KoreaN Cohort Study For Outcome Research Articles

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD): A Korean Chronic Kidney Disease Cohort

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.

Machine Learning-Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant Recipients: An Integer-Based Score to Predict Tertiary Hyperparathyroidism.

Tertiary hyperparathyroidism in kidney allograft recipients is associated with bone loss, allograft dysfunction, and cardiovascular mortality. Accurate pretransplant risk prediction of tertiary hyperparathyroidism may support individualized treatment decisions. We aimed to develop an integer score system that predicts the risk of tertiary hyperparathyroidism using machine learning algorithms. We used two separate cohorts: a derivation cohort with the data of kidney allograft recipients (n=669) who underwent kidney transplantation at Severance Hospital, Seoul, Korea between January 2009 and December 2015 and a multicenter registry dataset (the Korean Cohort Study for Outcome in Patients with Kidney Transplantation) as an external validation cohort (n=542). Tertiary hyperparathyroidism was defined as post-transplant parathyroidectomy. The derivation cohort was split into 75% training set (n=501) and 25% holdout test set (n=168) to develop prediction models and integer-based score. Tertiary hyperparathyroidism requiring parathyroidectomy occurred in 5% and 2% of the derivation and validation cohorts, respectively. Three top predictors (dialysis duration, pretransplant intact parathyroid hormone, and serum calcium level measured at the time of admission for kidney transplantation) were identified to create an integer score system (dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level [DPC] score; 0-15 points) to predict tertiary hyperparathyroidism. The median DPC score was higher in participants with post-transplant parathyroidectomy than in those without (13 versus three in derivation; 13 versus four in external validation; P<0.001 for all). Pretransplant dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level score predicted post-transplant parathyroidectomy with comparable performance with the best-performing machine learning model in the test set (area under the receiver operating characteristic curve: 0.94 versus 0.92; area under the precision-recall curve: 0.52 versus 0.47). Serial measurement of DPC scores (≥13 at least two or more times, 3-month interval) during 12 months prior to kidney transplantation improved risk classification for post-transplant parathyroidectomy compared with single-time measurement (net reclassification improvement, 0.28; 95% confidence interval, 0.02 to 0.54; P=0.03). A simple integer-based score predicted the risk of tertiary hyperparathyroidism in kidney allograft recipients, with improved classification by serial measurement compared with single-time measurement. Korean Cohort Study for Outcome in Patients with Kidney Transplantation (KNOW-KT), NCT02042963 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_06_10_CJN15921221.mp3.

Left Ventricular Diastolic Dysfunction and Progression of Chronic Kidney Disease: Analysis of KNOW-CKD Data.

BackgroundFew studies have examined the association between the early diastolic mitral inflow velocity/early diastolic mitral annulus velocity ratio (E/e’) and chronic kidney disease progression.Methods and ResultsWe reviewed data from 2238 patients with nondialysis chronic kidney disease from the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease); data from 163 patients were excluded because of missing content. A >50% decrease in estimated glomerular filtration rate from baseline, doubling of serum creatinine, or dialysis initiation and/or kidney transplantation were considered renal events. At baseline, median (interquartile range) ejection fraction and E/e’ were 64.0% (60.0%–68.0%) and 9.1 (7.4–11.9), respectively. Proportions of ejection fraction <50% and E/e’ ≥15 were 1.3% and 9.6%, respectively. More than one quarter of patients (27.2%) had an estimated glomerular filtration rate <30 mL/min per 1.73 m2. During the mean 59.1‐month follow‐up period, 724 patients (34.9%) experienced renal events. In multivariable Cox proportional hazard regression analysis, the hazard ratio with 95% CI per 1‐unit increase in E/e’ was 1.027 (1.005–1.050; P=0.016). Penalized spline curve analysis yielded a suggested threshold of E/e’ for renal events of 12; in our data set, the proportion of E/e’ ≥12 was 4.1%.ConclusionsIncreased E/e’ was associated with an increased hazard of renal events, suggesting that diastolic heart dysfunction is a novel risk factor for chronic kidney disease progression.

Association Between Systolic Blood Pressure Variability and Major Adverse Cardiovascular Events in Korean Patients With Chronic Kidney Disease: Findings From KNOW-CKD.

BackgroundWhether visit‐to‐visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear.Methods and ResultsWe investigated the relationship between SDs of visit‐to‐visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit‐to‐visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient‐years of follow‐up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit‐to‐visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80–3.36) and 2.23 (95% CI, 1.12–4.44), respectively, in a multivariable cause‐specific hazard model. In addition, the HR associated with each 5‐mm Hg increase in visit‐to‐visit SBP variability (SD) was 1.21 (95% CI, 1.01–1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03–4.35) and 2.28 (95% CI, 1.12–4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87–3.57) and 2.04 (95% CI, 1.03–4.03), respectively, with the variation independent of the mean.ConclusionsHigher visit‐to‐visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Association Between Left Ventricular Geometry and Renal Outcomes in Patients With Chronic Kidney Disease: Findings From Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease Study.

BackgroundThe impact of left ventricular (LV) geometry on the renal outcomes in patients with chronic kidney disease (CKD) has not been established yet. We aimed to investigate the association of LV geometry with renal outcomes and all-cause mortality in patients with pre-dialysis CKD.MethodsA total of 2,144 subjects from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) were categorized by LV geometry, which was defined by LV mass index and relative wall thickness [normal geometry, concentric remodeling, eccentric hypertrophy (eLVH), and concentric hypertrophy (cLVH)]. Study outcomes were composite renal events [decline of kidney function (the first occurrence of > 50% decline of eGFR or doubling of serum creatinine from the baseline) and onset of ESRD (initiation of dialysis or kidney transplantation) during follow-up periods)] and all-cause mortality.ResultsCox regression analysis revealed that eLVH [adjusted hazard ratio (HR) 1.498, 95% confidence interval (CI) 1.197–1.873] and cLVH (adjusted HR 1.289, 95% CI 1.011–1.643) were associated with increased risk of composite renal events, whereas concentric remodeling (adjusted HR 1.881, 95% CI 1.135–3.118) and cLVH (adjusted HR 2.216, 95% CI 1.341–3.664) were associated with increased risk of all-cause mortality. Sensitivity analyses confirmed that concentric remodeling (adjusted HR 1.993, 95% CI 1.197–3.368) and eLVH (adjusted HR 1.588, 95% CI 1.261–2.001) are independently associated with all-cause mortality and composite renal events, respectively.ConclusionIn conclusion, we report that LV geometry is significantly associated with adverse renal outcomes and all-cause mortality in patients with pre-dialysis CKD. Echocardiographic determination of LV geometry may help the early identification for the patients with high risk of CKD progression.

Association of Left Ventricular Diastolic Dysfunction With Cardiovascular Outcomes in Patients With Pre-dialysis Chronic Kidney Disease: Findings From KNOW-CKD Study.

BackgroundThe impact of left ventricular diastolic dysfunction (LVDD) on cardiovascular (CV) outcomes in patients with pre-dialysis chronic kidney disease (CKD) has been rarely unveiled. We here investigated the association of LVDD with CV outcomes and all-cause mortality in patients with pre-dialysis CKD.MethodsA total of 2,135 patients with pre-dialysis CKD from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) cohort were dichotomized by the absence or presence of LVDD, which was defined as the ratio of the early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e′) > 14.ResultsCox regression analysis revealed that LVDD was significantly associated with increased risk of composite CV events [adjusted hazard ratio (HR) 2.194, 95% confidence interval (CI) 1.486–3.240] and all-cause mortality (adjusted HR 1.830, 95% CI 1.168–2.869). Restricted cubic splines visualized stringent linear correlations of E/e′ with both composite CV events and all-cause mortality. In the sensitivity analysis only including the subjects with left ventricular ejection fraction ≥ 50%, LVDD was still significantly associated with adverse CV outcomes (adjusted HR 1.984, 95% CI 1.325–3.000) and all-cause mortality (adjusted HR 1.727, 95% CI 1.083–2.754), suggesting that the impact of LVDD on the outcomes in patients with CKD is independent of LV systolic function. Subgroup analyses revealed that the associations were not modified by various clinical contexts, such as age, sex, burden of comorbid conditions, body mass index, estimated glomerular filtration rate, and albuminuria.ConclusionLVDD is independently associated with adverse CV outcomes and all-cause mortality in patients with pre-dialysis CKD.

Baseline characteristics of participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD).

We developed the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD) as a subcohort of KNOW-CKD to investigate the different characteristics of pediatric CKD between countries and races. Children aged younger than 18years with stage 1 ~ 5 CKD were recruited at seven major pediatric nephrology centers in Korea. Blood and urine samples, as well as demographic and clinical data, were collected. From 2011 to 2016, 458 children were enrolled, and the baseline profiles of 437 children were analyzed. The median age of the cohort was 10.9years old, and 68.0% were males. The median estimated glomerular filtration rate was 53.1mL/min/1.73 m2. The most common etiology of CKD was congenital anomalies of the kidney and urinary tract (42.6%), followed by glomerulopathies (25.6%). We report a cross-sectional analysis of the overall baseline characteristics such as age, CKD stage, and underlying kidney disease of the KNOW-Ped CKD. The cohort will be longitudinally followed for ten years. "A higher resolution version of the Graphical abstract is available as Supplementary information."

Abdominal Aortic Calcification and Cardiovascular Outcomes in Chronic Kidney Disease: Findings from KNOW-CKD Study.

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.

The Association between Health-Enhancing Physical Activity and Quality of Life in Patients with Chronic Kidney Disease: Propensity Score Matching Analysis.

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.

Association between serum osteoprotegerin level and renal prognosis in nondialysis patients with chronic kidney disease in the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (the KNOW-CKD Study)

BackgroundOsteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients.MethodsWe analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression.ResultsThe median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041–1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results.ConclusionSerum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression.

Predictive Model for High Coronary Artery Calcium Score in Young Patients with Non-Dialysis Chronic Kidney Disease.

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.

Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort.

BackgroundDiabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs).MethodsThe analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined.ResultsAmong all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant.ConclusionSocioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD

Background and aimsThe optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and resultsA total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression.During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. ConclusionsThis study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

Association of Body Weight Variability with Adverse Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease.

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.

Effects of blood urea nitrogen independent of the estimated glomerular filtration rate on the development of anemia in non-dialysis chronic kidney disease: The results of the KNOW-CKD study.

Anemia is a common complication of chronic kidney disease (CKD). Blood urea nitrogen (BUN) in CKD represents nitrogenous uremic toxin accumulation which could be involved in anemia of CKD. We investigated the effects of BUN independent of estimated glomerular filtration rate (eGFR) on anemia in non-dialysis CKD (NDCKD). This prospective study included 2,196 subjects enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort with BUN and hemoglobin level data. Initially, we investigated the association between BUN and hemoglobin level. To examine the impact of baseline BUN on the incident anemia, a longitudinal study was performed on 1,169 patients without anemia at study enrollment. BUN residuals were obtained from the fitted curve between BUN and eGFR. Anemia was defined as a hemoglobin level of <13.0 g/dL for men and <12.0 g/dL for women. BUN residuals were not related to eGFR but to daily protein intake (DPI), while BUN was related to both eGFR and DPI. BUN was inversely associated with hemoglobin level (β -0.03; 95% confidence interval [CI] -0.04, -0.03; P <0.001) in the multivariable linear regression analysis adjusted for multiple confounders including eGFR, and BUN residual used instead of BUN was also inversely associated with hemoglobin level (β -0.03; 95% CI -0.04, -0.02; P <0.001). Among the 1,169 subjects without anemia at baseline, 414 (35.4%) subjects newly developed anemia during the follow-up period of 37.5 ± 22.1 months. In the multivariable Cox regression analysis with adjustment, both high BUN level (Hazard ratio [HR] 1.02; 95% CI 1.01, 1.04; P = 0.002) and BUN residual used instead of BUN (HR 1.02; 95% CI 1.00, 1.04; P = 0.031) increased the risk of anemia development. Moreover, BUN, rather than eGFR, increased the risk of anemia development in patients with CKD stage 3 in the multivariable Cox regression. Higher BUN levels derived from inappropriately high protein intake relative to renal function were associated with low hemoglobin levels and the increased risk of anemia independent of eGFR in NDCKD patients.

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

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. 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. 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. 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.

Association Between Longitudinal Blood Pressure Trajectory and the Progression of Chronic Kidney Disease: Results From the KNOW-CKD.

[Figure: see text].

Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.

BackgroundThe function of high‐density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high‐density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease .Methods and ResultsIn total, 1864 patients from the prospective KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high‐density lipoprotein cholesterol (HDL‐C) level. Presence of inflammation was defined by hs‐CRP (high‐sensitivity C‐reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person‐years of follow‐up, overall incidence of the primary outcome was 15.8 per 1000 person‐years. In multivariable Cox analysis after adjusting for confounders, HDL‐C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL‐C for risk of extended major adverse cardiovascular events (P=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL‐C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50–1.82), 0.95 (0.50–1.82), and 0.42 (0.19–0.95), respectively, compared with HDL‐C of 40 to 49 mg/dL. However, the significant association for HDL‐C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL‐C groups (HRs [95% CIs], 0.73 [0.37–1.43], 1.24 [0.59–2.61], and 1.56 [0.71–3.45], respectively), but without statistical significance.ConclusionsThe association between HDL‐C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study

BackgroundAlthough uric acid (UA) is regarded as a risk factor for cardiovascular disease, whether UA is an independent risk factor contributing to coronary artery calcification in chronic kidney disease (CKD) is not well known. We evaluated whether UA level is associated with coronary artery calcium (CAC) score in a predialysis CKD cohort.MethodsA total of 1,350 subjects who underwent coronary computed tomography as part of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease were analysed. We conducted a logistic regression analysis to evaluate the association between UA and the presence of CAC.ResultsCAC was detected in 705 (52.2 %) patients, and the level of UA was significantly higher in CAC > 0 patients. UA showed a positive relationship with CAC > 0 in age- and sex-adjusted logistic regression analysis (Odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.04–1.19, P = 0.003). However, UA showed no association with CAC > 0 in multivariate analysis. Further analysis showed that UA showed a positive association with CAC > 0 only in estimated glomerual filtration rate (eGFR) > 60 ml/min/1.73 m2 (OR 1.23, 95 % CI 1.02–1.49, P = 0.036) but not in eGFR 30–59 ml/min/1.73 m2 (OR 0.92, 95 % CI 0.78–1.08, P = 0.309) or < 30 ml/min/1.73 m2 (OR 0.92, 95 % CI 0.79–1.08, P = 0.426).ConclusionsUA level was significantly associated with CAC in early CKD, but not in advanced CKD.

Low serum adiponectin level is associated with better physical health-related quality of life in chronic kidney disease

Hyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1–T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend < 0.001). The adjusted OR [95% CI] of T1 and T2 in reference to T3 were 1.56 [1.09–2.23] and 1.19 [0.85–1.68] for high PCS and 1.19 [0.85–1.68] and 0.94 [0.68–1.29] for high MCS. Serum adiponectin level was inversely associated with physical HR-QOL in Korean pre-dialysis CKD patients. This relationship was independent of various cardiovascular risk factors.