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Background Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD) and in the general population. However, few studies have investigated risk factors for bone loss in patients with CKD. The aim of this study was to investigate whether renal function is associated with the rate of BMD decline. Methods A prospective cohort study included 1006 patients with CKD stages 2–4 between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and 4 years. The eGFR was measured 2–6 times during the 4-year follow-up. We analyzed the decline in bone mineral density according to CKD stage and further compared the rate of BMD decline according to eGFR trajectories at each stage. Results Advanced CKD stage was associated with a faster rate of decline in total hip BMD [stage 2 −0.23, stage 3A −0.39, stage 3B −0.80, stage 4 −1.23% change/year in men (P < .001); stage 2 −0.86, stage 3A −1.19, stage 3B −1.20, stage 4 −1.58% change/year in women (P  < .03)]. Two distinct eGFR trajectories (Class 1 stable group; Class 2 rapid decline group) were observed. The rapid decline group showed a trend toward an increased rate of decline in total hip BMD. Subgroup analysis according to eGFR trajectories revealed a significant difference in BMD decline rate between stable and rapid decline groups. Conclusions Advanced CKD stage and accelerated decline in renal function were associated with rapid BMD decline in non-dialysis patients with CKD. [ABSTRACT FROM AUTHOR]

Background Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. Methods From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1–5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). Results The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. Conclusions The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients. [ABSTRACT FROM AUTHOR]

Background: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. Methods: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow‐up period. Results: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person‐years of follow‐up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person‐years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause‐specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60–0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13–1.64) for BP above both targets, compared with BP controlled within 2012 target only. Conclusion: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline. [ABSTRACT FROM AUTHOR]

Background In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus the clinical predictive performance of well-known risk factors warrants further testing in this population. Methods The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1–G5 without kidney replacement therapy between 2011 and 2016. The main predictor was the coronary artery calcium score (CACS). The primary outcome was a composite of nonfatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACEs; the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), all CVEs and all-cause mortality. Results During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate 1.6/100 person-years). In the multivariable Cox model, a 1-standard deviation log increase in the CACS was associated with a 1.67-fold [95% confidence interval (CI), 1.37–2.04] higher risk of the primary outcome. Compared with a CACS of 0, the hazard ratio associated with a CACS >400 was 4.89 (95% CI 2.68–8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, inclusion of the CACS led to modest improvements in prediction indices of the primary outcome compared with well-known conventional risk factors. Conclusions In Korean patients with CKD, the CACS was independently associated with adverse cardiovascular outcomes and all-cause death. The CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Although cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death. This was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of β-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome. During a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7 % [adjusted hazard ratio (aHR), 1.07; 95 % confidence interval (CI), 1.05–1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95 % CI) for Q4 versus Q1 was 1.18 (1.11–1.27). This association was consistent for incident CKD (aHR, 1.04; 95 % CI, 1.01–1.07), and all-cause mortality (aHR, 1.10; 95 % CI, 1.07–1.13). Compared with Q1, Q4 was associated with a 12 % (aHR 1.12; 95 % CI 1.02–1.24) and 26 % (aHR 1.26; 95 % CI 1.15–1.37) higher risk of incident CKD and all-cause mortality, respectively. Higher KB levels were independently associated with higher risk of incident CKD and death. [ABSTRACT FROM AUTHOR]

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

Background Although it is well known that low bone mineral density (BMD) is associated with an increased risk of cardiovascular disease (CVD) and mortality in the general population, the prognostic role of bone mineral density (BMD) has not been established in the chronic kidney disease (CKD) population. Therefore we aimed to evaluate the association between BMD and the risk of CVD and cardiovascular mortality in patients with predialysis CKD. Methods This prospective cohort study was conducted with 1957 patients with predialysis CKD Stages 1–5. BMD was measured using dual-energy X-ray absorptiometry and coronary arterial calcification (CAC) scores were evaluated using coronary computed tomography. The primary outcome was a major adverse cardiovascular event (MACE). Results When patients were classified based on total hip BMD T -score tertiles stratified by sex, the lowest BMD tertile was significantly associated with an increased risk of MACE {hazard ratio 2.16 [95% confidence interval (CI) 1.25–3.74]; P = 0.006}. This association was also shown with BMD at the femur neck but not with BMD at lumbar spine. In the subgroup of 977 patients with follow-up CACs at their fourth year, 97 (9.9%) showed accelerated CAC progression (>50/year), and BMD was inversely associated with accelerated CAC progression even after adjusting for the baseline CAC score [odds ratio 0.75 (95% CI 0.58–0.99); P = 0.039]. In addition, baseline CAC was associated with an increased risk of MACEs after adjusting for total hip T -score. Conclusions Low BMD was significantly associated with CAC progression and MACEs in patients with predialysis CKD. [ABSTRACT FROM AUTHOR]

BACKGROUND Although abnormal blood pressure (BP) patterns are associated with adverse cardiorenal outcomes, their associations are yet unquantified by nocturnal dipping status. We examined the association of nocturnal BP dipping pattern with albuminuria and kidney function among participants with controlled hypertension without prior advanced kidney disease. METHODS Ambulatory BP (ABP) measurements were collected from 995 middle-aged, cardiology clinic patients with controlled office BP (OBP) (<140/90 mm Hg). The magnitude of dipping was calculated as the difference between daytime and nighttime systolic BP (SBP) divided by daytime SBP. Accordingly, the participants were categorized as extreme-dipper (≥20%), dipper (10% to <20%), non-dipper (0% to <10%), or reverse-dipper (<0%). We analyzed the cross-sectional associations of dipping with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and decreased estimated glomerular filtration rate (<60 ml/min/1.73 m2), adjusting for OBP/ABP, antihypertensive class, body mass index, total cholesterol, fasting glucose, socioeconomic status, and health behavior. RESULTS The participants (mean age 60.2 years; 52.9% male) consisted of 13.5% extreme-dippers, 43.1% dippers, 34.7% non-dippers, and 8.7% reverse-dippers. In reference to dippers, odds ratios [95% confidence interval] for albuminuria were 1.73 [1.04–2.60] in reverse-dippers, 1.67 [1.20–2.32] in non-dippers, and 0.62 [0.38–1.04] in extreme-dippers. Likewise, abnormal dipping profile was associated with decreased kidney function: reverse-dipping, 2.02 [1.06–3.84]; non-dipping, 1.98 [1.07–3.08]; extreme-dipping, 0.69 [0.20–1.17]. The associations persisted among participants with more conservatively controlled OBP (<130/80 mm Hg). CONCLUSIONS Monitoring diurnal and nocturnal BP may identify chronic kidney disease otherwise overlooked based on OBP. [ABSTRACT FROM AUTHOR]

Previous studies have shown that dietary zinc intake is closely related to cardiovascular complications and metabolic derangements. However, the effect of dietary zinc intake on renal function is not fully elucidated. Data from the Korean Genome and Epidemiology Study were used. Dietary zinc intake was assessed by a Food Frequency Questionnaire and dietary zinc density was calculated as absolute zinc intake amount per daily energy intake (mg/1000 kcal day). The participants were categorized into quartiles according to dietary zinc density. The primary end point was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. A total of 7735 participants with normal renal function was included in the final analysis. The mean age was 52.0 ± 8.8 years, 47.5% were male, and mean eGFR was 92.1 ± 16.1 ml/min/1.73 m2. The mean daily zinc intake and zinc intake density were 8.6 ± 3.4 mg and 4.4 ± 0.9 mg/1000 kcal, respectively. During a median follow up of 11.5 (1.7–12.5) years and 70,617 person-years of observation, CKD developed in 1409 (18.2%) participants. Multivariable cox hazard analysis revealed that risk for CKD development was significantly higher in the quartile with a mean zinc intake density of 3.6 ± 0.2 mg/1000 kcal compared with the quartile with a mean zinc intake density of 5.6 ± 1.0 mg/1000 kcal (Hazard ratio; 1.36; 95% Confidence Interval 1.18–1.58; P < 0.001). This relationship remained significant even after adjustments for confounding factors. Low dietary zinc intake may increase the risk of CKD development in individuals with normal renal function. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Conclusions High salt intake was associated with increased risk of progression in CKD. [ABSTRACT FROM AUTHOR]

Background: Obesity, a known risk factor for chronic kidney disease (CKD), is generally assessed using body mass index (BMI). However, BMI may not effectively reflect body composition, and the impact of muscle‐to‐fat (MF) mass balance on kidney function has not been elucidated. This study evaluated the association between body muscle and fat mass balance, represented as the MF ratio, and incident CKD development. Methods: Data were retrieved from a prospective community‐based cohort study (Korean Genome and Epidemiology Study). Muscle and fat mass were measured using multifrequency bioelectrical impedance analysis. The study endpoint was incident CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 in at least two or more consecutive measurements during the follow‐up period). Results: Totally, 7682 participants were evaluated. Their mean age was 51.7 ± 8.7 years, and 48% of the subjects were men. During a median follow‐up of 140.0 (70.0–143.0) months, 633 (8.2%) subjects developed incident CKD. When the association between body composition and incident CKD was investigated, multivariable Cox proportional hazard analysis revealed that increase in MF ratio was related with a decreased risk of CKD development [per 1 increase in MF ratio: hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.77–0.96; P = 0.008]. This association was also maintained when MF ratio was dichotomized according to sex‐specific median values (high vs. low: HR, 0.83; 95% CI, 0.70–0.98; P = 0.031). Analyses preformed in a propensity score matched group also revealed a similar decreased risk of incident CKD in high MF ratio participants (high vs. low: HR, 0.84; 95% CI, 0.71–0.98; P = 0.037). This relationship between MF ratio and incident CKD risk was consistently significant across subgroups stratified by age, sex, hypertension, estimated glomerular filtration rate categories, and proteinuria. Among different BMI groups (normal, overweight, and obese), the relationship between high MF ratio and lower incident CKD risk was significant only in overweight and obese subjects. Conclusions: Lower fat mass relative to muscle mass may lower the risk of CKD development in individuals with normal renal function. This relationship seems more prominent in overweight and obese subjects than in normal weight subjects. [ABSTRACT FROM AUTHOR]

Background: Urine osmolality indicates the ability of the kidney to concentrate the urine and reflects the antidiuretic action of vasopressin. However, results about the association between urine osmolality and adverse renal outcomes in chronic kidney disease (CKD) are conflicting. We investigated the association between urine osmolality and adverse renal outcomes in a nationwide prospective CKD cohort. Methods: A total of 1,999 CKD patients were categorized into 3 groups according to their urine osmolality tertiles. Primary outcome was a composite of 50% decline in the estimated glomerular filtration rate (eGFR), initiation of dialysis, or kidney transplantation. Results: During a mean follow-up of 35.2 ± 19.0 months, primary outcome occurred in 432 (21.6%) patients; 240 (36.4%), 162 (24.3%), and 30 (4.5%) in the lowest, middle, and highest tertiles, respectively. Low urine osmolality was independently associated with a greater risk of CKD progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12–2.59). This association was particularly evident in patients with CKD stages 3–4 (per 10 mosm/kg decrease; HR, 1.02; 95% CI, 1.00–1.03). Adding urine osmolality to a base model with conventional factors significantly increased the ability to predict CKD progression (C-statistics, 0.86; integrated discrimination improvement [IDI], 0.021; both p < 0.001). However, adding both urine osmolality and eGFR did not further improve the predictive ability compared with the addition of eGFR only (C-statistics, p = 0.29; IDI, p = 0.09). Conclusions: Low urine osmolality was an independent risk factor for adverse renal outcomes in CKD patients, but its predictive ability did not surpass eGFR. Thus, kidney function should be considered while interpreting the clinical significance of urine osmolality. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between metabolically healthy obese (MHO) phenotype and incident chronic kidney disease (CKD) and study whether changes in metabolic phenotypes over time could affect CKD risk. Methods: A total of 8589 subjects from the Korean Genome and Epidemiology Study were categorized into four groups based on the presence of obesity and metabolic abnormalities (MA). The primary endpoint was an onset of incident CKD defined as an estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m2. Multivariable Cox analysis and time‐varying Cox analysis were performed to delineate the relationship between obese metabolic phenotypes and incident CKD after adjustment for sociodemographic factors and clinical and laboratory parameters. Results: During a mean follow‐up duration of 9.3 years, CKD occurred in 782 (9.1%) participants. In the multivariable Cox model, the hazard ratio (HR) for incident CKD in the MHO, metabolically abnormal non‐obese (MANO), and metabolically abnormal obese (MAO) groups was 1.42 (P = 0.002), 1.45 (P < 0.001), and 1.77 (P < 0.001), respectively, compared with the metabolically healthy non‐obese (MHNO) group. Time‐varying analysis with these four phenotypes as time‐varying exposures showed the same results. Furthermore, subjects with persistent MHO through follow‐up were at a 2.0‐fold increased risk of CKD (P < 0.001). 41.0% of subjects experienced phenotype changes during follow‐up. Over the long term, the MHO group had a higher proportion of transition to the MA phenotype and unfavourable metabolic profiles than the MHNO group. Among MHO subjects, those who transitioned to MAO were at a 4.1‐fold increased risk of incident CKD than those who regressed to MHNO. In addition, transition to MHO from other groups carried a higher risk of CKD than persistent MHNO. Conclusion: MHO subjects are at increased risk for incident CKD. [ABSTRACT FROM AUTHOR]

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 <10 ng/mL. RHF was defined as estimated glomerular filtration rate with residual in the >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. [ABSTRACT FROM AUTHOR]

Hyperphosphatemia is associated with mortality in patients with chronic kidney disease, and is common in critically ill patients with acute kidney injury (AKI); however, its clinical implication in these patients is unknown. We conducted an observational study in 1144 patients (mean age, 63.2 years; male, 705 [61.6%]) with AKI who received continuous renal replacement therapy (CRRT) between January 2009 and September 2016. Phosphate levels were measured before (0 h) and 24 h after CRRT initiation. We assessed disease severity using various clinical parameters. Phosphate at 0 h positively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II; P < 0.001) and Sequential Organ Failure Assessment (SOFA; P < 0.001) scores, and inversely with mean arterial pressure (MAP; P = 0.02) and urine output (UO; P = 0.01). In a fully adjusted linear regression analysis for age, sex, Charlson comorbidity index (CCI), MAP, and estimated glomerular filtration rate (eGFR), higher 0 h phosphate level was significantly associated with high APACHE II (P < 0.001) and SOFA (P = 0.04) scores, suggesting that phosphate represents disease severity. A multivariable Cox model also showed that hyperphosphatemia was significantly associated with increased 28-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) and 90-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) mortality. Furthermore, patients with increased phosphate level during 24 h were at higher risk of death than those with stable or decreased phosphate levels. Finally, c-statistics significantly increased when phosphate was added to a model that included age, sex, CCI, body mass index, eGFR, MAP, hemoglobin, serum albumin, C-reactive protein, and APACHE II score. This study shows that phosphate is a potential biomarker that can reflect disease severity and predict mortality in critically ill patients receiving CRRT. [ABSTRACT FROM AUTHOR]

Background: The atherogenic index of plasma (AIP), which is the logarithmic ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C), had a linear relationship with clinical outcomes in the general population. However, the association of each lipid profile, TG and HDL-C, with survival was not straightforward in dialysis patients. This non-linear association led us to further investigate the prognostic impact of the AIP in these patients. Methods: From a nationwide prospective cohort, 1,174 incident dialysis patients were included. Patients were categorized into quintiles according to the AIP. An independent association of the AIP with all-cause and cardiovascular mortality was determined. Results: During a mean follow-up duration of 33.2 months, 170 patients (14.5%) died, and cardiovascular death was observed in 55 patients (4.7%). Multivariate Cox analyses revealed that the lowest (quintile 1, hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.02–3.03) and the highest (quintile 5, HR = 2.15, 95% CI = 1.26–3.65) AIP groups were significantly associated with higher all-cause mortality compared to patients in quintile 3 (reference group). In terms of cardiovascular mortality, only the highest AIP group (quintile 5, HR = 2.59, 95% CI = 1.06–6.34) was significantly associated with increased risk of mortality. Sensitivity analyses showed that a U-shaped association between the AIP and all-cause mortality remained significant in non-diabetic and underweight to normal body mass index patients. Conclusions: Both the highest and the lowest AIP groups were independently associated with all-cause mortality, showing a U-shaped association. It suggested further studies are needed to identify targets and subgroups that can benefit from intervention of the AIP in incident dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Depression is reported to be the most common psychological problem in patients with chronic kidney disease (CKD). Several studies have reported that lower levels of serum vitamin D are significantly associated with depression. Both vitamin D deficiency and depression are prevalent in patients with CKD, yet the relationship between these two factors remains poorly understood. This study aimed to investigate the association between vitamin D levels and depression among CKD patients. Methods: Totally, 21,257 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES V, VI) from 2010–2014 were screened for the study; 533 CKD patients were included. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D3 [25(OH)D3] ≤10 ng/mL. Patients were divided into vitamin D deficient or sufficient groups. Depression was screened for using the Korean version of the WHO Composite International Diagnostic Interview-Short Form. The association between vitamin D deficiency and depression was evaluated by multivariate logistic regression analysis. Results: The mean participant age was 70.1±9.4 years; 262 patients (49.2%) were male. The median 25(OH)D3 level was 19.1±6.9 ng/mL. The prevalence of depression was higher in CKD patients than in the general population (14.3 vs. 11.1%, P = 0.03). Additionally, the prevalence of depression was significantly higher in CKD patients with (vs. without) vitamin D deficiency (32.5% vs. 50.0%, P<0.001). Multivariate logistic regression analysis showed that vitamin D deficiency was a significant independent predictor of depression after adjusting for confounding factors (adjusted odds ratio, 6.15; 95% confidence interval, 2.02–8.75; P = 0.001). Conclusion: Depression was highly prevalent in CKD patients, in whom vitamin D deficiency was a significant independent predictor of depression. Therefore, management of vitamin D deficiency might help prevent depression in CKD patients. [ABSTRACT FROM AUTHOR]

Background: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. Methods: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. Results: During a median follow-up duration of 65 (12–154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3–0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0–2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0–2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3–0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (−0.41±1.68 vs. −0.73±2.82 ml/min/1.73 m2/year, P = 0.03). Conclusion: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3–0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to identify whether hemoglobin (Hb) concentrations can be maintained, and to investigate changes in biomarkers, when switching from erythropoietin stimulating agents (ESA) with shorter half-life to once-monthly subcutaneous methoxy polyethylene glycol-epoetin β (CERA) in pre-dialysis chronic kidney disease (CKD) patients. Methods: Pre-dialysis CKD patients (n=191) aged ≥18 years who maintained their Hb level 10-12 g/dL through use of epoetin-α, epoetin-β, or darbepoetin-α were enrolled. Hb levels and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related to coagulation, endothelial function, and iron metabolism were measured at weeks 0 and 24. Results: Baseline Hb concentration was 10.8±0.6 g/dL Twelve and 24 weeks after conversion, mean Hb levels were 11.9±0.9 and 11.2±0.9 g/dL, respectively. The mean monthly CERA dose required to maintain Hb levels was gradually reduced. Of total 387 dose adjustments, dose increases and decreases occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum soluble transferrin receptor E-selectin and prohepcidin levels were similar before and after switching to CERA (P=N-S). Conclusion: Conversion from ESA with shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients can efficaciously maintain Hb. The CERA dose requirement decreased significantly. The conversion ratio may need to be reduced when switching from ESA with shorter half-life to CERA. CERA may change biomarkers associated with platelet reactivity and endothelial microenvironment. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Despite the potential relationship with metabolic derangements, the association between dietary carbohydrate intake and renal function remains unknown. The present study investigated the impact of dietary carbohydrate intake on the development of incident chronic kidney disease (CKD) in a large-scale prospective cohort with normal renal function. A total of 6746 and 1058 subjects without and with diabetes mellitus (DM) were analyzed, respectively. Carbohydrate intake was assessed by a 24-h dietary recall food frequency questionnaire. The primary endpoint was CKD development, defined as a composite of estimated glomerular filtration rate (eGFR) of ≤60 mL/min/1.73 m2 and the development of proteinuria. CKD newly developed in 20.1% and 36.0% of subjects during median follow-ups of 140 and 119 months in the non-DM and DM subjects, respectively. Categorization of non-DM subjects into dietary carbohydrate density quartiles revealed a significantly higher risk of CKD development in the third and fourth quartiles than in the first quartile (P = 0.037 for first vs. third; P = 0.001 for first vs. fourth). A significant risk elevation was also found with increased carbohydrate density when carbohydrate density was treated as a continuous variable (P = 0.008). However, there was no significant difference in the incident CKD risk among those with DM according to dietary carbohydrate density quartiles. Carbohydrate-rich diets may increase the risk of CKD development in non-DM subjects. [ABSTRACT FROM AUTHOR]

High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1–199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02–2.87) and 2.55 (95 % CI, 1.07–6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression. [Display omitted] • Coronary artery calcification (CAC) is common in patients with chronic kidney disease (CKD). • CAC progression was more evident in patients with advanced CKD. • Greater CAC progression was associated with a higher risk for kidney failure with replacement therapy in patients with CKD. • CAC score assessment and follow-up could serve as a valuable tool for risk stratification in patients with CKD. [ABSTRACT FROM AUTHOR]

Purpose: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.Methods: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.Results: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.Conclusions: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function. [ABSTRACT FROM AUTHOR]

Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: ≥90; G 2: 60–89; G3: 30–59; G4: 15–29; G5: <15 mL/min/1.73 m2 without kidney replacement therapy). The difference in eGFR (eGFR diff) was calculated by subtracting the cystatin C-based eGFR (eGFR cys) from the creatinine-based eGFR (eGFR creat). The primary outcome was MACE, defined as non-fatal acute myocardial infarction and unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, and cardiac death. During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFR diff tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28–3.51) than the lowest tertile when adjusted for eGFR creat , eGFR cys , or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03–1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFR diff was significantly associated with accelerated CAC progression (≥50/year) (OR, 1.03; 95% CI, 1.01–1.05). A large positive difference between eGFR creat and eGFR cys was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFR diff. [Display omitted] • Cardiovascular disease is a leading cause of death in patients with chronic kidney disease. • Assessing risk of cardiovascular disease may be difficult when there is a gap between creatinine- and cystatin C-based eGFR. • Risk of major adverse cardiovascular events was high in patients with high eGFR difference between creatinine and cystatin C. • Patients with high eGFR difference also had high risk of coronary artery calcification progression. [ABSTRACT FROM AUTHOR]

Background Adiponectin is an adipokine secreted by adipocytes. A low adiponectin level is a significant risk factor of diabetes mellitus and cardiovascular disease. Recent studies have shown that adiponectin is negatively associated with hematopoiesis and predicts the development of anemia in the general population. In chronic kidney disease (CKD) patients, circulating adiponectin level is paradoxically elevated and the role of adiponectin is complex. Therefore, we evaluated the relationship between adiponectin and anemia in these patients. Methods This prospective longitudinal study included 2113 patients from the KNOW-CKD study (KoreaN cohort study for Outcome in patients With CKD), after excluding 125 without data on adiponectin levels. Hemoglobin levels were measured yearly during a mean follow-up period of 23.7 months. Anemia was defined as hemoglobin levels of <13.0 and 12.0 g/dL for men and women, respectively. Results Mean patient age was 53.6 ± 12.2 years, and 1289 (61%) were men. The mean estimated glomerular filtration rate (eGFR) was 50.4 ± 30.2 mL min −1  1.73 m −2 . Serum adiponectin level was inversely associated with body mass index, eGFR, log-transformed C-reactive protein, and positively with Charlson comorbidity index, urine protein to creatinine ratio, and high density lipoprotein cholesterol. In addition, serum adiponectin level was also negatively correlated with hemoglobin level and reticulocyte production index in both men and women. In multivariable linear regression analysis after adjustment of multiple confounders, adiponectin was negatively associated with hemoglobin (men, β  = −0.219, P  < .001; women, β  = −0.09, P  = .025). Among 1227 patients without anemia at baseline, 307 newly developed anemia during the follow-up period. In multivariable Cox regression analysis after adjustment of confounders, high adiponectin level was significantly associated with an increased risk of incident anemia (per 1 µg/mL increase, hazard ratio, 1.02; 95% confidence interval 1.01–1.04; P  = .001). Conclusions A high serum adiponectin level is independently associated with a low hemoglobin level and predicts the development of anemia in patients with CKD. These findings reveal the potential role of adiponectin in CKD-related anemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]