KoreaN Cohort Study For Outcome Research Articles

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.

Sex disparities and adverse cardiovascular and kidney outcomes in patients with chronic kidney disease: results from the KNOW-CKD.

Longitudinal studies of the association between sex and adverse clinical outcomes in patients with chronic kidney disease (CKD) are scarce. We assessed whether major outcomes may differ by sex among CKD patients. We analyzed a total of 1780 participants with non-dialysis CKD G1-5 from the KoreaN cohort study for Outcome in patients with Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of non-fatal cardiovascular events or all-cause mortality. Secondary outcomes included fatal and non-fatal cardiovascular events, all-cause mortality, and a composite kidney outcome of ≥ 50% decline in estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease. There were 1088 (61%) men and 692 (39%) women in the study cohort. The proportion of smokers was significantly higher in men (24% vs. 3%). During 8430 person-years of follow-up, 201 primary outcome events occurred: 144 (13%) in men and 57 (8%) in women, with corresponding incidence rates of 2.9 and 1.7 per 100 person-years, respectively. In multivariable Cox models, men were associated with a 1.58-fold (95% CI 1.06-2.35) higher risk of composite outcome. Propensity score matching analysis revealed similar findings (HR 1.81; 95% CI 1.14-2.91). Risk of all-cause mortality was significantly higher in men of the matched cohort. However, there was no difference in the risk of CKD progression. In the subgroup with coronary artery calcium (CAC) measurements, men had a higher likelihood of CAC progression. In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women.

POS-332 QUALITY OF LIFE IN PATIENTS WITH DIABETIC NEPHROPATHY: FINDINGS FROM THE KNOW-CKD (KOREAN COHORT STUDY FOR OUTCOME IN PATIENTS WITH CHRONIC KIDNEY DISEASE) COHORT

Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences at baseline and after 5 years between DN anDiabetic nephropathy (DN) is a major cause of end-stage renal disease, and can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences at baseline and after 5 years between DN and non-DN patients with other chronic kidney disease (CKD).d non-DN patients with other chronic kidney disease (CKD). The analysis included subjects (n=1766) from the KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form (KDQOL-SF). The factors that influenced the QoL of participants with DN (n=390) were first analyzed, and differences in QoL between DN and non-DN participants was examined. To maintain homogeneity, most factors that influenced the QoL of participants with DN were controlled by propensity score-matched pair sampling using the greedy matching technique. In total, 239 DN and 239 non-DN subjects were finally selected, and differences in the mean KDQOL-SF scores between the 2 groups were then analyzed. In the multivariate linear regression model, higher QoL scores were found for taller DN subjects and lower QoL scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts and alkaline phosphatase levels, and used clopidogrel or insulin. Patient satisfaction (59.9 vs. 64.5, P=0.022) and general health (35.3 vs. 39.1, P=0.041) were significantly lower in the DN group than in the non-DN group. Scores generally 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 patients with DN than among non-DN patients, but the differences were not statistically significant. In conclusion, among the DN subjects, socioeconomic factors were found to be strong risk factors for impaired QoL, as well as high platelet counts, high alkaline phosphatase levels, and clopidogrel and insulin use. The DN subjects showed lower QoL than the non-DN subjects in the domains of patient satisfaction and general health. In conclusion, we confirmed that DN itself affected QoL more strongly than other types of CKD.

Incidence of and risk factors for short stature in children with chronic kidney disease: results from the KNOW-Ped CKD.

Preserving optimal growth has long been a significant concern for children with chronic kidney disease (CKD). We aimed to examine the incidence of and risk factors for short stature in Asian pediatric patients with CKD. We analyzed growth status by height, weight, and body mass index (BMI) standard deviation scores (SDSs) for 432 participants in the KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease. The median height, weight, and BMI SDSs were - 0.94 (interquartile range (IQR) - 1.95 to 0.05), - 0.58 (IQR - 1.46 to 0.48), and - 0.26 (IQR - 1.13 to 0.61), respectively. A high prevalence of short stature (101 of 432 patients, 23.4%) and underweight (61 of 432 patients, 14.1%) was observed. In multivariable logistic regression analysis, CKD stages 4 and 5 (adjusted odds ratio (aOR) 2.700, p = 0.001), onset before age 2 (aOR 2.928, p < 0.0001), underweight (aOR 2.353, p = 0.013), premature birth (aOR 3.484, p < 0.0001), LBW (aOR 3.496, p = 0.001), and low household income (aOR 1.935, p = 0.030) were independent risk factors associated with short stature in children with CKD. Children with CKD in Korea were shorter and had lower body weight and BMI than the general population. Short stature in children with CKD was most independently associated with low birth weight, followed by premature birth, onset before age 2, CKD stages 4 and 5, underweight, and low household income. Among these, underweight is the only modifiable factor. Therefore, we suggest children with CKD should be carefully monitored for weight, nutritional status, and body composition to achieve optimal growth.

Association between the transtubular potassium gradient and progression of chronic kidney disease: results from KNOW-CKD.

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. Thetranstubular 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 4.1years (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 thetranstubular 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 ≥ 45mL/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 highertranstubular potassium gradient is associated with a significantly lower risk of CKD progression, suggesting that it may offer insights into the prognosis of CKD.

Association of Blood Pressure With the Progression of CKD: Findings From KNOW-CKD Study

Optimal blood pressure (BP) control is a major therapeutic strategy in the management of chronic kidney disease (CKD). We studied the association between BP and adverse kidney outcomes within a diverse cohort of Koreans with CKD. Prospective observational cohort study. 2,044 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Baseline and time-updated systolic BP (SBP) and diastolic BP (DBP). A composite kidney outcome of a≥50% decline in estimated glomerular filtration rate (eGFR) from the baseline value or incident kidney replacement therapy. Multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BP, respectively. During 7,472 person-years of follow-up, the primary composite kidney outcome occurred in 473 participants (23.1%), an incidence rate of 63.3 per 1,000 patient-years. Compared with baseline SBP<120mm Hg, the hazard ratios (HRs) for 120-129, 130-139, and≥140mm Hg were 1.10 (95% CI, 0.83-1.44), 1.20 (95% CI, 0.93-1.59), and 1.43 (95% CI, 1.07-1.91), respectively. This association was more evident in the model with time-updated SBP, for which the corresponding HRs were 1.31 (95% CI, 0.98-1.75), 1.59 (95% CI, 1.16-2.16), and 2.29 (95% CI, 1.69-3.11), respectively. In the analyses of DBP, we observed that time-updated DBP but not baseline DBP was significantly associated with the composite kidney outcome. Compared to patients with SBP<120mm Hg, patients with higher SBP had steeper slopes of eGFR decline. In the model including both SBP and DBP, only SBP was significantly associated with the composite kidney outcome. Observational design, unmeasured confounders, and use of office BPs only. In patients with CKD, higher SBP and DBP levels were associated with a higher risk of a composite kidney outcome reflecting CKD progression. SBP had a greater association with adverse kidney outcomes than DBP.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD.

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: NCT02165878

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

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

Left-ventricular diastolic dysfunction in Korean children with chronic kidney disease: data from the KNOW-Ped CKD study

BackgroundCardiovascular disease (CVD) is the most common cause of mortality in pediatric chronic kidney disease (CKD) patients. Left ventricular (LV) hypertrophy (LVH) is associated with LV diastolic dysfunction (LVDD) development and is used as an early marker of CVD in pediatric CKD. This study aimed to assess the prevalence and risk factors of LVDD and the association between LVH and LVDD in Korean pediatric CKD patients.MethodsData were collected using the baseline data of the Korean cohort study for outcome in patients with pediatric chronic kidney disease, a nationwide, 10-year, prospective, observational cohort study of pediatric CKD. A total of 244 patients were included in the final analysis. Two-dimensional echocardiography and tissue Doppler images were used to evaluate LVH and LVDD. LVH was defined as an LV mass index (LVMI) ≥38 g/m2.7 and LV-wall thickness z-score > 1.64. LVDD was defined as a mitral peak velocity of early filling to early diastolic mitral annular velocity (E/E’) > 14. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors of LVDD.ResultsIn this study, the male-to-female ratio was 2.2 (168:76) and median age was 11.2 years. The average estimated glomerular filtration rate was 57.4 ml/min/1.73 m2, and no patients received renal replacement therapy. The mean value of LVMI and E/E’ was 37.0 g/m2.7 and 7.4, respectively. The prevalence of LVH was 40.1 and 17.4% by LVMI ≥38 g/m2.7 and LV-wall thickness z-score, respectively. The prevalence of LVDD was 4.5%, and patients with LVH showed greater risk of LVDD (odds ratio 7.3, p = 0.012). In the univariate analysis, young age, low hemoglobin level, higher LVMI, and higher LV-wall thickness z-score were associated with LVDD. In the multivariate analysis, young age, low hemoglobin level, and higher LV-wall thickness z-score were independently associated with LVDD.ConclusionThis study shows that LVH patients have a greater risk of LVDD and that anemia is the only modifiable risk factor for LVDD in Korean pediatric CKD patients.

Low High-Sensitivity C-Reactive Protein Level in Korean Patients With Chronic Kidney Disease and Its Predictive Significance for Cardiovascular Events, Mortality, and Adverse Kidney Outcomes: Results From KNOW-CKD.

BackgroundInflammation levels are lower in East Asians than in Western people. We studied the association between high‐sensitivity hs‐CRP (C‐reactive protein) and adverse outcomes in Korean patients with chronic kidney disease.Methods and ResultsWe included 2018 participants from the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all‐cause mortality. The secondary end points were separate outcomes of eMACE, all‐cause death, and adverse kidney outcome. We also evaluated predictive ability of hs‐CRP for the primary outcome. The median hs‐CRP level was 0.60 mg/L. During the mean follow‐up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs‐CRP with the primary outcome. The hazard ratios for hs‐CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87–2.03) and 2.08 (95% CI, 1.30–3.33) compared with the hs‐CRP of <1.0 mg/L. In secondary outcomes, this association was consistent for eMACE and all‐cause death; however, hs‐CRP was not associated with adverse kidney outcomes. Finally, prediction models failed to show improvement of predictive performance of hs‐CRP compared with conventional factors.ConclusionsIn Korean patients with chronic kidney disease, the hs‐CRP level was low and significantly associated with higher risks of eMACEs and mortality. However, hs‐CRP did not associate with adverse kidney outcome, and the predictive performance of hs‐CRP was not strong.RegistrationURL: http://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Effect of urinary angiotensinogen and high-salt diet on blood pressure in patients with chronic kidney disease: results from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD).

Background/AimsThis 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.MethodsParticipants 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.ResultsElevated 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.ConclusionsUAGT 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.

The KNOW-CKD Study: What we have learned about chronic kidney diseases.

As the nation’s largest chronic kidney disease (CKD) cohort, the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was established to investigate the clinical course, risk factors for progression, and adverse outcomes of CKD. From 2011 to 2016, the KNOW-CKD recruited 2,238 adult patients with CKD from stage G1 to G5 who were not receiving renal replacement therapy from nine tertiary care hospitals throughout Korea. As of 2019, the KNOW-CKD has published more than 50 articles in the areas of socio-economics, nutrition, quality of life, health-related habits, CKD progression, cardiovascular comorbidity and outcome, anemia, mineral bone disease, biomarker discovery, and international and inter-ethnic comparisons. The KNOW-CKD will eventually offer a prediction model for long-term consequences of CKD, such as the occurrences of end-stage renal disease, cardiovascular disease, and death, thereby enabling the identification and treatment of at-risk populations that require extra medical attention.

Measured sodium excretion is associated with CKD progression: results from the KNOW-CKD study.

Diet is a modifiable factor of chronic kidney disease (CKD) progression. However, the effect of dietary salt intake on CKD progression remains unclear. Therefore, we analyzed the effect of dietary salt intake on renal outcome in Korean patients with CKD. We measured 24-h urinary sodium (Na) excretion as a marker of dietary salt intake in the prospective, multi-center, longitudinal KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD). Data were analyzed from CKD patients at Stages G3a to G5 (n = 1254). We investigated the association between dietary salt intake and CKD progression. Patients were divided into four quartiles of dietary salt intake, which was assessed using measured 24-h urinary Na excretion. The study endpoint was composite renal outcome, which was defined as either halving the estimated glomerular filtration rate or developing end-stage renal disease. During a median (interquartile range) follow-up of 4.3 (2.8-5.8) years, 480 (38.7%) patients developed the composite renal event. Compared with the reference group (Q2, urinary Na excretion: 104.2 ≤ Na excretion < 145.1 mEq/day), the highest quartile of measured 24-h urinary Na excretion was associated with risk of composite renal outcome [Q4, urinary Na excretion ≥192.9 mEq/day, hazard ratio 1.8 (95% confidence interval 1.12-2.88); P = 0.015] in a multivariable hazards model. Subgroup analyses showed that high-salt intake was particularly associated with a higher risk of composite renal outcome in women, in patients <60 years of age, in those with uncontrolled hypertension and in those with obesity. High salt intake was associated with increased risk of progression in CKD.

Mediation of the relationship between proteinuria and serum phosphate: Insight from the KNOW-CKD study.

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.

P0708ASSOCIATION OF OBESITY WITH KIDNEY CYST GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE; RESULTS FROM KNOW-CKD COHORT DATA

Abstract Background and Aims Overweight or obese patients with autosomal dominant polycystic kidney disease (ADPKD) are associated with the decline of glomerular filtration rate. However, little is known about the annual rate of change in total kidney volume (TKV) in patients with ADPKD according to the body mass index (BMI) corrected by TKV and total liver volume (TLV). Method We analyzed 364 patients with ADPKD from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease. We compared the changes in TKV in less than 1-year, 2-years and 4-year follow-up from patients by dividing baseline body mass index (BMI) by 18.5 to 22.9 (normal), 23 to 24.9 (overweight), and &amp;gt; 25 kg/m2 (obesity). Results During the 4-year follow-up period, TKV tended to increase statistically with increasing BMI (P = 0.032). Similarly, higher BMI group showed higher TKV than lower BMI group (P = 0.016). Conventional BMI is affected by TKV and TLV in advanced ADPKD patients. Therefore, we reclassified patients by corrected BMI using the adjusted body weight (body weight – TKV – TLV). Although the statistical significances between absolute value of TKV and corrected BMI groups were disappeared during the follow-up, TKV% change/year showed significantly higher in ADPKD patients with obesity among corrected BMI groups (normal; 20.2%, overweight; 17.6% and obesity; 30.6%, P for trend = 0.022) Conclusion Even after correcting the TKV and TVL, obese patients showed a high of TKV% change/year compared to non-obese patients with ADPKD.

P0850SERUM OSTEOPROTEGERIN LEVELS ARE ASSOCIATED WITH AN INCREASED RISK OF DEVELOPING ANEMIA IN PATIENTS WITH NON DIALYSIS CHRONIC KIDNEY DISEASE

Abstract 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 &amp;lt; 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.

P0881ANEMIA SIGNIFICANTLY INCREASES RISK OF OSTEOPOROSIS IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE

Abstract 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 &amp;lt; 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.

P0930SERUM LEVELS OF OSTEOPROTEGERIN ARE ASSOCIATED WITH OBESITY IN CHRONIC KIDNEY DISEASE

Abstract 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 &amp;gt;25 kg/m2 and WC &amp;gt; 90 cm in male, &amp;gt; 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&amp;lt;0.001 and OR, 0.37; 95% CI, 0.18-0.75, P=0.006, and OR, 0.33, 95% CI, 0.16-0.69, P=0.003, respectively). Among patients without baseline obesity, 207 (19.3%) patients developed obesity by BMI, 202 (21.7%) by WC, and 194 (23.3%) by composite of BMI and WC. In the fully adjusted multivariable Cox models, risks of developing obesity by BMI, WC and composite of BMI and WC were significantly higher with increased level of OPG (hazard ratio [HR], 0.59; 95% CI, 0.38-0.92; P=0.019, HR, 0.63; 95% CI, 0.41-0.98; P=0.001). Conclusion We showed that serum OPG levels are associated with obesity in patients with non-dialysis CKD.