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The transtubular potassium gradient which reflects potassium secretion by the kidney through the cortical collecting duct, has not yet been tested as a surrogate marker of kidney function decline. Here, we investigate the relationship between the transtubular potassium gradient and chronic kidney disease (CKD) progression. We studied 1672 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. The transtubular potassium gradient was calculated using a standard equation. The study endpoint was CKD progression, defined as a composite of a ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from baseline values or end-stage kidney disease. During a median follow-up of 4.1 years (7149 person-years), 441 participants reached the endpoint. In cause-specific competing risk analysis, the highest tertile was associated with a significantly lower risk of an adverse kidney outcome compared with the lowest tertile [hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.97]. When the transtubular potassium gradient was treated as a continuous variable, an increase of 1 in the transtubular potassium gradient was associated with a 6% lower risk of CKD progression (95% CI, 0.90–0.99). This association was particularly evident in patients with an eGFR ≥ 45 mL/min/1.73 m2. A time-updated transtubular potassium gradient model showed similar results. The predictive performance of the transtubular potassium gradient was significantly less than that of the eGFR, but similar to that of proteinuria, serum bicarbonate, and urine osmolality. A higher transtubular potassium gradient is associated with a significantly lower risk of CKD progression, suggesting that it may offer insights into the prognosis of CKD.

Background and Aims Osteoprotegerin (OPG), which is an osteoclastic inhibitory factor, have been shown associated with adverse renal outcomes and progression of vascular calcification in chronic kidney disease (CKD) patients. Anemia and CKD-bone mineral disorders (CKD-MBD) are also frequently observed in these patients. Since CKD-MBD and anemia might be closely linked, therefore, we further examined whether OPG level as a marker for bone turnover can predict the future development of anemia in a large-scale prospective cohort. Method Among 2,238 patients with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD), 2,086 patients who measured hemoglobin, hepcidin, iron profiles and OPG level were included in the analysis. Anemia was defined as a hemoglobin level of < 13.0 g/dL and 12.0 g/dL for male and female, respectively. Results The mean age was 53.6 ± 12.2 years and 1,270 (60.9%) patients were males. At baseline, anemia was found in 941 (45.1%) patients. Log transformed OPG levels significantly correlated with FGF23 levels, but inversely with iron profiles and hemoglobin levels at baseline. A multivariate logistic regression model showed that log OPG level was independently associated with the prevalence of anemia (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.41-3.48, P=0.001). Among 1110 patients without baseline anemia, 258 (25.3%) patients developed anemia during a median follow-up duration of 34.6 (interquartile range, 23-48) months. In the fully adjusted multivariable Cox models, risk of developing anemia was significantly higher in the fourth (hazard ratio [HR], 1.99; 95% CI, 1.08-3.67; P =0.028) than in the first OPG quartile. Similar association was observed in a model when OPG was treated as a continuous variable. Conclusion We showed that high serum OPG levels are associated with an increased risk of developing anemia in patients with non-dialysis CKD.

Background and Aims Anemia was frequently observed in chronic renal failure patients. The risk of osteoporosis is higher in patients with chronic anemia. Chronic anemia also showed a close relationship with bone mineral density. However, few studies have been done whether anemia affects bone mineral density with chronic kidney disease(CKD) patient. Therefore, the aim of our study is to evaluate the relationship between anemia and bone mineral density(BMD) in a large sample of non-dialysis CKD cohort. Method We performed an observational study in 2,089 patients who measured hemoglobin and BMD with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Anemia was defined as hemoglobin(Hb) levels of < 13.0 g/dL for males and 12.0 g/dL for females, respectively. BMD was estimated by dual energy x-ray absorptiometry system. The observed variable was decline of BMD during follow up. Results The mean age was 53.6 ± 12.2 years and 1,292(61.1%) patients were males. The BMD score was positively correlated with hemoglobin levels (β, 0.007; 95% CI, 0.003-0.012; P 0.002), but inversely with prevalence of anemia (β, -0.03; 95% CI, -0.042--0.008; P 0.004). In the multivariable logistic regression model, the prevalence of osteoporosis was significantly higher in the anemia group than that in the normal hemoglobin levels (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.11-2.51, P=0.014). Among 881 patients except unavailable following BMD, 396 (19.7%) patients developed the decline of BMD during a median follow-up duration of 48 (interquartile range, 46-49) months. In the fully adjusted multivariable Cox models, risk of developing the decline of BMD was significantly higher in the anemia group (HR, 1.38; 95% CI, 1.02-1.87; P= 0.036) as compared to normal hemoglobin group. Conclusion We found that anemia is independently and significantly correlated with an increased risk of osteoporosis with non-dialysis CKD. Our study suggests that prompt correction of anemia in CKD patients could be beneficial to preserving bone mineral density.

Background and Aims Osteoprotegerin (OPG), which is an osteoclastic inhibitory factor, is associated with type 2 diabetes mellitus, severity of vascular calcification, coronary artery disease, and chronic kidney disease. Obesity is a risk factor for diabetes, and cardiovascular disease, however there are few studies about the relationship between OPG and obesity, especially in patients with CKD. This study aimed to investigate association between OPG level and obesity in a large-scale prospective cohort. Method Among 2,238 patients with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD), 1,970 patients who measured body mass index (BMI), waist circumference (WC) and OPG level were included in the analysis. Obesity were defined as having a BMI >25 kg/m2 and WC > 90 cm in male, > 85 cm in female. Results The mean age was 53.6 ± 12.2 years and 1,196 (60.7%) patients were males. At baseline, obesity by BMI, WC, and composite of BMI and WC were found in 814 (41.3%), 208 (26.9%) and 1,137 (57.7%) patients. A multivariate logistic regression model showed that log transformed OPG level was independently associated with the prevalence of obesity by BMI, WC, composite of BMI and WC (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.16-0.65, P Conclusion We showed that serum OPG levels are associated with obesity in patients with non-dialysis CKD.

Background and Aims Hypoxia has been considered to be a risk factor for osteoporosis. Several studies have reported on the close associations between the anemia and an increased risk of bone loss. However, the relationship between hemoglobin levels and bone mineral density(BMD) has not been established in chronic kidney disease (CKD) patients. Therefore, the aim of this study is to investigate the relationship between BMD and anemia in a non-dialysis CKD cohort. Method Among 2,238 patients with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD), 2,115 patients who measured hemoglobin(Hb) and BMD were included in the analysis. We defined anemia as hemoglobin(Hb) levels of < 13.0 g/dL and 12.0 g/dL for males and females, respectively. The primary endpoint was the onset of a 15% decline in Hemoglobin during follow-up. Results The mean age was 53.6 ± 12.2 years and 1,292(61.1%) patients were males. The BMD score was positively correlated with hemoglobin levels (β, 0.658; 95% CI, 0.215-1.101; P 0.004). In the multivariable logistic regression model, the prevalence of anemia was significantly higher in the osteoporosis group than that in the normal BMD group (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.03-2.46, P=0.038). Among 1010 patients without data of following hemoglobin levels, 396 (19.7%) patients developed 15% decline in hemoglobin level during a median follow-up duration of 36 (interquartile range, 10-60) months. In the fully adjusted multivariable Cox models, risk of developing the 15% decline of hemoglobin was significantly higher in the osteoporosis group (HR, 1.45; 95% CI, 1.03-2.05; P= 0.035) as compared to normal BMD group. Conclusion This study showed that low bone mass density was independently related with anemia and hemoglobin levels in patients with non-dialysis CKD. Our findings suggest that preserve bone mass be important to maintain the levels of hemoglobin with CKD patients.

Severe weather conditions, such as heavy snowfall, rain, heatwave, etc., may affect travel behaviors of people and finally change traffic patterns in transportation networks. Hence, this study has focused on the impacts of a weather condition on travel patterns of public transportations, especially when a heavy snowfall which is one of the most critical weather conditions. First, this study has figured out the most significant weather condition affecting changes of public transport ridership using weather information, card data for public transportation, mobile phone data; and then, developed a decision tree model to determine complex inter-relations between various factors such as socio-economic indicators, transportation-related information. As a result, the trip generation of public transportations in Seoul during a heavy snowfall is mostly related to average access times to subway stations by walk and the number of available parking lots and spaces. Meanwhile, the trip attraction is more related to business and employment densities in that destination.

Parabens and triclosan have been widely used in many personal care products and cosmetics. The endocrine disrupting potential of these compounds is of increasing public health concern. The aim of this study is to understand the current exposure profile of these chemicals in last void before bedtime (night-time) and first-morning void (first-morning) urines among a Korean population and to characterize their exposure sources and pathways. A total of 261 people, including infants (0–2 years), toddlers (3–6 years), children (7–12 years), adolescents (13–18 years), and adults (≥19 years), were recruited, and sampled for night-time urine and first-morning urine of the following day. Methyl (MeP), ethyl (EtP), propyl (PrP) and butyl paraben (BuP), and triclosan were measured in urine. The demographic characteristics, use of personal care products, and food consumption were obtained through a questionnaire. Among the target compounds, EtP and MeP were most frequently detected at the highest concentrations. The median concentration of EtP in night-time urine was 32.4 μg/L (interquartile range: 8.37–82.8 μg/L), which is higher than previously reported worldwide. Unlike other test compounds, compared to those measured from first-morning urine, the EtP concentrations were significantly higher in night-time urine, suggesting the presence of different exposure sources. Among adults, the MeP and PrP concentrations in night-time urine were associated with frequent use of skin care products, colored cosmetics, bath products, toothpaste, vinyl food packaging, or consumption of canned food. The MeP and PrP concentrations were higher in females than in males, especially in night-time urine. The results of this study also show that multiple urine samples are necessary to capture the diurnal variation of non-occupational exposure to environmental chemicals, such as parabens.

Phthalates are anti-androgenic chemicals and may cause long-lasting adverse effects on growing fetuses. Understanding their exposure profile during pregnancy, therefore, is of public health importance. Because both behavioral and physiological changes of pregnant women are expected to be substantial, the amount of phthalate exposure is expected to vary significantly over the course of pregnancy. Temporal trend of phthalate exposure during pregnancy, however, is largely unknown, especially in Asian women. The purpose of this study is to investigate the urinary concentrations of metabolites for major phthalates and alternative plasticizers over the course of pregnancy among Korean (n = 81) and Thai women (n = 102). Twenty-four metabolites from 15 plasticizers, such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), dioctyl phthalate (DnOP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-ethylhexyl) terephthalate (DEHTP), and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH), were measured in urine samples collected in each trimester from pregnant women. While the levels of several phthalate metabolites were significantly different by trimester among Korean women, those of Thai women were relatively consistent. Urinary metabolites of DEP and DnOP were higher in Thai pregnant women compared to Korean pregnant women. The detection frequencies of the DINCH metabolite were 67.4% and 44.9% among Korean and Thai pregnant women, respectively. However, the ratio of DINCH to DEHP metabolites was significantly higher in Thai women. According to risk assessment, 11.9% of Korean and 5.3% of Thai women were considered at risk due to phthalate exposure, and DEHP, DnBP and DiBP were identified as major risk drivers. Considering the vulnerability of growing fetuses, further studies are warranted to identify major sources of exposure to these plasticizers during pregnancy.

In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGB1A is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALIs. HMGB1A has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGB1A, the HMGB1A/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti-inflammatory effect. Complex formation with HMGB1A and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113nm and -25mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A/heparin complex reduced pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, more effectively than HMGB1A or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1A/heparin complex might be useful to treat ALI.

Acute lung injury (ALI) is an inflammatory lung disease caused by sepsis, infection, or ischemia-reperfusion. The receptor for advanced glycation end-products (RAGE) signaling pathway plays an important role in ALI. In this study, a novel RAGE-antagonist peptide (RAP) was produced as an inhibitor of the RAGE signaling pathway based on the RAGE-binding domain of high mobility group box-1 (HMGB1). Recombinant RAP was over-expressed and purified using nickel-affinity chromatography. In lipopolysaccharide- or HMGB1-activated RAW264.7 macrophage cells, RAP reduced the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). RAP decreased the levels of cell surface RAGE and inhibited the nuclear translocation of nuclear factor-κB (NF-κB). These results imply that RAP decreases RAGE-mediated NF-κB activation and subsequent inflammatory reaction. For in vivo evaluation, RAP was delivered to the lungs of ALI-model animals via intratracheal administration. As a result, RAGE was down-regulated in the lung tissues by pulmonary delivery of RAP. Consequently, TNF-α, IL-6, and IL-1β were also reduced in broncoalveolar lavage fluid and the lung tissues of RAP-treated animals. Hematoxylin and eosin staining indicated that inflammation was decreased in RAP-treated animals. Collectively, these results suggest that RAP may be a useful treatment for ALI.

Background: Aldosterone-induced glomerular hyperfiltration can lead to masked preoperative renal dysfunction in primary aldosteronism(PA) patients. We evaluated whether PA patients had a higher prevalence of acute kidney injury (AKI) after unilateral adrenalectomy. In addition, we identified risk factors for AKI in these subjects. Methods: This retrospective study included 107 PA patients, and 186 pheochromocytoma patients as a control group, all of whom underwent adrenalectomy between January 2006 and November 2017 at Yonsei University Severance Hospital. The primary outcome was AKI within 48 hours after adrenalectomy. Univariate and multivariate logistic regression analyses were performed to identify predictors of AKI after adrenalectomy. Results: Overall incidence of AKI was 49/293 (16.7%). In PA patients, the incidence of AKI was 29/107 (27.1%). In contrast, incidence of AKI was 20/ 186 (10.7%) in pheochromocytoma patients. Univariate and multivariate logistic regression analysis both showed a higher risk of postoperative AKI in PA patients compared to pheochromocytoma patients. In addition, old age, diabetes, longer duration of hypertension, lower preoperative estimated glomerular filtration rate, high aldosterone-cortisol ratio (ACR) and lateralization index (LI) were identified as independent risk factors for postoperative AKI in PA patients after unilateral adrenalectomy. Conclusion: Incidence and risk of postoperative AKI were significantly higher in PA patients after surgical treatment. High ACR on the tumor side and high LI were associated with higher risk of AKI in PA patients compared to pheochromocytoma patients.