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.ope

Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy

BACKGROUND: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. METHODS: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. RESULTS: Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37-0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43-0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44-0.97; P = 0.03). CONCLUSION: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.ope

Neck circumference predicts renal function decline in overweight women: A community-based prospective cohort study

Chronic kidney disease (CKD) is characterized by increased risks of morbidity and mortality. Upper-body subcutaneous fat, which is commonly estimated from the neck circumference (NC), was revealed to be the main reservoir of circulating nonesterified fatty acids in overweight patients. Despite a close association between NC and metabolic complications, the relationship of NC with renal function has not been fully investigated. In this study, the impact of NC on the development of incident CKD was elucidated.The data were retrieved from the Korean Genome and Epidemiology Study cohort. The subjects were followed at 2-year intervals from 2003 to 2011. Overweight was defined as a body mass index of ≥23?kg/m. A total of 4298 cohort subjects were screened. After exclusion, 2268 overweight subjects were included for the final analysis. The primary end point was incident CKD, which was defined as a composite of estimated glomerular filtration rate (eGFR)?<?60?mL/min/1.73?m or the development of proteinuria.The mean patient age was 36.3?±?3.0 years, and 1285 (56.7%) were men. They were divided into 2 groups according to the median NC in male and female subjects, separately. In both sexes, hypertension (men, P?<?0.001; women, P = 0.009) and diabetes (men, P = 0.002; women, P?<?0.001) were significantly more prevalent in the big NC group than in the small NC group. In contrast, eGFR was significantly lower only in male subjects of the big NC group (P?<?0.001), whereas it was comparable between the small and big NC groups (P = 0.167). In multivariate Cox proportional hazards regression analysis, NC values were independently associated with incident CKD development in female subjects after adjusting for multiple confounding factors (per 1?cm increase, hazard ratio [95% confidence interval] = 1.159 [1.024-1.310], P = 0.019) but not in male subjects.NC is independently associated with the development of CKD in overweight female subjects, suggesting that it could be a practical risk factor for CKD.ope

The impact of disease severity on paradoxical association between body mass index and mortality in patients with acute kidney injury undergoing continuous renal replacement therapy

BACKGROUND: Association between high body mass index (BMI) and survival benefit is confounded by comorbid conditions such as nutritional status and inflammation. Patients with acute kidney injury (AKI), particularly those receiving continuous renal replacement therapy (CRRT), are highly catabolic and more susceptible to loss of energy. Herein, we evaluated whether disease severity can modify the relationship between BMI and mortality. METHODS: We conducted an observational study in 1144 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. Patients were categorized into four groups; underweight (/=25 kg/m(2)) according to BMI classification by the Committee of Clinical Practice Guidelines and Korean Society for the Study of Obesity. More severe disease was defined as sepsis-related organ failure assessment (SOFA) score of >/= a median value of 12. The study endpoint was death that occurred within 30 days after the initiation of CRRT. RESULTS: The mean age was 63.2 years and 439 (38.4%) were females. The median BMI was 23.6 (20.9-26.2) kg/m(2). The obese group were younger and higher SOFA score than normal BMI group. In a multivariable Cox regression analysis, we found a significant interaction between BMI and SOFA score (P < 0.001). Furthermore, obese patients were significantly associated with a lower risk of death as compared to normal BMI group after adjusting confounding factors [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.68-0.97; P = 0.03]. This association was only evident among patients with high severity (HR, 0.61; 95% CI, 0.48-0.76, P < 0.001). In contrast, in those with low severity, survival benefit of high BMI was lost, whereas underweight was associated with an increased risk of death (HR, 1.74; 95% CI, 1.16-2.60; P = 0.007). CONCLUSION: In this study, we found a survival benefit of high BMI in AKI patients undergoing CRRT, particularly in those with more disease severity; the effect was not observed in those with less disease severity.ope

THYROID HORMONE REPLACEMENT REDUCES THE RISK OF CARDIOVASCULAR DISEASES IN DIABETIC NEPHROPATHY PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM

OBJECTIVE: Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. METHODS: This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. RESULTS: Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 +/- 12.3 and 66.8 +/- 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 +/- 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. CONCLUSION: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. ABBREVIATIONS: CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.restrictio

Severe vitamin D deficiency is a risk factor for renal hyperfiltration

Background: Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population. Objective: We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population. Design: Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration 95th percentile after adjustment for age, sex, height, weight, and history of hypertension or diabetes. Results: The mean ± SD age of subjects was 48.1 ± 15.9 y, and the number of women was 18,779 (56.5%). Estimated glomerular filtration rate was negatively associated with serum 25-hydroxyvitamin D concentrations in multivariable linear regression analysis (β: -0.02; 95% CI: -0.02, -0.01; P < 0.001). Furthermore, 1637 (4.9%) subjects were categorized into the RHF group, and the prevalence of RHF was significantly higher in the severe vitamin D deficiency group than in the sufficiency group (5.8% compared with 5.0%, P < 0.001). In a multivariable logistic regression model, severe vitamin D deficiency was a significant risk factor for RHF (OR: 2.41; 95% CI, 1.72, 3.43; P < 0.001). Conclusions: Severe vitamin D deficiency is significantly associated with increasing prevalence of RHF in a relatively healthy adult population.restrictio

Microscopic hematuria is a risk factor of incident chronic kidney disease in the Korean general population: a community-based prospective cohort study

Background: Although asymptomatic microscopic hematuria (MH) is a common finding in clinical practice, its long-term outcome remains unknown. Aim: This study evaluated the clinical implication of MH in the general population using a large-scale long-term longitudinal cohort database. Methods: This study included 8719 participants from the Korean Genome and Epidemiology Study between 2001 and 2014. MH was defined as ≥5 red blood cells per high-power field in random urinalysis without evidence of pyuria. The primary study outcome measure was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate <60 ml min-1⋅1.73⋅m-2. Results: During a median follow-up of 11.7 years, CKD occurred in 677 (7.8%) subjects. In Cox regression after adjustment for multiple confounders, subjects with MH had a significantly higher risk of incident CKD than those without [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.12-1.87; P = 0.005]. Isolated MH without proteinuria was also a risk factor of incident CKD (HR 1.37, 95% CI 1.04-1.79; P = 0.023) and the risk was further increased in MH with concomitant proteinuria (HR 5.41, 95% CI 2.54-11.49; P < 0.001). In propensity score matching analysis after excluding subjects with proteinuria, multi-variable stratified Cox regression analysis revealed that subjects with isolated MH had a significantly higher risk of incident CKD than those without (HR 1.83, 95% CI 1.14-2.94; P = 0.012). Conclusion: The presence of MH is associated with an increased risk of incident CKD in the general population. Therefore, attentive follow-up is warranted in persons with MH for early detection of CKD.restrictio

High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension

The association between salt intake and renal outcome in subjects with preserved kidney function remains unclear. Here we evaluated the effect of sodium intake on the development of chronic kidney disease (CKD) in a prospective cohort of people with normal renal function. Data were obtained from the Korean Genome and Epidemiology Study, a prospective community-based cohort study while sodium intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A total of 3,106 individuals with and 4,871 patients without hypertension were analyzed with a primary end point of CKD development [a composite of estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m(2) and/or development of proteinuria during follow-up]. The median ages were 55 and 47 years, the proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73 m(2) in individuals with and without hypertension, respectively. During a median follow-up of 123 months in individuals with hypertension and 140 months in those without hypertension, CKD developed in 27.8% and 16.5%, respectively. After adjusting for confounders, multiple Cox models indicated that the risk of CKD development was significantly higher in people with hypertension who consumed less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between 2.93-4.03 g/day sodium. However, there was no significant difference in the incident CKD risk among each quartile of people without hypertension. Thus, both high and low sodium intakes were associated with increased risk for CKD, but this relationship was only observed in people with hypertension.restrictio

Effects of Coffee Intake on Incident Chronic Kidney Disease: A Community-Based Prospective Cohort Study

BACKGROUND: Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population. METHODS: We analyzed 8717 subjects with normal renal function recruited from the Korean Genome and Epidemiology Study (KoGES) cohort. Based on a food frequency questionnaire, coffee consumption was categorized into 5 groups: 0 per week, <1 cup per week, 1-6 cups per week, 1 cup per day, and ≥2 cups per day. The primary outcome was incident chronic kidney disease, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: The mean age (standard deviation) of study subjects was 52.0 (8.8) years, and 47.8% were male. Among the subjects, 52.8% were daily coffee consumers. During a mean follow-up of 11.3 (range, 5.9-11.5) years, 9.5% of participants developed chronic kidney disease. The incident chronic kidney disease occurred less in daily coffee consumers. Unadjusted hazard ratios (HRs) was significantly lower in daily coffee consumers. In multivariable Cox model even after adjustment of blood pressure, hypertension, cardiovascular disease, diabetes, and amount of daily intake for caffeine-containing foods such as tea and chocolate, coffee consumers with 1 cup per day (HR, 0.76; 95% confidence interval, 0.63-0.92) and ≥2 cups per day (HR, 0.80; 95% confidence interval, 0.65-0.98) were associated with a lower risk of chronic kidney disease development than nondrinkers. Time-averaged and time-varying Cox models yielded similar results. The rates of decline in glomerular filtration were lower in daily coffee consumers. CONCLUSIONS: Our findings suggest that daily coffee intake is associated with decreased risk of the development of chronic kidney disease.restrictio

High dietary phosphorus density is a risk factor for incident chronic kidney disease development in diabetic subjects: a community-based prospective cohort study

Background: High serum phosphorus concentrations are associated with an increased risk of cardiovascular disease and progression of chronic kidney disease (CKD). However, the relation between dietary phosphorus intake and CKD development has not been well evaluated.Objective: In this study, we investigated the impact of dietary phosphorus density on the development of incident CKD in a cohort of subjects with normal renal function.Design: Data were retrieved from the Korean Genome and Epidemiology Study, a prospective community-based cohort study. The study cohort consisted of subjects aged 40-69 y, who were followed up biennially from 2001 to 2014. A total of 873 subjects with diabetes mellitus (DM) and 5846 subjects without DM (non-DM) were included in the final analysis. The primary endpoint was incident CKD, defined as a composite of estimated glomerular filtration rate <60 mL · min-1 · 1.73 m-2 and/or the development of proteinuria.Results: In the DM and non-DM groups, the mean ages of the participants were 55.6 ± 8.7 and 51.4 ± 8.6 y, the numbers of male subjects were 454 (52.0%) and 2784 (47.6%), and the mean estimated glomerular filtration rates were 91.6 ± 14.0 and 94.5 ± 14.0 mL · min-1 · 1.73 m-2, respectively. The mean values of dietary phosphorus density, defined as the ratio of a single-day dietary phosphorus amount to the total daily calorie intake, were 0.51 ± 0.08 mg/kcal in the DM group and 0.51 ± 0.07 mg/kcal in the non-DM group. During the follow-up, CKD newly developed in 283 (32.4%) and 792 subjects (13.5%) in the DM and non-DM groups, respectively. When the subjects were divided into quartiles according to the dietary phosphorus density in each group, the highest quartile was significantly associated with the development of incident CKD by multiple Cox proportional hazard analysis in the DM group (P = 0.02) but not in the non-DM group (P = 0.72).Conclusions: High dietary phosphorus density is associated with an increased risk of CKD development in DM patients with normal renal function. The causality in this association needs to be tested in a randomized controlled trial.restrictio