2.11 years. The mean NLRs were 1.35 ± 0.05 in T1 (n = 47), 2.16 ± 0.04 in T2 (n = 47), and 4.29 ± 0.73 in T3 (n = 47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence rate of composite kidney events was significantly higher in T3 compared with T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was associated with the risk of composite kidney events (adjusted hazard ratio, 3.33; 95% confidence interval, 1.43-7.76)., Conclusion: A higher NLR reflects the more advanced stage of CKD and suggests a role for NLR as a biomarker for predicting CKD progression.

The relationship between 24-h urinary phosphorus excretion (24 h UPE) and cardiovascular disease in patients with pre-dialysis chronic kidney disease (CKD) has rarely been studied, despite the fact that the relationship between serum phosphorus level and the risk of a cardiovascular event is well established. A total of 1701 patients with pre-dialysis CKD were finally included for the analyses and were divided into tertiles by 24 h UPE (first tertile (T1, 349.557 (mean) ± 88.413 (standard deviation)), second tertile (T2, 557.530 ± 50.738), and third tertile (T3, 851.695 ± 171.593). The study outcome was a six-point major adverse cardiac event (MACE). The median follow-up duration was 7.992 years. Kaplan-Meier curve analysis visualized that the cumulative incidences of a six-point MACE ( p = 0.029) significantly differed from 24 h UPE levels, as the incidence rate of the study outcomes was highest in T1 and lowest in T3. Cox proportional hazard models unveiled that, compared to T1, the risk of a six-point MACE was significantly decreased in T3 (adjusted hazard ratio (HR) 0.376, 95% confidence interval (CI) 0.207 to 0.683). The restricted cubic spline curve analysis visualized an inverted S-shaped association between 24 h UPE level and the risk of a six-point MACE, indicating a significantly increased risk of a six-point MACE in patients with a low 24 h UPE level. In conclusion, low 24 h UPE is associated with adverse cardiovascular outcomes in patients with CKD. Our finding emphasizes that low 24 h UPE should not be a reliable marker for dietary restriction of phosphorus that essentially leads to better outcomes in patients with CKD.

As the relation between serum non-high-density lipoprotein cholesterol (nHDL) level and renal outcomes has never been investigated in patients with non-dialysis chronic kidney disease (CKD) yet, we here aimed to unveil the association of nHDL with CKD progression. A total of 2152 patients with non-dialysis CKD at stages 1 to 5 from the KNOW-CKD study were categorized into the tertile (i.e., 1st (T1), 2nd (T2), and 3rd (T3) tertiles) by nHDL, and were prospectively analyzed. The primary outcome was the composite renal event, defined as a composite of decline of kidney function or onset of end-stage renal disease. Kaplan-Meier survival curves analysis demonstrated that the cumulative incidence of the composite renal event was significantly increased in T1 and T3, compared to T2 ( p = 0.028, by Log-rank test). Cox regression analysis revealed that both T1 (adjusted hazard ratio 1.309, 95% confidence interval 1.074-1.595) and T3 (adjusted hazard ratio 1.272, 95% confidence interval 1.040-1.556) are associated with significantly increased risk of a composite renal event, compared to T2. The restricted cubic spline plot demonstrated a non-linear, U-shaped association between nHDL and the risk of a composite renal event. In conclusion, both low and high serum nHDL levels are associated with increased risk of CKD progression.

As non-high-density lipoprotein cholesterol (non-HDL-C) levels account for all atherogenic lipoproteins, serum non-HDL-C level has been suggested to be a marker for cardiovascular (CV) risk stratification. Therefore, to unveil the association of serum non-HDL-C levels with CV outcomes in patients with non-dialysis chronic kidney disease (ND-CKD), the patients at stages 1 to 5 ( n = 2152) from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into quintiles by serum non-HDL-C level. The primary outcome was a composite of all-cause death or non-fatal CV events. The median duration of follow-up was 6.940 years. The analysis using the Cox proportional hazard model unveiled that the composite CV event was significantly increased in the 5th quintile (adjusted hazard ratio 2.162, 95% confidence interval 1.174 to 3.981), compared to that of the 3rd quintile. A fully adjusted cubic spline model depicted a non-linear, J-shaped association between non-HDL-C and the risk of a composite CV event. The association remained robust in a series of sensitivity analyses, including the analysis of a cause-specific hazard model. Subgroup analyses reveled that the association is not significantly altered by clinical conditions, including age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, high serum non-HDL-C level increased the risk of adverse CV outcomes among the patients with ND-CKD. Further studies are warranted to define the optimal target range of non-HDL-C levels in this population.

The prognostic value of urinary angiotensinogen (UAGT) in patients with chronic kidney disease (CKD) has not been completely evaluated, although the association of UAGT with renal outcomes has been suggested in specific subsets of CKD. In the present study, to investigate the association of UAGT with renal outcomes in patients with non-dialysis CKD irrespective of the primary cause, a total of 1688 subjects from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into the quintile by UAGT to urine creatinine ratio (UAGT/Cr) level. The primary outcomes of interest were composite renal event, which included decline in kidney function and onset of end-stage renal disease during follow-up periods. The median follow-up duration was 6.257 years. Cox regression model analysis unveiled that the risk of composite renal event was significantly higher in the fifth quintile (adjusted hazard ratio 1.528, 95% confidence interval 1.156 to 2.021) compared to that of the first quartile. The association between high UAGT/Cr level and adverse renal outcome remained consistent in sensitivity analyses, including the analysis of the cause-specific hazard model. Subgroup analyses revealed that the association of UAGT level with renal outcomes is modified by certain clinical contexts, such as BMI and albuminuria. In conclusion, high UAGT level is associated with adverse renal outcomes in patients with non-dialysis CKD. Further studies are warranted to elaborate and expand the predictive role of UAGT as a biomarker for renal outcomes in CKD.

Background: Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on development of end-stage renal disease (ESRD) in patients with diabetes., Methods: A total of 2 563 870 patients with diabetes aged >20 years were selected from the Korean National Health Screening Program from 2009 to 2012 and followed up until the end of 2019. Participants were categorized into age and BP groups, and the hazard ratios for ESRD were calculated., Results: During a median follow-up of 7.15 years, the incidence rates of ESRD increased with increasing SBP and DBP. The hazard ratio for ESRD was the highest in patients younger than 40 years of age with DBP≥100 mm Hg. The effect of SBP and DBP on ESRD development was attenuated with age (interaction P was <0.0001 for age and SBP, and 0.0022 for age and DBP). The subgroup analysis for sex, antihypertension medication, and history of chronic kidney disease showed higher hazard ratios for ESRD among males, younger than 40 years, not taking antihypertension medications and chronic kidney disease compared to those among females, older than 40 years, antihypertension medication, and nonchronic kidney disease groups., Conclusions: Higher SBP and DBP increase the risk of developing ESRD in patients with diabetes, and in particular, younger individuals face greater risk. Therefore, intensive BP management is warranted in younger patients to prevent ESRD.

Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and β-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of β-elemene was demonstrated by in vivo and in vitro experiments. It was shown that β-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-β stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that β-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-β stimulated NRK49F cell, which may be a novel molecular mechanism by which β-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of β-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.

We investigate the association between health-enhancing physical activity and the quality of life in patients with non-dialysis chronic kidney disease. We performed data analysis on 1618 of 2238 patients from 2011 to 2016, obtained from the KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD). Health-related quality of life was measured using the Korean version 1.3 of Kidney Disease Quality of Life short-form questionnaire. Health-enhancing physical activity was defined as 150 min of moderate-intensity or 75 min of vigorous-intensity aerobic physical activity throughout the week. Propensity score matching analysis and linear regression was performed to estimate the effect of health-enhancing physical activity on health-related quality of life. The estimate of average treatment effects was 2.60 in the kidney component summary score, 4.45 in the physical component summary score, and 4.24 in the mental component summary score. In all component summary scores and most of their subscales, health-enhancing physical activity showed a significant association with health-related quality of life. Subgroup and sensitivity analyses also showed robust results. This study suggests that health-enhancing physical activity elevated quality of life in patients with non-dialysis chronic kidney disease. The results can contribute to encourage physical activity in patients with chronic kidney disease.

Dietary potassium intake is a dilemma in patients with chronic kidney disease (CKD). We investigated the association of urine potassium excretion, a surrogate for dietary potassium intake, with blood pressure variability (BPV) and cardiovascular (CV) outcomes in patients with pre-dialysis CKD. A total of 1860 participants from a cohort of pre-dialysis CKD (KNOW-CKD) patients were divided into the quartiles by spot urine potassium-to-creatinine ratio. The first quartile (26.423 ± 5.731 mmol/gCr) was defined as low urine potassium excretion. Multivariate linear regression analyses revealed an independent association of low urine potassium excretion with high BPV (adjusted β coefficient 1.163, 95% confidence interval 0.424 to 1.901). Cox regression analyses demonstrated that, compared to high urine potassium excretion, low urine potassium excretion is associated with increased risk of CV events (adjusted hazard ratio 2.502, 95% confidence interval 1.162 to 5.387) but not with all-cause mortality. In conclusion, low urine potassium excretion is associated with high BPV and increased risk of CV events in patients with pre-dialysis CKD. The restriction of dietary potassium intake should be individualized in patients with pre-dialysis CKD.

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.

Background/aims: This study aimed to investigate whether urinary angiotensinogen (UAGT) excretion was associated with elevated blood pressure in patients with chronic kidney disease (CKD) and to evaluate the relationship among blood pressure, intra-renal renin-angiotensin system (RAS) activity, and dietary sodium in patients with CKD., Methods: Participants from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were included. Of the total cohort of 2,238 individuals with CKD, we included 1,955 participants who underwent complete 24-hour urinary sodium (24-hour UNa) analysis. They were categorized into three groups according to three tertiles of their 24-hour UNa, reflecting daily salt intake. To measure intra-renal RAS activity, the UAGT excretion was assayed with an enzyme-linked immunosorbent assay., Results: Elevated 24-hour UNa levels, logarithm of UAGT-to-creatinine ratio (UAGT/Cr), increased waist-to-hip ratio, and decreased estimated glomerular filtration rate were the risk factors for increased systolic blood pressure. Systolic blood pressure showed a positive correlation with 24-hour UNa levels and logarithm of UAGT/Cr., Conclusion: UAGT and urinary sodium excretion are independent determinants of systolic blood pressure in patients with CKD. These findings suggest that increased systolic blood pressure in CKD patients is associated with both increased dietary sodium levels and intra-renal RAS activity. The risk of elevated systolic blood pressure in the 3rd tertile of both the UAGT/Cr and 24-hour UNa groups was about 2.3 times higher than that in the reference group.

Background Hypertension among young adults is common. However, the effect of isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), or systolic and diastolic hypertension (SDH) among young adults on chronic kidney disease (CKD) development is unknown. Methods and Results From a nationwide health screening database, we included 3 030 884 participants aged 20 to 39 years who were not taking antihypertensives at baseline examination in 2009 to 2010. Participants were categorized as having normal blood pressure (BP), elevated BP, stage 1 IDH, stage 1 ISH, stage 1 SDH, stage 2 IDH, stage 2 ISH, and stage 2 SDH. The primary outcome was incident CKD. A total of 5853 (0.19%) CKD events occurred. With normal BP as the reference, multivariable-adjusted hazard ratios (HRs) (95% CIs) for CKD were 1.14 (95% CI, 1.04-1.26), elevated BP; 1.19 (95% CI, 1.10-1.28), stage 1 IDH; 1.24 (95% CI, 1.08-1.42), stage 1 ISH; 1.39 (95% CI, 1.28-1.51), stage 1 SDH; 1.88 (95% CI, 1.63-2.16), stage 2 IDH; 1.84 (95% CI, 1.54-2.19), stage 2 ISH; 2.70 (95% CI, 2.44-2.98), stage 2 SDH. The HRs for CKD were attenuated in the patients who were antihypertensive and began medication within 1 year of medical checkup than in those without antihypertensives. Conclusions Among Korean young adults, those with elevated BP, stage 1 IDH, stage 1 ISH, stage 1 SDH, stage 2 IDH, stage 2 ISH, and stage 2 SDH were associated with a higher CKD risk than those with normal BP. The CKD risk in ISH and IDH groups was similar but lower than that in the SDH group. Antihypertensives attenuated the risk of CKD in young adults with hypertension.

Autophagy is important for cells to break down and recycle cellular proteins, remove damaged organelles, and especially, for recovery from acute kidney injury (AKI). Despite research on the role and cellular mechanism of autophagy in AKI, the role of autophagy in the progression to chronic kidney disease (CKD) remains poorly understood. Here, using farnesoid X receptor (FXR) knockout (KO) mice, we determined whether FXR prevents the progression of AKI to CKD after renal ischemic-reperfusion (such as I/R) injury through the regulation of renal autophagy and apoptosis. FXR regulated genes that participate in renal autophagy under feeding and fasting conditions, such as hepatic autophagy, and the activation of FXR by agonists, such as GW4064 and INT-747, attenuated the increased autophagy and apoptosis of hypoxia-induced human renal proximal tubule epithelial (HK2) cells. The expression levels of autophagy-related and apoptosis-related proteins in FXR KO mice were increased compared with those in wild-type (WT) mice. We also showed that the increase in reactive oxidative species (ROS) in hypoxia-treated HK2 cells was attenuated by treatment with FXR agonist or by FXR overexpression, and that the level of ROS was elevated in FXR-deficient cells and mice. At 28 days after I/R injury, the autophagy levels were still elevated in FXR KO mice, and the expression levels of fibrosis-related proteins and ROS deposits were higher than those in WT mice. In conclusion, the regulation of renal autophagy and apoptosis by FXR may be a therapeutic target for the early stages of kidney damage, and the progression of AKI to CKD.

The impact of obesity on health-related quality of life (HRQoL) in chronic kidney disease (CKD) population has not been elucidated, despite the impairment of HRQoL in the obese among general population. We hypothesized that the impact of obesity on HRQoL might be confounded by impaired renal function in CKD population, and that CKD would attenuate the impact of obesity on HRQoL. To compare the impact of obesity on HRQoL according to kidney function, 17,001 subjects from Korea National Health and Nutrition Examination Survey (2008-2011) were categorized by estimated glomerular filtration rate (eGFR), as follows: group 1, eGFR ≥ 90 mL/min/1.73 m 2 ; group 2, eGFR of 60-89 mL/min/1.73 m 2 ; group 3, eGFR < 60 mL/min/1.73 m 2 . The association between obesity parameters (body mass index, waist circumference and, truncal fat mass) and HRQoL parameters (EQ-5D index and EQ-VAS) were cross-sectionally analyzed. Despite robust correlations between obesity parameters and low EQ-5D index or EQ-VAS in general population, no significant association was observed in group 3 population. Impact of obesity on HRQoL in CKD population was only limitedly observed in the mobility domain of EQ-5D, as mobility limitation was associated with increased body mass index or waist circumference regardless of kidney function. Therefore, the impact of obesity on HRQoL seems significantly attenuated in CKD population, suggesting that the risk of obesity should not be over-estimated in patients with CKD, especially with respect to HRQoL.

Chronic underhydration and malnutrition can be associated with irreversible renal damage. This study investigated the association of meal frequency and breakfast skipping with chronic kidney disease (CKD) in South Korea. Participants (4370 participants from the Korean National Health and Nutrition Examination Survey VI 2013-2014) were divided into two groups based on meal frequency: ≥ 15 or < 15 meals/week. They were further divided into four groups based on the frequency of breakfast, lunch, and dinner consumed in the previous year. The data were analyzed with complex samples logistic regression. We found that 9.6% of the participants ( n = 412) had CKD, which was associated with gender, body mass index, serum fasting glucose, daily calorie intake, hypertension, diabetes, and cerebrovascular accident. Participants consuming <15 meals/week had a higher risk of CKD than those who consumed ≥15 meals/week (adjusted odds ratio [OR] 1.531, 95% confidence interval [CI] 1.209-1.938). Participants who rarely had breakfast showed a higher risk of CKD than those who had breakfast 5-7 times/week (adjusted OR 1.572, 95% CI 1.108-2.231). Our findings suggest that <15 meals/week or skipping breakfast is associated with a higher risk of CKD in the general South Korean population, especially for men or persons aged 42-64 years.

The prevalence rates of hypertension and chronic kidney disease (CKD) are increasing with the aging of the population. Hypertension and CKD are closely related, and hypertension with accompanying CKD is difficult to control. This difficulty controlling blood pressure (BP) can be explained by changes in diurnal variation in BP, such as non-dipping and reverse dipping patterns, increased pulse pressure, and BP variability in CKD patients resulting in a high frequency of nocturnal hypertension or masked hypertension. CKD patients with uncontrolled or nocturnal hypertension are at increased risk for cardiovascular disease, progression of CKD, and all-cause death. Recent studies have shown that intensive reduction of systolic BP below 120 mmHg is seems to favor in CKD patients regardless of the presence or absence of diabetes. As BP control is difficult in patients with CKD, appropriate measurement of BP is important. Automated BP monitoring could reduce the so-called "white coat effect" (spike in BP) that may be triggered by measurement in a clinical setting. Moreover, out-of-office BP monitoring at home or ambulatory BP monitoring for 24 hours may provide critical information regarding diurnal BP variability and nocturnal BP in patients with CKD.

TGF-β/Smad signaling is a major pathway in progressive fibrotic processes, and further studies on the molecular mechanisms of TGF-β/Smad signaling are still needed for their therapeutic targeting. Recently, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was shown to improve renal fibrosis, making it an attractive target for chronic kidney diseases (CKDs). Here, we show the mechanism by which PGC-1α regulates the TGF-β/Smad signaling pathway using HK-2 cell lines stably overexpressing empty vector (mock cells) or human PGC1α (PGC1α cells). Stable PGC-1α overexpression negatively regulated the expression of TGF-β-induced epithelial-mesenchymal transition (EMT) markers (fibronectin, E-cadherin, vimentin, and α-SMA) and EMT-related transcription factors (Snail and Slug) compared to mock cells, inhibiting fibrotic progression. Interestingly, among molecules upstream of Smad2/3 activation, the gene expression of only TGFβRI, but not TGFβRII, was downregulated in PGC-1α cells. In addition, the downregulation of TGFβRI by PGC-1α was associated with the upregulation of let-7b/c , miRNA for which the 3' untranslated region (UTR) of TGFβRI contains a binding site. In conclusion, PGC-1α suppresses TGF-β/Smad signaling activation via targeting TGFβRI downregulation by let-7b/c upregulation.

The prevalence of hyperuricemia and chronic kidney disease (CKD) has been steadily increasing. The role of hyperuricemia and efficacy of uric acid-lowering agents against CKD progression remain controversial. This study aimed to evaluate the effect of hyperuricemia and uric acid-lowering agents on the progression of CKD. A total 2042 patients with CKD were analyzed in the KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD), a prospective cohort study. Patients were classified into quartiles on the basis of their serum uric acid level and the prevalence of advanced CKD was higher in patients with a high uric acid level. A composite renal outcome was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate during the follow-up period. A Cox proportional hazard ratio model was applied to analyze the relationship between composite renal outcome and uric acid levels. The risk of progression to renal failure increased by 28% (hazard ratio [HR], 1.277; 95% confidence interval [CI], 1.212-1.345) for each 1 mg/dl increase in the baseline uric acid level. In multivariate models, an association was found between the highest quartile of uric acid and increased risk of composite renal outcome (HR, 3.590; 95% CI, 2.546-5.063). A propensity score matching analysis was performed to survey the effect of uric acid lowering agent. Both allopurinol and febuxostat did not affect the renal outcome. In conclusion, hyperuricemia appears to be an independent risk factor for composite renal outcome, but allopurinol and febuxostat did not show reno-protective effect.

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 m 2 . 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.

Vitamin D deficiency is a growing health problem in both the general population and in patients with chronic kidney disease (CKD). However, the relationship between serum 25-hydroxyvitamin D levels and health-related quality of life in CKD is not well established. This study examined the association between vitamin D deficiency and quality of life in pre-dialysis CKD patients. Serum 25-hydroxyvitamin D levels and the Korean version of the Kidney Disease Quality of Life short form were obtained for 1844 pre-dialysis CKD patients in the prospective KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). The baseline estimated glomerular filtration rate was 50.26 ± 0.71 mL/min/1.73 m2. We identified 1294 (70.2%) patients with vitamin D deficiency, defined as a 25-hydroxyvitamin D level < 20 ng/ml. The scores of the kidney disease component summary, physical component summary, and mental component summary in the vitamin D deficiency group were significantly lower compared to the scores of those without vitamin D deficiency. The serum 25-hydroxyvitamin D level was independently associated with the kidney disease component summary and mental component summary scores (β = 0.147, p = 0.003 and β = 0.151, p = 0.047). In conclusion, there was a significant association between serum 25-hydroxyvitamin D levels and kidney disease component summary and mental component summary scores in pre-dialysis CKD patients.

This study examined the characteristics of biochemical parameters, bone diseases, and vascular calcification in Korean patients with chronic kidney disease (CKD) not yet on dialysis. Serum levels of fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 (25D), and 1,25-dihydroxyvitamin D3 (1,25D); lumbar spine, total hip, and femur neck bone mineral densities; and brachial-to-ankle pulse wave velocity (baPWV) representing vascular calcification were measured at baseline for 2,238 CKD patients in the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Increases in serum FGF23 and iPTH preceded changes in serum calcium and phosphate, similar to Western populations. However, the 25D and 1,25D levels decreased earlier than serum FGF23 or iPTH increased, with a decreased estimated glomerular filtration rate (eGFR) in Korean CKD patients. Vitamin D deficiency occurred in 76.7% of patients with CKD stage 1. Bone mineral densities were lowest in CKD stage 5 (lumbar spine, -0.64 ± 1.67; total hip, -0.49 ± 1.21; femur neck, -1.02 ± 1.25). Osteoporosis was more prevalent in patients with higher CKD stages. The mean baPWV, abdominal aortic calcification (AAC), and coronary calcium score also increased, with declined eGFR. In conclusion, a decline in serum vitamin D levels was observed in early CKD stages before significant increases of FGF23 and iPTH in the Korean CKD population compared with that in Western populations. Increased bone disease and vascular calcification occurred in early-stage CKD., Competing Interests: The authors have no potential conflicts of interest to disclose.

We report the first case of spondylitis with bacteremia caused by Campylobacter fetus subsp. testudinum identified by 16S ribosomal ribonucleic acid (rRNA) gene sequencing. An 81-year-old man presented with fever and general weakness. His medical history included end-stage renal disease, hypertension, and type 2 diabetes. Despite empirical antibiotic treatment, his fever and back pain persisted. Magnetic resonance imaging with gadolinium enhancement showed a low-signal-intensity lesion in T1-weighted imaging and a high-signal-intensity lesion in T2-weighted imaging at the L3 vertebral body. C. fetus grew on 1 pair of blood cultures. C. fetus subsp. testudinum was identified via 16S rRNA sequencing of the cultivated organisms. The patient recovered uneventfully after 6 weeks of optimal antibiotic treatment, selected using susceptibility tests. C. fetus spondylitis is a very rare disease. In this unique case involving end-stage renal disease, the underlying pathogen was identified by 16S rRNA sequencing.

Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged ≥50 years and with a T-score ≤ -2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: -0.489, 95% confidence interval [CI]: -0.883 to -0.095, P = 0.015), and total hip (B: -0.349, 95% CI: -0.672 to -0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so much for men., Competing Interests: The authors have declared that no competing interests exist.

Background/aims: This study aimed to investigate the prevalence of chronic kidney disease (CKD) and associated risk factors in a high-risk population in Korea., Methods: A total of 6,045 participants aged ≥ 65 years (mean age, 73.0 ± 5.5) with diabetes or hypertension were enrolled. Participants were screened for CKD, which was defined as the presence of albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g) or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2)., Results: The prevalence of CKD was 39.6% (women, 40.3%; men, 38.4%). Albuminuria was detected in 22.6% of participants, whereas eGFR < 60 mL/min/1.73 m(2) was found in 24.6% of participants. The prevalence of CKD by stage was 4.4% for stage 1, 10.4% for stage 2, 23.4% for stage 3, 0.9% for stage 4, and 0.3% for stage 5. Older age, concomitant diabetes and hypertension, higher body mass index, higher systolic and diastolic blood pressure, and higher hemoglobin A1c levels were independently associated with the presence of CKD in multivariate-adjusted analyses that included with age, sex, body mass index, hypertension, diabetes, and smoking., Conclusions: The prevalence of CKD was very high in the present high-risk Korean population. Our results suggest that a screening method for early detection of CKD in high-risk populations is needed in Korea., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Adiponectin, a peptide hormone secreted from adipocytes, exerts anti-diabetic, anti-atherogenic, and anti-inflammatory properties. We aimed to determine the relationship between serum adiponectin levels and albuminuria, and evaluate determinant factors for serum adiponectin in patients with chronic kidney disease (CKD)., Methods: In total, 1442 CKD patients were included and divided into three groups according to their albumin-to-creatinine ratios: patients with normoalbuminuria (N = 228), microalbuminuria (N = 444), and macroalbuminuria (N = 761). Serum adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit., Results: Serum adiponectin was significantly higher in patients with macroalbuminuria than in those without macroalbuminuria (9.7 ± 6.0, 12.4 ± 9.0, and 14.9 ± 11.0 μg/mL in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). Univariate linear regression analysis showed that the serum adiponectin concentrations were correlated with age, the albumin-to-creatinine ratio, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, whereas they were negatively correlated with body mass index, the estimated glomerular filtration rate, and serum albumin and triglyceride levels. The stepwise regression multiple analysis showed that sex; the estimated glomerular filtration rate; body mass index; total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; and logarithm of the albumin-to-creatinine ratio were independently associated with the logarithm of serum adiponectin levels (r = 0.55, p < 0.001)., Conclusion: Serum adiponectin concentrations are higher in patients with increasing albuminuria, and these levels are associated with renal insufficiency and lipid profiles.

Background: This study was aimed to examine the prevalence of metabolic syndrome (MS) and chronic kidney disease (CKD), and the association between MS and its components with CKD in Korea., Methods: We excluded diabetes to appreciate the real impact of MS and performed a cross-sectional study using the general health screening data of 10,253,085 (48.86 ± 13.83 years, men 56.18%) participants (age, ≥ 20 years) from the Korean National Health Screening 2011. CKD was defined as dipstick proteinuria ≥ 1 or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)., Results: The prevalence of CKD was 6.15% (men, 5.37%; women, 7.15%). Further, 22.25% study population had MS (abdominal obesity, 27.98%; hypertriglyceridemia, 30.09%; low high-density cholesterol levels, 19.74%; high blood pressure, 43.45%; and high fasting glucose levels, 30.44%). Multivariate-adjusted analysis indicated that proteinuria risk increased in participants with MS (odds ratio [OR] 1.884, 95% confidence interval [CI] 1.867-1.902, P<0.001). The presence of MS was associated with eGFR<60 mL/min/1.73 m(2) (OR 1.364, 95% CI 1.355-1.373, P<0.001). MS individual components were also associated with an increased CKD risk. The strength of association between MS and the development of CKD increase as the number of components increased from 1 to 5. In sub-analysis by men and women, MS and its each components were a significant determinant for CKD., Conclusions: MS and its individual components can predict the risk of prevalent CKD for men and women.

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) )., (©2014 Wiley Periodicals, Inc.)

Background: Hospital-acquired anemia (HAA) is common in patients with acute myocardial infarction (AMI) and is an independent indicator of long-term mortality in these patients. However, limited information exists regarding the development and prognostic impact of HAA associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in AMI patients., Methods and Results: We retrospectively analyzed 2,289 patients with AMI, and excluded those with anemia at admission. The study population included 1,368 patients, of whom 800 (58.5%) developed HAA. Age, Hgb level at admission, Length of hospital stay, documented in-hospital bleeding and use of glycoprotein IIb/IIIa inhibitor, presence of CKD and occurrence of AKI were significantly associated with the development of HAA. HAA was significantly associated with higher 3-year mortality (4.8% and 11.4% for non-HAA and HAA patients, respectively; P < 0.001). After adjustment for multivariable confounders, the risk for long-term mortality was increased in HAA patients with AKI and/or CKD but not in HAA patients without AKI and/or CKD, compared to non-HAA patients (HAA patients without AKI and CKD, hazard ratio [HR]: 1.34, 95% confidence interval [CI]: 0.70-2.56; HAA patients with either AKI or CKD, HR: 2.80, 95% CI: 1.37-5.73; HAA patients with AKI and CKD, HR: 3.25, 95% CI: 1.28-8.24; compared with the non-HAA group)., Conclusion: AKI and CKD were strongly associated with the development of HAA in AMI patients. HAA, when accompanied by AKI or CKD, is an independent risk predictor for long-term mortality in AMI patients.

Background and Objectives: CKD is a well known poor prognostic factor in myocardial infarction (MI). This study evaluated the prognostic significance of CKD, particularly in association with increasing age, in MI patients., Design, Setting, Participants, & Measurements: This study was based on a retrospective cohort, the Korean Acute Myocardial Infarction Registry. Patients with a discharge diagnosis of MI were analyzed to investigate the association of CKD with mortality risk according to age. A total of 11,268 patients (mean age 63.0±12.6 years) were included and followed for 1 year., Results: In the full cohort, 26% of patients had CKD (n=2929). The prevalence of CKD was higher with advancing age. Eight hundred sixty-one patients (7.6%) died and the interaction for 1-year mortality between age strata and estimated GFR (eGFR) strata was significant (P<0.001). Within each age category, the absolute 1-year mortality was higher in patients with a low eGFR. However, the adjusted relative mortality risk for a low eGFR was lower with increasing age (adjusted hazard ratio [95% confidence interval] for 1-year mortality at eGFR <30 ml/min per 1.73 m(2): 4.84 [1.93-12.15], 4.53 [2.42-8.47], 3.51 [2.42-5.09], and 3.30 [2.41-4.52] for patients aged <55, 55-64, 65-74, and ≥75 years compared with those with eGFR ≥60 ml/min per 1.73 m(2), respectively)., Conclusions: For all age categories, the overall mortality was significantly higher as eGFR declined. The association of a lower eGFR with mortality was weaker with increasing age, indicating that the prognostic significance of CKD in MI patients is age dependent.

Background/aims: Blood pressure (BP) variability is known as a poor prognostic factor for cardiovascular outcomes. This study assessed the prognostic significance of BP variability in association with increasing age in hemodialysis patients., Methods: We retrospectively analyzed 2,174 patients on hemodialysis from March 2005 to December 2012. The impact of intradialytic and interdialytic BP variability on all-cause mortality according to age groups was analyzed., Results: Kaplan-Meier survival curves for 5-year cumulative mortality showed higher mortality in patients with higher intradialytic systolic and diastolic BP variability as well as interdialytic systolic and diastolic BP variability (log-rank p=0.006, <0.001, 0.018 and < 0.001) in patients aged <55 years, but not in older age groups. Cox proportional analysis revealed that 5-year mortality was associated with intradialytic diastolic BP variability in patients aged <55 years (HR, 2.03 CI, 1.24-3.32)., Conclusion: The overall mortality was associated with BP variability in patients aged <55 years, but not in older ages. This result suggests that younger hemodialysis patients with BP variability require further medical attention and intervention to reduce BP variability.

Background: The presence of chronic kidney disease is an independent prognostic factor in patients with myocardial infarction (MI). We compared the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation and the Modification of Diet in Renal Disease (MDRD) study equation with regard to prognostic value in patients with MI., Methods: This study analyzed a retrospective cohort of 11 050 consecutive patients who had MI and were enrolled in the Korea Acute Myocardial Infarction Registry from November 2005 to August 2008. We applied the CKD-EPI equation and the MDRD study equation to determine the estimated glomerular filtration rate (eGFR) in a cohort of patients with MI., Results: The mean eGFR(CKD-EPI) was slightly higher than that of eGFR(MDRD) (73.16 versus 72.23 mL/min/1.73 m(2); P < 0.001). The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73 m(2) was 26.9%, whereas that of eGFR(MDRD) was 28.5%. The area under the receiver operating characteristic curve was significantly larger for predicting the 1-year major adverse cardiovascular event (MACE) and 1-year all-cause mortality with CKD-EPI equation (0.648 versus 0.641, 0.768 versus 0.753, respectively; P < 0.001). The net reclassification index for improvement in risk of 1-year MACE and 1-year all-cause mortality were 4.09% (P< 0.001) and 9.25% (P< 0.001), respectively., Conclusions: The application of the eGFR(CKD-EPI) demonstrated better predictive values for clinical outcomes than eGFR(MDRD) in a cohort of patients with MI.

Background: Despite strong evidence linking decreased glomerular filtration rate (GFR) to worse outcomes, the impact of GFR on mortality and morbidity in patients with acute myocardial infarction (AMI) is not well defined., Study Design: Retrospective cohort study., Setting & Participants: 12,636 patients with AMI in the Korea AMI Registry database from November 2005 to July 2008. 93% of patients in this registry had coronary angiography, and 91% of patients with coronary angiography had percutaneous coronary intervention (PCI)., Predictor: GFR was estimated (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and patients were grouped into 5 eGFR categories: >90, 60-89, 30-59, 15-29, and <15 mL/min/1.73 m(2)., Outcomes: Primary end points were death and in-hospital complications. Secondary end points were major adverse cardiac events (MACEs) during a 1-month (short-term) and 1-year (long-term) follow-up after AMI., Results: Mean eGFR was 72.8 ± 24.6 mL/min/1.73 m(2), mean age was 64 ± 13 years, and 70.4% were men. A graded association was observed between eGFR and clinical outcomes. In adjusted analyses, compared with eGFR >90 mL/min/1.73 m(2), patients with eGFR of 30-59, 15-29, and <15 mL/min/1.73 m(2) experienced increased risks of short- (respective HRs of 2.30 [95% CI, 1.70-3.11], 3.10 [95% CI, 2.14-4.14], and 3.64 [95% CI, 2.44-5.43]; P < 0.001) and long-term MACEs (HRs of 1.58 [95% CI, 1.32-1.90], 2.12 [95% CI, 1.63-2.75], and 2.50 [95% CI, 1.89-3.29]; P < 0.001). Older age, Killip class higher than I, PCI, and high-sensitivity C-reactive protein level also were associated with higher short- and long-term MACEs. Use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and statins was associated with decreased risk of MACEs., Limitations: Single assessment of serum creatinine., Conclusion: eGFR was associated independently with mortality and complications after AMI. PCI, β-blocker, ACE inhibitor or ARB, and statin use were associated with decreased risks of short- and long-term MACEs., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Patients with chronic kidney disease have had conflicting results between drug-eluting stents (DES) and bare-metal stents (BMS). The aim of the present study was to determine whether DES is preferable for the treatment of acute myocardial infarction (AMI) with renal insufficiency, and to elucidate the impact of diabetes mellitus (DM) on outcomes of each stent., Methods and Results: As a part of the Korea Acute Myocardial Infarction Registry (KAMIR), 2,175 AMI patients with renal insufficiency (glomerular filtration rate <60ml/min) comprising 208 patients with BMS and 1,967 DES implantation were selected. Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization. In the overall population, the MACE rate at 1 year was significantly higher in the BMS group than that of DES (44% vs. 26%, P<0.05), which was mainly due to death rather than repeat intervention (44% vs. 26%, P<0.05). In the diabetic group with DES implantation, the MACE rate was higher compared with the DES group without DM, mainly due to repeat intervention (5% vs. 8%, P<0.05)., Conclusions: In AMI patients with renal insufficiency, DES implantation exhibits a favorable 1-year clinical outcome than BMS implantation, and subgroup analysis for diabetic subjects showed worse outcomes in the DM group with implanted DES.