Search

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. Methods: 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. Results: 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. Conclusions: This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function. [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]

The association between obesity and all-cause mortality in patients undergoing kidney failure with replacement therapy (KFRT) has shown conflicting results. This study aimed to evaluate whether metabolic abnormalities (MA) increase the risk of all-cause mortality in these patients. Between 2009 and 2015, 1141 patients undergoing KFRT were recruited from the Clinical Research Center for End-Stage Renal Disease dataset. Patients were divided into four groups according to the presence of obesity and MA. Multivariate Cox proportional hazard analysis was performed to determine the association between the phenotypes and all-cause mortality. During a mean follow-up of 4.2 years, all-cause mortality was observed in 491 (43.0%) patients. Obesity had a 24% decreased risk of all-cause mortality compared with non-obesity. In contrast, the presence of MA showed a 1.53-fold increased risk of all-cause mortality. There was a significant interaction between obesity and MA (p = 0.006). In Cox proportional hazard analyses after adjustment of confounding factors, the metabolically abnormal non-obesity (MANO) phenotype showed a 1.63-fold increased risk of all-cause mortality compared with the metabolically healthy non-obesity phenotype. In subgroup analysis, the risk of all-cause mortality was higher in the MANO phenotype; this phenotype was significantly associated with a higher all-cause mortality in patients undergoing KFRT. [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]

Kidney fibrosis is a common pathophysiological mechanism of chronic kidney disease (CKD) progression caused by several underlying kidney diseases. Among various contributors to kidney fibrosis, transforming growth factor-β1 (TGF-β1) is the major factor driving fibrosis. TGF-β1 exerts its profibrotic attributes via the activation of canonical and non-canonical signaling pathways, which induce proliferation and activation of myofibroblasts and subsequent accumulation of extracellular matrix. Over the past few decades, studies have determined the TGF-β1 signaling pathway inhibitors and evaluated whether they could ameliorate the progression of CKD by hindering kidney fibrosis. However, therapeutic strategies that block TGF-β1 signaling have usually demonstrated unsatisfactory results. Herein, we discuss the therapeutic concepts of the TGF-β1 signaling pathway and its inhibitors and review the current state of the art regarding regarding TGF-β1 inhibitors in CKD management. [ABSTRACT FROM AUTHOR]

Objectives Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout. Methods We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3–G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex. Results Overall, 3085 patients with CKD progression were matched to 11   715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3. Conclusion Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout. [ABSTRACT FROM AUTHOR]

Background Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. Methods Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: <110, 110–119, 120–129, 130–139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs. Results During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7–26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110–119 mmHg, hazard ratios (95% CI) for <110, 120–129, 130–139 and ≥140 mmHg were 2.47 (1.48–4.11), 1.29 (0.80–2.08), 2.15 (1.26–3.69) and 2.19 (1.19–4.01), respectively. MSMs with the most recent SBP also showed similar findings. Conclusions In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg. [ABSTRACT FROM AUTHOR]

Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42–0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, − 3.7; 95% CI − 5.7 to − 1.7; P < 0.001). Incidence rate ratio (IRR) was also consistent with other analyses (IRR, 0.56; 95% CI, 0.41 to 0.78; P < 0.001). Statin use was associated with a lower risk of incident HCC in dialysis patients with chronic hepatitis B or C infection. [ABSTRACT FROM AUTHOR]

Objective: Increasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management. Yet, little is known regarding cardiovascular risks associated with the length of favourable cardiometabolic profile. In this context, we examined whether the duration of strictly ideal cardiovascular health (CVH), based on body mass index, blood pressure, fasting glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD) in mid-to-late life.Methods: From the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Cox proportional hazards models were employed to assess CKD and CVD risks, adjusting for age, sex, education level, examination sites and renal markers.Results: Over a median follow-up of 15.0 years, 1401 cases of CKD and 493 cases of CVD were newly developed. Compared with participants with <5 years of ideal CVH duration, HR (95% CI) of those who maintained for 5-<10 years or ≥10 years had negatively graded risks for CKD (5-<10 years, 0.63 (0.39 to 0.93); ≥10 years, 0.33 (0.15 to 0.74)) and CVD (5-<10 years, 0.83 (0.54 to 1.27); ≥10 years, 0.22 (0.08 to 0.60)). In parallel, participants with delayed decline to suboptimal level had lower disease risks compared with counterparts with consistently suboptimal CVH.Conclusion: Our findings confer that maintaining favourable health behaviours and clinical risk factor levels in midlife will improve later-life cardiovascular outcomes. [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 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]

Background Urinary chloride is regulated by kidney transport channels, and high urinary chloride concentration in the distal tubules can trigger tubuloglomerular feedback. However, little attention has been paid to urinary chloride as a biomarker of clinical outcomes. Here, we studied the relationship between urinary chloride concentration and chronic kidney disease (CKD) progression. Methods We included 2086 participants with CKD from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease. Patients were categorized into three groups, according to baseline urinary chloride concentration tertiles. The study endpoint was a composite of ≥50% decrease in estimated glomerular filtration rate from baseline values, or end-stage kidney disease. Results During a median follow-up period of 3.4 years (7452 person-years), 565 participants reached the primary endpoint. There was a higher rate of CKD progression events in the lowest and middle tertiles than in the highest tertile. Compared with the lowest tertile, the highest tertile was associated with 33% [95% confidence interval (CI) 0.49–0.90] lower risk for the primary outcome in a cause-specific hazard model after adjustment for confounding variables. In addition, for every 25 mEq/L increase in urinary chloride concentration, there was 11% (95% CI 0.83–0.96) lower risk for CKD progression. This association was consistent in a time-varying model. Urinary chloride concentration correlated well with tubule function and kidney injury markers, and its predictive performance for CKD progression was comparable to that of these markers. Conclusions In this hypothesis-generating study, low urinary chloride concentration was associated with a higher risk for CKD progression. [ABSTRACT FROM AUTHOR]

Few studies have investigated the incidence of cardiovascular disease (CVD) in the Asian chronic kidney disease (CKD) population. This study assessed the incidence of CVD, death, and a composite outcome of CVD and death in a prospective Korean predialysis CKD cohort. From a total of 2179 patients, incidence rates were analyzed, and competing risk analyses were conducted according to CKD stage. Additionally, incidence was compared to the general population. During a median 4.1 years of follow-up, the incidence of CVD, all-cause death, and the composite outcome was 17.2, 9.6, and 24.5 per 1000 person-years, respectively. These values were higher in diabetic vs. non-diabetic subjects (P < 0.001). For all outcomes, incidence rates increased with increasing CKD stage (CVD, P = 0.001; death, P < 0.001; and composite, P < 0.001). Additionally, CKD stage G4 [hazard ratio (HR) 2.8, P = 0.008] and G5 (HR 5.0, P < 0.001) were significant risk factors for the composite outcome compared to stage G1 after adjustment. Compared to the general population, the total cohort population (stages G1–G5) showed significantly higher risk of CVD (HR 2.4, P < 0.001) and the composite outcome (HR 1.7, P < 0.001). The results clearly demonstrate that CKD is a risk factor for CVD in an Asian population. [ABSTRACT FROM AUTHOR]

Introduction: In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce.Aims and Methods: We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation.Results: There were 967 never-smokers and 369, 276, and 339 smokers who smoked <15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4-63.5), 46.9 (35.9-61.4), 69.2 (52.9-90.6), and 76.3 (60.7-96.0) events per 1,000 person-yr in never-, <15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73-1.63), 1.48 (1.00-2.18), and 1.94 (1.35-2.77) fold increased risk (95% CI) of primary outcome in <15, 15-29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR < 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers.Conclusions: These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD.Implications: Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a public health problem, and an unfavorable lifestyle has been suggested as a modifiable risk factor for CKD. Cigarette smoking is closely associated with cardiovascular disease and cancers; however, there is a lack of evidence to prove that smoking is harmful for kidney health. Therefore, we aimed to determine the relationship between cigarette smoking and CKD among healthy middle-aged adults. Methods: Using the database from the Korean Genome and Epidemiology Study, we analyzed 8,661 participants after excluding those with baseline estimated glomerular filtration rate (eGFR)<60 ml/min/1.72 m2 or proteinuria. Exposure of interest was smoking status: never-, former-, and current-smokers. Primary outcome was incident CKD defined as eGFR <60 ml/min/1.73 m2 or newly developed proteinuria. Results: The mean age of the subjects was 52 years, and 47.6% of them were males. There were 551 (6.4%) and 1,255 (14.5%) subjects with diabetes and hypertension, respectively. The mean eGFR was 93.0 ml/min/1.73 m2. Among the participants, 5,140 (59.3%), 1,336 (15.4%), and 2,185 (25.2%) were never-smokers, former-smokers, and current-smokers, respectively. During a median follow-up of 11.6 years, incident CKD developed in 1,941 (22.4%) subjects with a crude incidence rate of 25.1 (24.0–26.2) per 1,000 person-years. The multivariable Cox regression analysis after adjustment of confounding factors showed hazard ratios (95% confidence interval) of 1.13 (0.95–1.35) and 1.26 (1.07–1.48) for CKD development in the former- and current-smokers, compared with never-smokers. Conclusion: This study showed that smoking was associated with a higher risk of incident CKD among healthy middle-aged adults. [ABSTRACT FROM AUTHOR]

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

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]

Summary: Abnormal bone dynamics is a major risk factor for cardiovascular disease in patients with chronic kidney disease. The level of serum intact parathyroid hormone (iPTH) is widely used as a bone dynamic marker. We investigated the effect of the mean level of serum iPTH on overall mortality and cardiovascular outcomes in incident dialysis patients. Purpose: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major risk factor for cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). CKD-MBD is classified as low- or high-turnover bone disease according to the bone dynamics; both are related to vascular calcification in ESRD. To evaluate the prognostic value of abnormal serum parathyroid hormone (PTH) levels on ESRD patients, we investigated the effects of time-averaged serum intact PTH (TA-iPTH) levels on overall mortality and major adverse cardiac and cerebrovascular events (MACCEs) in incident dialysis patients. Methods: Four hundred thirteen patients who started dialysis between January 2009 and September 2013 at Yonsei University Health System were enrolled. The patients were divided into three groups according to TA-iPTH levels during the 12 months after the initiation of dialysis: group 1, <65 pg/ml; group 2, 65-300 pg/ml; and group 3, >300 pg/ml. Cox regression analyses were performed to determine the prognostic value of TA-iPTH for overall mortality and MACCEs. Results: The mean age of the patients was 57 ± 15 years, and 222 patients (54 %) were men. During the median follow-up of 40.8 ± 29.3 months, 49 patients (12 %) died, and MACCEs occurred in 55 patients (13 %). The multivariate Cox regression analyses demonstrated that a low TA-iPTH level was an independent risk factor for both overall mortality (group 2 as reference; group 1: hazard ratio (HR) = 2.06, 95 % confidence interval (CI) = 1.11-3.83, P = 0.023) and MACCEs (HR = 1.82, 95 % CI = 1.04-3.20, P = 0.036) in incident dialysis patients after adjustment for confounding factors. Conclusion: Low serum TA-iPTH is a useful clinical marker of both overall mortality and MACCEs in patients undergoing incident dialysis, mediated by vascular calcification. [ABSTRACT FROM AUTHOR]

Background: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. Methods: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. Results: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). Conclusion: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Diastolic heart failure (HF), the prevalence of which is gradually increasing, is associated with cardiovascular (CV) morbidity and mortality in the general population and, more specifically, in patients with end-stage renal disease (ESRD). However, the impact of diastolic dysfunction on CV outcomes has not been studied in incident dialysis patients with preserved systolic function. Methods: This prospective observational cohort study investigates the clinical consequence of diastolic dysfunction and the predictive power of diastolic echocardiographic parameters for CV events in 194 incident ESRD patients with normal or near normal systolic function, who started dialysis between July 2008 and August 2012. Results: During a mean follow-up duration of 27.2 months, 57 patients (29.4%) experienced CV events. Compared to the CV event-free group, patients with CV events had a significantly higher left ventricular (LV) mass index, ratio of early mitral flow velocity (E) to early mitral annulus velocity (E’) (E/E’), LA volume index (LAVI), deceleration time, and right ventricular systolic pressure, and a significantly lower LV ejection fraction and E’. In multivariate Cox proportional hazard analysis, E/E’>15 and LAVI>32 mL/m2 significantly predicted CV events (E/E’>15: hazard ratio [HR] = 5.40, 95% confidence interval [CI] = 2.73–10.70, P< .001; LAVI>32 mL/m2: HR = 5.56, 95% CI = 2.28–13.59, P< .001]. Kaplan-Meier analysis revealed that patients with both E/E’>15 and LAVI>32mL/m2 had the worst CV outcomes. Conclusion: An increase in E/E’ or LAVI is a significant risk factor for CV events in incident dialysis patients with preserved LV systolic function. [ABSTRACT FROM AUTHOR]

Background and Aim: Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients. Methods: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients. Results: Among the baseline parameters, serum sodium level was positively associated with serum albumin (β = 0.145; p = 0.003) and residual renal function (RRF) (β = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (β = −0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73–0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70–0.85; p<0.001) deaths. Conclusions: This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately. [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]

Backgrounds and Aims: Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients. Methods: We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients. Results: The mean SAD was 24.5±4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514–7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005–1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994–32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007–1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m2). Conclusions: SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients. [ABSTRACT FROM AUTHOR]

Objective. Percutaneous transluminal renal artery angioplasty and stenting (PTRAS) is one treatment option for atherosclerotic renal artery stenosis (ARAS). However, factors predicting the outcome remain controversial. This study investigated the effect of the baseline glomerular filtration rate (GFR) on renal function after PTRAS in patients with ARAS. Material and methods. Patients who underwent PTRAS due to significant ARAS (luminal narrowing ≥ 60%) were enrolled. The patients were divided into control ( n = 57; estimated GFR (eGFR) ≥ 60 ml/min/1.73 m2) and chronic renal failure (CRF) groups ( n = 53; eGFR < 60 ml/min/1.73 m2), according to the baseline eGFR. Results. The mean age at the time of PTRAS was 62 ± 9 years, and the mean duration of follow-up was 50 ± 26 months. There was a significant decrease in eGFR after PTRAS in the control group, whereas the CRF group showed no significant change in eGFR. The percentage change in eGFR was negatively correlated with the baseline eGFR ( r = –0.274, p = 0.004). Multivariate linear regression revealed that only baseline eGFR predicted the change in eGFR ( p = 0.032). Conclusions. PTRAS was more effective at preserving renal function in patients with moderately impaired renal function. Thus, baseline GFR may indicate the expected renal function outcome after PTRAS. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-β) is well known for epithelial–mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-β superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-β, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signaling in vivo. Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-β–mediated epithelial–mesenchymal transition process in vitro and in an in vivo unilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman's space and inhibits unilateral ureter obstruction–induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-β–mediated renal fibrosis and other organs as well as a clinically available approach for kidney. [ABSTRACT FROM AUTHOR]

End-stage renal disease (ESRD) is the final stage of chronic kidney disease, which is increasingly prevalent worldwide and is associated with the progression of cardiovascular disease (CVD). Indoxyl sulfate (IS), a major uremic toxin, plays a key role in the pathology of CVD via adverse effects in endothelial and immune cells. Thus, there is a need for a transcriptomic overview of IS responsive genes in immune cells of ESRD patients. Here, we investigated IS-mediated alterations in gene expression in monocytes from ESRD patients. Transcriptomic analysis of ESRD patient-derived monocytes and IS-stimulated monocytes from healthy controls was performed, followed by analysis of differentially expressed genes (DEGs) and gene ontology (GO). We found that 148 upregulated and 139 downregulated genes were shared between ESRD patient-derived and IS-stimulated monocytes. Interaction network analysis using STRING and ClueGo suggests that mainly metabolic pathways, such as the pentose phosphate pathway, are modified by IS in ESRD patient-derived monocytes. These findings were confirmed in IS-stimulated monocytes by the increased mRNA expression of genes including G6PD, PGD, and TALDO1. Our data suggest that IS causes alteration of metabolic pathways in monocytes of ESRD patients and, thus, these altered genes may be therapeutic targets. [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]

Following publication of the original article [1], an error in one of the author names was reported. In this Correction the incorrect and correct author names are listed. [ABSTRACT FROM AUTHOR]

Background: Left 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. Methods: Data 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. Results: A 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). Conclusions: In 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. [ABSTRACT FROM AUTHOR]

Background: Klotho, a protein linked to aging, has emerged as a pivotal player in mineral bone metabolism and might explain the relationship between chronic kidney disease (CKD) and cardiovascular disease (CVD). The present study aimed to investigate the association between serum klotho and cardiac parameters from a large-scale Korean CKD cohort.Methods: We analyzed 2101 participants from KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort who had been measured for serum klotho levels. Left ventricular hypertrophy evaluated by left ventricular mass index (LVMI) and arterial stiffness measured by brachial-to-ankle pulse wave velocity (baPWV) were explored as cardiovascular parameters.Results: Patients were 53.6 ± 12.2 years old and 61.1% were male. The mean estimated glomerular filtration rate (eGFR) was 53.0 ± 30.7 mL/min/1.73m2. The median serum klotho level was 536 (interquartile range [IQR]: 420-667) pg/mL. Advanced CKD stages were associated with lower serum klotho levels (P < 0.001, P for linear trend < 0.001). Ascending quartiles of klotho were significantly associated with decreased LMVI (P < 0.001, P for linear trend< 0.001). A multivariable linear regression model showed serum klotho had a significant inverse association with LVMI (β - 0.04; 95% CI [confidence interval] -0.004, - 0.00007; P = 0.041). However, there was no significant association between serum klotho and baPWV after adjustment (β 0.003; 95% CI -0.04, 0.05; P = 0.876).Trial Registration: This trial was registered on ClinicalTrials.gov on 28 June 2012 ( NCT01630486 ).Conclusions: Serum klotho was an independent biomarker of LVMI, but not arterial stiffness. [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]

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]

Abstract: Aims: We sought not only to determine the independent predictors of non-diabetic renal disease (NDRD) but also to investigate the impact of NDRD on renal outcomes in patients with type 2 diabetes who underwent renal biopsy and were followed-up longitudinally. Methods: The present study was conducted by reviewing the medical records of 119 type 2 diabetic patients who underwent renal biopsy at Yonsei University Health System from January 1988 to December 2008. Results: Renal biopsy findings declared that 43 patients (36.1%) had diabetic nephropathy alone, 12 (10.1%) had NDRD superimposed on diabetic nephropathy, and 64 (53.8%) had only NDRD. On multivariate analysis, the absence of diabetic retinopathy, higher hemoglobin levels, and shorter duration of diabetes were independent predictors of NDRD in these patients. During the follow-up period, end-stage renal disease (ESRD) developed in 33 patients (27.7%). On multivariate Cox regression, higher serum creatinine levels, higher systolic blood pressure, longer duration of diabetes, and the presence of diabetic nephropathy were identified as significant independent predictors of ESRD. When the presence of diabetic retinopathy was included in the multivariate model, higher serum creatinine levels, higher systolic blood pressure, and the presence of retinopathy were shown to be independent predictors of ESRD. Conclusions: Since diabetic patients with NDRD have significantly better renal outcomes compared to patients with biopsy-proven diabetic nephropathy, it is important to suspect, identify, and manage NDRD as early as possible, especially in type 2 diabetic patients with short duration of diabetes and those without diabetic retinopathy or anemia. [Copyright &y& Elsevier]

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]