KoreaN Cohort Study For Outcome Research Articles

Metabolic acidosis is associated with pulse wave velocity in chronic kidney disease: Results from the KNOW-CKD Study

Metabolic acidosis is common in chronic kidney disease (CKD) and may have various deleterious consequences. Arterial stiffness in CKD patients is associated with poor cardiovascular outcomes. The present study aimed to evaluate the association between serum bicarbonate and arterial stiffness using the baseline cross-sectional data set of a large-scale Korean CKD cohort. 2,238 CKD patients were enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. The present study was conducted on 1,659 patients included in this cohort with baseline serum bicarbonate and brachial-to-ankle pulse wave velocity (baPWV) data. Metabolic acidosis was defined as a serum bicarbonate level of <22 mmol/L, and baPWV was used as a surrogate of arterial stiffness. Mean serum bicarbonate was 25.8 ± 3.6 mmol/L. 210 (12.7%) patients had metabolic acidosis. baPWV was significantly higher in patients with metabolic acidosis (P < 0.001) and showed a significant inverse correlation with serum bicarbonate (Unstandardized β −16.0 cm/sec; 95% CI −20.5, −11.4; P < 0.001) in an unadjusted model, which was retained after adjustment (Unstandardized β −5.4 cm/sec; 95% CI −9.9, −1.0; P = 0.017). Metabolic acidosis was found to be associated with a high baPWV in pre-dialysis CKD patients.

Association Between High-Sensitivity Cardiac Troponin T and Echocardiographic Parameters in Chronic Kidney Disease: Results From the KNOW-CKD Cohort Study.

BackgroundIt is unclear whether high‐sensitivity troponin T (hs‐TnT) is associated with subclinical cardiac changes in chronic kidney disease (CKD). We evaluated the relationship between hs‐TnT and left ventricular structure and function in a CKD population, according to estimated glomerular filtration rate.Methods and ResultsWe analyzed 2017 patients with CKD stages 1 to 5 (predialysis) in the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) cohort. The predictor was hs‐TnT level measured at baseline, and the outcomes were left ventricular hypertrophy (LVH) and systolic and diastolic dysfunction shown by echocardiography at baseline and after 4 years. Participants were categorized into quartiles according to hs‐TnT levels. The associations between quartiles of hs‐TnT and outcomes were assessed using multivariable logistic regression analysis with confounders including demographics, medical history, and laboratory findings. A receiver operating characteristic curve was used to assess the diagnostic power of hs‐TnT for the outcomes as a continuous variable. For subgroup analysis, patients were stratified based on an estimated glomerular filtration rate of 60 mL/min per 1.73 m2. Elevated hs‐TnT was associated with LVH and diastolic dysfunction at baseline in an adjusted model but was not associated with systolic dysfunction. These associations remained significant for both estimated glomerular filtration rate subgroups. Receiver operating characteristic curve analysis showed that hs‐TnT as a continuous variable exhibited fair significance for detection of LVH (area under the curve: 0.689) and diastolic dysfunction (area under the curve: 0.744). Multivariable analysis showed that higher hs‐TnT levels at baseline were related to development of LVH but not diastolic dysfunction (n=864).ConclusionsIn CKD patients, hs‐TnT is strongly associated with alterations of left ventricular structure and diastolic dysfunction for both estimated glomerular filtration rate strata. Baseline hs‐TnT levels are predictive of new LVH on follow‐up.

Incidence of Post-transplantation Diabetes Mellitus Within 1 Year After Kidney Transplantation and Related Factors in Korean Cohort Study

BackgroundPost-transplantation diabetes mellitus (PTDM) is associated with a higher risk of mortality and graft loss. The reported incidence of PTDM after kidney transplantation (KT) varies from 10% to 74% and varies by country and ethnicity. There are few reports of nationwide cohort studies on PTDM incidence and related factors in Korea. The purpose of this study was to evaluate incidence of PTDM and related factors within 1 year after KT in Korea. MethodsThe KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) enrolled 1080 recipients from July 2012 to August 2016. This study included 723 recipients, excluding 273 patients with pretransplant DM and 84 patients who were lost from follow-up within 1 year after KT. ResultsAmong 723 recipients, 85 (11.8%) recipients were diagnosed and treated with PTDM. Recipient age, HLA mismatches, hemoglobin A1c (HbA1c), waist-hip ratio (WHR), and use of prednisolone were significantly higher in PTDM group than the nondiabetic group. In the multivariable logistic regression analysis, independent risk factors for PTDM were older recipient age, higher WHR, and HbA1c before KT. ConclusionThe incidence of PTDM was 11.8% in a nationwide Korean cohort study. The factors related to the development of PTDM within 1 year after KT were older recipient age and higher WHR, and HbA1c levels before KT. In recipients with high WHR, it is important to control pretransplant abdominal obesity to prevent PTDM after KT.

SUN-213 BONE MINERAL DENSITY AND INCIDENT END-STAGE RENAL DISEASE IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE

Despite evidences of link between mineral-bone disorder and chronic kidney disease (CKD), the relationship between bone mineral density (BMD) and end-stage renal failure (ESRD) risk is uncertain. We investigated whether BMD predicted incident ESRD in participants from The KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD).

SUN-199 URINARY ANGIOTENSINOGEN TO CREATININE RATIO (UAGT/CR) IS NOT A PREDICTIVE BIOMARKER FOR RENAL PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: KNOW-CKD STUDY

Decreased renal blood flow by cystic compression and subsequent hypertension has been suggested as one of the main mechanisms for renal progression in autosomal dominant polycystic kidney disease (ADPKD) and intrarenal renin-angiotensin-aldosterone system (RAAS) is known to play the major role in this process. Urinary angiotensinogen to creatinine ratio (UAGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAAS activity. Previous study demonstrated that ADPKD patients have 5- to 6- fold higher level of UAGT/Cr compared to non-ADPKD CKD patients and the level of UAGT/Cr was associated with decreased renal function. However, whether UAGT/Cr can predict renal function decline or kidney growth has not been elucidated. This study was performed to evaluate UAGT/Cr in a prospective ADPKD cohort and demonstrate its usefulness as a predictive biomarker in ADPKD patients. From April 2011 to February 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). UAGT was measured by commercial sandwich enzyme-linked immunosorbent assay (ELISA) (Immuno-Biological Laboratories, Co., Ltd., Gunma, Japan) and adjusted by urinary creatinine (Cr) content. Serum Cr was measured by IDMS-traceable method at a central laboratory and glomerular filtration rate (GFR) was estimated by CKD-EPI(Cr) equation. Annual GFR decline rate was calculated from the difference between final and initial Cr divided by follow-up years. Total kidney volume (TKV) was measured upon enrollment and every two years afterwards. HtTKV was calculated by TKV divided by the height of the patient. The annual eGFR decline rate and HtTKV growth rate was compared among UAGT/Cr quartile groups. The variables that do not follow normal distribution was natural log-transformed before analysis. The mean age was 47 years and male were 184 (50.5%). Most of the patients were taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers (85.9%). Baseline estimated GFR was 68.1±33.3 mL/min/1.73m2 and HtTKV was 740.7±541.6 cc/m. Mean UAGT.Cr was 16.3±45.3 μg/g. Ln(UAGT/Cr) was negatively correlated with estimated GFR (r2=0.03, p=0.001) and positively correlated with Ln(HtTKV) (r2=0.03, p=0.004). UAGT/Cr was significantly increased as CKD stage progressed (8.1±20.9 in stage 1 vs. 8.9±16.4 in stage 2 vs. 12.9±16.2 in stage 3 vs. 28.6±74.1 in stage 4 vs. 125.2±138.4 in stage 5, p<0.001). A total of 246 patients with relatively preserved GFR (>30 mL/min/1.73m2) were evaluated for the effect of UAGT/Cr upon prospective eGFR decline rate and HtTKV growth rate. The mean follow-up duration was 45.3±14.8 months. The highest quartile UAGT/Cr group showed higher systolic and diastolic blood pressure (131.9±13.6 and 83.0±10.9 mmHg, p<0.05), lower GFR at baseline (63.9±20.9 mL/min/1.73m2, p<0.001) and higher HtTKV (816.5±499.2 cc/m, p=0.079). However, neither annual GFR decline rate or HtTKV growth rate was statistically different among UAGT/Cr quartile groups. Ln(UAGT/Cr) was not associated with either annual GFR decline rate (r2=0.01, p=0.876) or Ln(HtTKV growth rate) (r2=0.036, p=0.761). UAGT/Cr is a marker of concurrent renal function and HtTKV. However, UAGT/Cr cannot predict renal progression in ADPKD.

SAT-237 PSYCHOPATHOLOGY AND PSYCHOSOCIAL ADJUSTMENT IN PEDIATRIC CHRONIC KIDNEY DISEASE: RESULTS FROM THE KNOW-Ped CKD

Chronic kidney disease (CKD) requires management in daily life; accordingly, psychosocial development of pediatric patients with CKD is greatly affected due to delayed growth, frequent absences from school, and difficulties engaging in normal activities of peer relationships due to CKD. This study was to investigate the mental health problems of children and adolescent with CKD in KoreaN cohort study for Outcome in patients with Pediatric Chronic Kidney Disease (KNOW-Ped CKD). In KNOW-PedCKD, 437 children with stage 1 to 5 of CKD were enrolled. We evaluated 167 CKD patients aged from 6-18 years (mean age, 10.6±3.9 years, male, 117 (70.1%)). Demographic data and clinical history were collected. And the parents of subject completed the Korean-Child Behavioral Checklist (K-CBCL). We compared the clinical characteristics according to the clinical group defined as one or more abnormal finding in the subscale of K-CBCL. Of the total patients, 13.2% of children had a clinically significant internalizing problem such as depression, anxiety and somatic symptoms and 9.0% of children had an externalizing problem such as rule breaking or aggressive behavior. The distribution of clinical group was 33.5% in our cohort. In the clinical group, height Z score and weight Z score were lower, and growth hormone was more used than the non-clinical group. Developmental delay and preterm birth history were more common in the clinical group. Logistic regression analysis revealed that the growth retardation and history of developmental delay was significantly correlated with the clinical group in terms of psychopathology and adjustment problem. Significant proportions of children and adolescents with CKD suffer from mental health problem and adjustment problem. Combined physical illness and growth retardation associated with CKD may be more important than CKD stage, etiology, and the complications associated with the progression of CKD in terms of mental health.

Mental health and psychosocial adjustment in pediatric chronic kidney disease derived from the KNOW-Ped CKD study.

Psychosocial development of pediatric chronic kidney disease (CKD) patients is substantially affected due to growth retardation, frequent school absences, and difficulties engaging in normal peer relationship activities. While many studies focus on specific issues such as depression, anxiety, or neurocognitive function, few evaluate prevalence of various types of mental health and psychosocial adjustment problems among children with CKD. This study aimed to investigate these within the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). One hundred sixty-six subjects who completed the Korean-Child Behavioral Checklist (K-CBCL) were included. The clinical group comprised subjects with scores indicating psychosocial adjustment or mental health problems using the T scores for the 14 subscales of the K-CBCL. We analyzed associations between mental health or adjustment problems in pediatric CKD and each variable. Mean age was 11.1 (± 3.9) years, number of males was 117 (70.5%), and 20.5% and 22.3% of children had significant mental health problems and psychosocial adjustment problems, respectively. Overall, 33.1% were assigned to the clinical group, and exhibited short stature and higher rates of preterm birth history compared to the non-clinical group. Subjects with adjustment problems had higher comorbidities such as CNS disease, developmental delay, cardiovascular disease, and multi-organ involvement. Logistic regression analysis revealed preterm birth and developmental delay correlated highly with clinical group. A significant proportion of children and adolescents with CKD experience mental health and adjustment problems. In particular, patients with developmental delay or preterm birth history require screening and targeted follow-up.

FP400SMOKING, SMOKING CESSATION, AND PROGRESSION OF CHRONIC KIDNEY DISEASE: From the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD)

FP400SMOKING, SMOKING CESSATION, AND PROGRESSION OF CHRONIC KIDNEY DISEASE: From the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD)

SP057Association between asymptomatic hyperuricemia and apparent treatment resistant hypertension in chronic kidney disease in Korea : KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD)

SP057Association between asymptomatic hyperuricemia and apparent treatment resistant hypertension in chronic kidney disease in Korea : KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD)

Hyperuricemia has increased the risk of progression of chronic kidney disease: propensity score matching analysis from the KNOW-CKD study

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

Serum klotho is inversely associated with metabolic syndrome in chronic kidney disease: results from the KNOW-CKD study

BackgroundMetabolic syndrome (MS) is prevalent in chronic kidney disease (CKD). Klotho, a protein linked to aging, is closely associated with CKD. Each component of MS and klotho has an association. However, little is known about the association between klotho and MS per se. We investigated the association between serum klotho levels and MS using baseline cross-sectional data obtained from a large Korean CKD cohort.MethodsOf the 2238 subjects recruited in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) between 2011 and 2016, 484 patients with missing data on serum klotho and extreme klotho values (values lower than the detectable range or > 6000 pg/mL) or with autosomal dominant polycystic kidney disease patients were excluded. The data of the remaining 1754 subjects were included in the present study. MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III criteria. Serum klotho levels were measured using an enzyme-linked immunosorbent assay.ResultsMean patient age was 54.9 ± 12.1 years and 1110 (63.3%) were male. The prevalence of MS among all study subjects was 63.7% (n = 1118). The median serum klotho level was 527 pg/mL (interquartile range [IQR]: 418–656 pg/mL). Serum klotho level was significantly lower in MS patients than patients without MS (Median [IQR]; 521 pg/mL [413, 651] vs. 541 pg/mL [427, 676], respectively; P = 0.012). After adjusting for age, sex, estimated glomerular filtration rate, and overt proteinuria, serum klotho was independently associated with MS (adjusted odds ratio [OR], 0.44; 95% confidence interval, 0.23–0.82; P = 0.010). Furthermore, the adjusted OR for MS was found to be significantly increased at serum klotho levels of < 518 pg/mL (receiver operating characteristic curve cut-off value).ConclusionsSerum klotho was inversely associated with the presence of MS in patients with CKD.Trial registrationThis trial was registered on ClinicalTrials.gov on 26 June 2012 (https://clinicaltrials.gov;NCT01630486).

Baseline characteristics of the autosomal-dominant polycystic kidney disease sub-cohort of the KoreaN cohort study for outcomes in patients with chronic kidney disease.

The aim of this study was to describe the baseline characteristics of autosomal-dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD). From April 2011 to February 2016, patients with CKD stage 1-5 (pre-dialysis) were enrolled as an ADPKD sub-cohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function and the factors associated with kidney function were analysed. A total of 364 ADPKD patients with a mean estimated glomerular filtration rate (eGFR) of 68.1 ± 33.3 mL/min per 1.73 m2 (50.5% male with a mean age of 47.0 ± 10.6 years) were enrolled from nine hospitals in Korea. Initially, 55.8% of the patients were asymptomatic, and pain was the most common symptom (12.9%); 87.6 and 77.5% of the patients had hypertension and hepatic cysts, respectively. The height-adjusted total kidney volumes (htTKV) were higher in male patients than in female patients. In contrast, the height-adjusted total liver volumes were higher in female patients than in male patients. The decrease rate of eGFR depending on Log(htTKV) was larger in the group aged between 41 and 50 years than the other age groups. Older age, a higher 24-h urine protein excretion, larger htTKV and hyperuricemia were independently associated with lower eGFR, whereas using febuxostat was independently associated with higher eGFR. This sub-cohort will provide clinical characteristics and outcomes of Korean ADPKD patients, which can be compared with those of other previous cohorts. We have identified factors associated with advanced-stage CKD in Korean patients with ADPKD.

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

BackgroundGuidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD.MethodsA total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline.ResultsPatients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (β = − 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07–1.55; P = 0.007).ConclusionsHigh activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.

Association Between Serum High-Density Lipoprotein Cholesterol Levels and Progression of Chronic Kidney Disease: Results From the KNOW-CKD.

BackgroundHigh‐density lipoprotein cholesterol (HDL‐C) levels are generally decreased in patients with chronic kidney disease (CKD). However, studies on the relationship between HDL‐C and CKD progression are scarce.Methods and ResultsWe studied the association between serum HDL‐C levels and the risk of CKD progression in 2168 participants of the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). The primary outcome was the composite of a 50% decline in estimated glomerular filtration rate from baseline or end‐stage renal disease. The secondary outcome was the onset of end‐stage renal disease. During a median follow‐up of 3.1 (interquartile range, 1.6–4.5) years, the primary outcome occurred in 335 patients (15.5%). In a fully adjusted Cox model, the lowest category with HDL‐C of <30 mg/dL (hazard ratio, 2.21; 95% CI, 1.30–3.77) and the highest category with HDL‐C of ≥60 mg/dL (hazard ratio, 2.05; 95% CI, 1.35–3.10) were associated with a significantly higher risk of the composite renal outcome, compared with the reference category with HDL‐C of 50 to 59 mg/dL. This association remained unaltered in a time‐varying Cox analysis. In addition, a fully adjusted cubic spline model with HDL‐C being treated as a continuous variable yielded similar results. Furthermore, consistent findings were obtained in a secondary outcome analysis for the development of end‐stage renal disease.ConclusionsA U‐shaped association was observed between serum HDL‐C levels and adverse renal outcomes in this large cohort of patients with CKD. Our findings suggest that both low and high serum HDL‐C levels may be detrimental to patients with nondialysis CKD.

Anemia and Iron Deficiency in Children with Chronic Kidney Disease (CKD): Data from the Know-Ped CKD Study.

Children with chronic kidney disease (CKD) are at high risk of anemia, an important risk factor for cardiovascular disease and poor quality of life. The present study used baseline data from the Korean cohort study for Outcome in patients With Pediatric Chronic Kidney Disease (KNOW-PedCKD). A Total of 437 patients was included in the analyses excluding missing data. The characteristics of patients with and without anemia and those of patients with and without iron deficiency were compared. Logistic regression analysis and Pearson correlation were conducted to evaluate associated risk factors and correlations in children with CKD. Anemia in children with CKD was associated with older age, low body weight and body mass index (BMI) z-score, birth age, preceding glomerulonephritis, decreased estimated glomerular filtration rate (eGFR), low levels of serum albumin and calcium, high levels of serum intact parathyroid hormone (iPTH), and serum phosphorus. Anemia was correlated positively with changes in the BMI z-score, body weight, and serum albumin and cholesterol levels, but correlated negatively with serum calcium, iPTH, ferritin levels, and transferrin saturation. Iron deficiency in children with CKD was associated with young age, low hemoglobin and serum ferritin levels, high BMI z-scores, and low levels of serum iPTH. This is the first nationwide cohort study of anemia in Korean children with CKD and the first prospective pediatric CKD cohort study in Asia. The study results demonstrated that anemia and iron deficiency are affected by various factors, including age, BMI, and levels of serum iPTH. To improve the retrospective outcome of affected children, it is important to understand the effect of each of these factors and to attempt an early intervention to prevent anemia and iron deficiency by regular measurement of these parameters in children at risk.

The effect of interactions between proteinuria, activity of fibroblast growth factor 23 and serum phosphate on renal progression in patients with chronic kidney disease: a result from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease study.

Recent experimental study reported that proteinuria increases serum phosphate by decreasing biologic activity of fibroblast growth factor 23 (FGF-23). We examined this relationship in a large chronic kidney disease (CKD) cohort and evaluated the combined effect of proteinuria, FGF-23 activity and serum phosphate on CKD progression. The activity of FGF-23, measured by the fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria in 1909 patients with CKD. Primary outcome was CKD progression defined as ≥50% decline of estimated glomerular filtration rate, doubling of serum creatinine and start of dialysis. There was a negative relationship between 24-h urine protein (24-h UP) and FEP/FGF-23 ratio (γ -0.07; P = 0.005). In addition, after matching variables associated with serum phosphate, patients with more proteinuria had higher serum phosphate (P < 0.001) and FGF-23 (P = 0.012), and lower FEP/FGF-23 ratio (P = 0.007) compared with those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was an independent risk factor for CKD progression (hazard ratio 0.87 per 1 log increase; 95% confidence interval 0.79-0.95; P = 0.002), and there was significant interaction between 24-h UP and FEP/FGF-23 ratio (P = 0.039). Furthermore, 24-h UP and serum phosphate also had a significant interaction on CKD progression (P < 0.001). Proteinuria is associated with decreased biologic activity of FGF-23 and increased serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.

Body Mass Index, waist circumference, and health-related quality of life in adults with chronic kidney disease.

Obesity is linked to poor health-related quality of life (HRQOL) in the general population, but its role in chronic kidney disease (CKD) is uncertain. We conducted a cross-sectional study that investigated 1880 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) who underwent complete baseline laboratory tests, health questionnaires, and HRQOL. HRQOL was assessed by physical component summary (PCS) and mental component summary (MCS) of the SF-36 questionnaire. We used multivariable linear regression models to examine the relationship between Body Mass Index (BMI) and sex-specific waist circumference (WC) with HRQOL. Adults with higher BMI and greater WC showed lower PCS. After adjusting for age, sex, socioeconomic state, comorbidities, and laboratory findings, we found that WC, but not BMI, was associated with PCS. Greater WC quintiles were associated with lower PCS [WC-4th quintile (β, - 2.63, 95% CI - 5.19 to - 0.06) and WC-5th quintile (β, - 3.71, 95% CI - 6.28 to - 1.15)]. The association between WC and PCS was more pronounced in older adults, woman, patients with diabetes, cardiovascular disease, or lower eGFR. The relationship between BMI and WC with MCS was not significant. In adults with CKD, WC is a better indicator of poor physical HRQOL than BMI. The association between WC and physical HRQOL is modified by age, sex, eGFR, and comorbidities such as diabetes and cardiovascular disease.

The ratio of urinary sodium and potassium and chronic kidney disease progression: Results from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD).

The Na/K ratio in urine stands for the dietary of sodium and potassium intake in patients with chronic kidney disease remains unclear for the renal progression. We aimed to determine the risk of progression of chronic kidney disease based on the Na/K ratio in a 24-hour urine collection.We determined the association between the progression of renal disease and 24-hour urinary sodium and potassium (Na/K) ratios in 2238 patients over a 5-year timespan using data obtained from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). Renal events were defined as a 50% decrease in the glomerular filtration rate (GFR) below baseline, or the onset of end-stage renal disease (ESRD). Patients were divided into 4 groups based on the quartile range of the 24-hour urinary sodium and potassium ratio. We analyzed those variables in the 4 groups. Multiple logistic regression analyses were performed using the data of 1001 patients to identify the independent factors associated with renal events.Age and male sex accounted for the greatest number of patients in the group with the highest values (group 4) of the 24-hour urinary Na/K ratio (≥3.85). There was no difference in the prevalence of hypertension or diabetes mellitus, the ratio of use of antihypertensive drugs, blood pressures, or estimated GFRs. In the group with the highest urinary Na/K ratio, the 24-hour urinary Na concentration mean ± standard deviation was 188.7 ± 70.6 mmol and that of urinary K was 39.9 ± 16.1 mmol. The urinary protein excretion was highest in the group with the highest urinary Na/K ratio. In the logistic regression analysis, the effect on renal events increased with increasing urinary Na/K ratios. After adjusting for other factors, the risk of renal events was 2.48 (95% confidence interval (CI) 1.30–4.90) in group 3, and 3.75 (95% CI: 1.35–11.27) in group 4. In the Kaplan–Meier analysis, the higher the urinary Na/K ratio, the higher the rate of CKD progression.Based on our analyses, we concluded that the higher the urinary Na/K ratio, the greater the risk of CKD progression.

The association between socioeconomic disparities and left ventricular hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

BackgroundLeft ventricular hypertrophy (LVH) is one of the risk factors for cardiovascular (CV) disease and mortality. However, the relationship between socioeconomic status (SES) and LVH in chronic kidney disease remains unclear.MethodsData were collected from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at http://www.clinicaltrials.gov). Subjects with CKD and aged ≥50 were included. SES was characterized based on monthly income and educational attainment, each of which was divided into three strata. LVH was defined as LV mass/height2.7 ≥ 47 g/m2.7 in female and ≥ 50 g/m2.7 in male. Age, sex, diabetes, CKD stage, body mass index, blood pressure and physical activity were included as covariates.ResultsA total of 1361 patients were included. Mean age was 60.9 ± 6.9 years, and 63.2% were men. Higher education level was associated with higher monthly income (P for trend < 0.001). The lowest education level was independently associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95% CI 1.069–2.063, P = 0.018; completed high school, adjusted OR 1.150, 95% confidence interval [CI] 0.834–1.584, P = 0.394; highest education level as the reference). Monthly income level was marginally associated with LVH after adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866–1.748, P = 0.247; < $1500, adjusted OR 1.471, 95% CI 1.002–2.158, P = 0.049; > $4500; reference).ConclusionsIn the CKD population, lower SES, defined by educational attainment and low income level exhibited a significant association with LVH, respectively. Longitudinal follow-up will reveal whether lower SES is associated with poor CKD outcomes.

Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Fibroblast growth factor-23 (FGF23) is an established biomarker of adverse outcomes in patients with chronic kidney disease (CKD). Several cross-sectional studies have suggested a possible association between FGF23 and anemia in these patients. In this large-scale prospective cohort study, we investigated this relationship and examined whether high FGF23 levels increase the risk of incident anemia. This prospective longitudinal study included 2,089 patients from the KoreaN cohort study for Outcome in patients With CKD. Anemia was defined as hemoglobin level <13.0 g/dl (men) and <12.0 g/dl (women). Log-transformed FGF23 significantly correlated with hepcidin but inversely correlated with iron profiles and hemoglobin. Multivariate logistic regression showed that log-transformed FGF23 was independently associated with anemia (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04–1.24, P = 0.01). Among 1,164 patients without anemia at baseline, 295 (25.3%) developed anemia during a median follow-up of 21 months. In fully adjusted multivariable Cox models, the risk of anemia development was significantly higher in the third (hazard ratio [HR], 1.66; 95% CI, 1.11–2.47; P = 0.01) and fourth (HR, 1.84; 95% CI, 1.23–2.76; P = 0.001) than in the first FGF23 quartile. In conclusion, high serum FGF23 levels were associated with an increased risk for anemia in patients with nondialysis CKD.