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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. [ABSTRACT FROM AUTHOR]

Despite the clear association between low BMD and all-cause mortality in the general population, the association has not been validated in patients with nondialysis CKD. To investigate the association of low BMD with all-cause mortality in this population, a total of 2089 patients with nondialysis CKD at stages 1 to predialysis 5 were categorized into normal BMD (T-score ≥ −1.0), osteopenia (−2.5 < T-score < −1.0), and osteoporosis (T-score ≤ − 2.5) by the BMD at femoral neck. The study outcome was all-cause mortality. Kaplan–Meier curve depicted a significantly increased number of all-cause death events in the subjects with osteopenia or osteoporosis during the follow-up period compared with subjects with normal BMD. Cox regression models demonstrated that osteoporosis, but not osteopenia, was significantly associated with an increased risk of all-cause mortality (adjusted hazard ratio 2.963, 95% confidence interval 1.655 to 5.307). Smoothing curve fitting model visualized a clear inverse correlation between BMD T-score and the risk of all-cause mortality. Even after recategorizing the subjects by BMD T-scores at total hip or lumbar spine, the result was similar to the primary analyses. Subgroup analyses revealed that the association was not significantly modified by clinical contexts, such as age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, low BMD is associated with an increased risk of all-cause mortality in patients with nondialysis CKD. This emphasizes that the routine measurement of BMD by DXA may confer an additional benefit beyond the prediction of fracture risk in this population. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common after gastric surgery for gastric cancer and associated with adverse outcomes. However, the impact of transient or persistent AKI on clinical outcomes after gastric surgery for gastric cancer has not been described. We performed a retrospective study of 4,886 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2012. AKI patients were classified as transient and persistent AKI based on the return of serum creatinine to the level indicating no AKI within 7 days. Our outcomes included occurrence of new-onset chronic kidney disease (CKD) and mortality 1 year after gastric surgery. AKI occurred in 638 (13.1%) after gastric surgery. Transient AKI was documented in 574 (90%). Use of diuretics and contrast agents was a common risk factor for persistent and transient AKI. Length of intensive care unit (ICU) and hospital stay, and ICU admission rate were higher in patients with transient AKI than in those without AKI. Although patients with persistent AKI had a higher new-onset CKD 1 year after gastric surgery after adjusting for multiple covariates, transient AKI was not associated with new-onset CKD. The 1-year mortality rates were significantly higher in patients with transient and persistent AKI. Not only persistent AKI but transient AKI is associated with increased risk of hospital complications and a significantly higher risk of long-term mortality than patients without AKI after gastric surgery. Moreover, persistent AKI, but not transient AKI, is associated with CKD progression at 1 year. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To investigate the association between abdominal aortic calcification score (AACS) assessed by plain radiograph of the lateral abdomen and the risk of cardiovascular (CV) events in patients with pre-dialysis chronic kidney disease (CKD), a total of 2090 pre-dialysis CKD patients from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were categorized by AACS into 0, 1–2, 3–4, 5–6, and ≥7. The primary outcome of the study was the composite CV events, defined as a composite of non-fatal CV events and all-cause death. The risk of composite CV events was significantly higher in the subjects with AACS ≥ 7 (adjusted hazard ratio (HR) 1.888, 95% confidence interval (CI) 1.219 to 2.923), compared to that of the subjects with AACS 0. The risks of fatal and non-fatal CV events (adjusted HR 1.052, 95% CI 1.030 to 1.073) and all-cause death (adjusted HR 1.949, 95% CI 1.073 to 3.539) were also significantly higher in the subjects with AACS ≥ 7. In conclusion, AACS assessed by plain radiograph is independently associated with adverse CV outcomes in patients with pre-dialysis CKD. A simple radiographic examination of the lateral abdomen may help CV risk stratification in this population. [ABSTRACT FROM AUTHOR]

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 m2. 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 m2 (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. [ABSTRACT FROM AUTHOR]

Circulating osteoprotegerin (OPG) is a biomarker for cardiovascular complications that are closely related to chronic kidney disease (CKD). To investigate the association between circulating OPG level with long-term visit-to-visit blood pressure variability (BPV) in patients with pre-dialysis CKD, a total of 1855 subjects with CKD from stage 1 to pre-dialysis stage 5 from a prospective cohort were analyzed. Long-term visit-to-visit BPV was determined by average real variability (ARV), standard deviation (SD), and coefficient of variation (CoV) of systolic and diastolic blood pressure (SBP and DBP). ARV of SBP (Adjusted β coefficient 0.143, 95% confidence interval 0.021 to 0.264) was significantly associated with serum OPG level. Although SD and CoV of SBP were not significantly associated with serum OPG level in multivariate linear regression analyses, restricted cubic spline visualized the linear correlation of serum OPG level with all of ARV, SD, and CoV. The association between serum OPG level and DBP variability was not significant. Subgroup analyses revealed that the association of serum OPG with BPV is more prominent in the subjects with Charlson comorbidity index ≤3 and in the subjects without history of diabetes mellitus. In conclusion, circulating OPG level is potentially associated with long-term visit-to-visit BPV in patients with pre-dialysis CKD. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under the age of 60 with high CAC scores using machine learning techniques. We developed the predictive models with a chronic kidney disease representative cohort, the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). We divided the cohort into a training dataset (70%) and a validation dataset (30%). The test dataset incorporated an external dataset of patients that were not included in the KNOW-CKD cohort. Support vector machine, random forest, XGboost, logistic regression, and multi-perceptron neural network models were used in the predictive models. We evaluated the model's performance using the area under the receiver operating characteristic (AUROC) curve. Shapley additive explanation values were applied to select the important features. The random forest model showed the best predictive performance (AUROC 0.87) and there was a statistically significant difference between the traditional logistic regression model and the test dataset. This study will help identify patients at high risk of cardiovascular complications in young chronic kidney disease and establish individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Apparent treatment-resistant hypertension (ATRH) is closely related to chronic kidney disease (CKD); however, the long-term outcomes and the effects of improvement in ATRH in patients with CKD are not well understood. We evaluated the relationship between the persistence of ATRH and the progression of CKD. This cohort study enrolled 1921 patients with CKD. ATRH was defined as blood pressure above 140/90 mmHg and intake of three different types of antihypertensive agents, including diuretics, or intake of four or more different types of antihypertensive agents, regardless of blood pressure. We defined ATRH subgroups according to the ATRH status at the index year and two years later. The prevalence of ATRH at baseline was 14.0%. The presence of ATRH at both time points was an independent risk factor for end-point renal outcome (HR, 1.41; 95% CI, 1.04–1.92; p = 0.027). On the other hand, the presence of ATRH at any one of the time points was not statistically significant. In conclusion, persistent ATRH is more important for the prognosis of renal disease than the initial ATRH status. Continuous follow-up and appropriate treatment are important to improve the renal outcomes. [ABSTRACT FROM AUTHOR]

Obesity has become a pandemic. It is one of the strongest risk-factors of new-onset chronic kidney disease (CKD). However, the effects of obesity and abdominal obesity on the risk of developing CKD in young adults has not been elucidated. From a nationwide health screening database, we included 3,030,884 young adults aged 20–39 years without CKD during a baseline examination in 2009–2010, who could follow up during 2013–2016. Patients were stratified into five levels based on their baseline body mass index (BMI) and six levels based on their waist circumference (WC; 5-cm increments). The primary outcome was the development of CKD. During the follow up, until 2016, 5853 (0.19%) participants developed CKD. Both BMI and WC showed a U-shaped relationship with CKD risk, identifying the cut-off values as a BMI of 21 and WC of 72 cm in young adults. The obesity group (odd ratio [OR] = 1.320, 95% confidence interval [CI]: 1.247–1.397) and abdominal obesity group (male WC ≥ 90, female WC ≥ 85) (OR = 1.208, 95%CI: 1.332–1.290) showed a higher CKD risk than the non-obesity or non-abdominal obesity groups after adjusting for covariates. In the CKD risk by obesity composite, the obesity displayed by the abdominal obesity group showed the highest CKD risk (OR = 1.502, 95%CI: 1.190–1.895), especially in those under 30 years old. During subgroup analysis, the diabetes mellitus (DM) group with obesity or abdominal obesity paradoxically showed a lower CKD risk compared with the non-obesity or non-abdominal obesity group. Obesity and abdominal obesity are associated with increased risk of developing CKD in young adults but a decreased risk in young adults with diabetes. [ABSTRACT FROM AUTHOR]