Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function with chronic kidney disease.

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-ß 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.

Body weight fluctuation is associated with rapid kidney function decline.

OBJECTIVE: This study aimed to evaluate the effects of body weight fluctuations on kidney function deterioration in a prospective cohort of individuals with normal kidney function. METHODS: Data were obtained from the Korean Genome and Epidemiology Study. Body weight fluctuations were determined using average successive variability (ASV), which was defined as the average absolute body weight change using repeated measurements for all participants. The decline of the estimated glomerular filtration rate (eGFR) over time was calculated using linear regression analysis of serial eGFR measurements for each patient. Rapid eGFR decline was defined as an average eGFR decline > 3 mL/min/1.73 m2 per year. RESULTS: A total of 6,790 participants were analyzed. During a median follow-up of 11.7 years, rapid eGFR decline was observed in 913 (13.4%) participants. When the participants were categorized into tertiles according to ASV, rapid eGFR decline was more prevalent in the highest ASV tertile group than in the lowest. Analyses using multiple logistic regression models revealed that the risk of rapid eGFR decline was increased in the highest ASV tertile group compared with the lowest (odds ratio: 1.66). CONCLUSIONS: Body weight fluctuations were significantly associated with an increased risk of rapid kidney function decline in participants with normal kidney function.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD.

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.

Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition.

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD). Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories. Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06-1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06-1.87) and 2.2 (95% CI, 1.40-3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased. Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.

Association Between Longitudinal Blood Pressure Trajectory and the Progression of Chronic Kidney Disease: Results From the KNOW-CKD.

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Smoking, Smoking Cessation, and Progression of Chronic Kidney Disease: Results From KNOW-CKD Study.

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.

Dietary zinc intake and incident chronic kidney disease.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Low dietary zinc intake may increase the risk of CKD development in individuals with normal renal function.

Association of Reproductive Lifespan Duration and Chronic Kidney Disease in Postmenopausal Women.

OBJECTIVE: To investigate the relationship between endogenous estrogen exposure and renal function, the association of female reproductive life span duration (RLD) and chronic kidney disease (CKD) was analyzed in postmenopausal women. PATIENTS AND METHODS: Data were retrieved from the Korean Genome and Epidemiology Study, which was constructed from May 1, 2001, through December 25, 2017. A total of 50,338 and 3155 postmenopausal women were each included in the cross-sectional and longitudinal analyses. The RLD was determined by subtracting the age at menarche from the age at menopause. Participants were grouped into RLD quartiles. Participants with estimated glomerular filtration rates less than 60 mL/min/1.73 m2 were regarded to have CKD. RESULTS: In the cross-sectional analysis, mean ± SD age and estimated glomerular filtration rate were 56.3±4.9 years and 93.1±13.6 mL/min/1.73 m2, respectively. Mean ± SD RLD was 34.2±4.0 years. A total of 765 of 50,338 (1.52%) women were found to have CKD. Logistic regression analysis revealed that the odds ratio for CKD was lower in groups with longer RLDs as compared with the shortest RLD group. In longitudinal analysis, postmenopausal women with normal kidney function were followed up for 9.7 years and incident CKD occurred in 221 of 3155 (7.00%) participants. Cox analysis revealed that the risk for CKD development was significantly lower in longer RLD groups. This finding was significant even after adjustments for confounding factors. CONCLUSION: The risk for CKD was lower in women with longer RLDs. The amount of endogenous estrogen exposure could be a determining factor for renal function in postmenopausal women.

Nephritic Syndrome.

Nephritic syndrome is a constellation of hematuria, proteinuria, hypertension, and in some cases acute kidney injury and fluid retention characteristic of acute glomerulonephritis. Infection-related glomerulonephritis, IgA nephropathy, lupus nephritis, membranoproliferative glomerulonephritis, and antineutrophil cytoplasmic antibody-associated vasculitis are the most common diseases in nephritic syndrome that primary care physicians might encounter in practice such that a solid comprehension of these can lead to earlier detection. This article describes the pathophysiology, incidence, clinical presentation, treatment, and disease progression of these nephritic syndrome entities, and provides guidance for when to refer to a nephrologist.

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

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

Association of smoking with incident CKD risk in the general population: A community-based cohort study.

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.

Predictive value of mesangial C3 and C4d deposition in IgA nephropathy.

We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.

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

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

Alcohol Consumption and Progression of Chronic Kidney Disease: Results From the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

OBJECTIVE: To assess the association of alcohol consumption with chronic kidney disease (CKD) progression in patients with CKD. PATIENTS AND METHODS: The KoreaN cohort study for Outcome in patients with CKD (KNOW-CKD) is a prospective observational study that included detailed questionnaires regarding alcohol consumption. The 1883 individuals with CKD were enrolled from April 1, 2011, through February 28, 2016, and followed until May 31, 2017. Using a questionnaire, alcohol consumption pattern was classified according to the amount of alcohol per occasion (none, moderate, or binge) or drinking frequency (none, occasional, or regular). The primary endpoint was a composite of 50% or greater decline in estimated glomerular filtration rate (eGFR) from the baseline level or end-stage renal disease. RESULTS: During a follow-up of 5555 person-years (median, 2.95 years), the primary outcome occurred in 419 patients. Unadjusted cause-specific hazards model showed that the risk of the primary outcome was lower in drinkers than in non-drinkers. However, a fully adjusted model including eGFR and proteinuria yielded a reverse association. Compared with non-drinking, regular and occasional binge drinking were associated with a 2.2-fold (95% CI, 1.38-3.46) and a 2.0-fold (95% CI, 1.33-2.98) higher risk of CKD progression, respectively. This association was particularly evident in patients who had decreased kidney function and proteinuria. There was a significant interaction between alcohol consumption and eGFR for CKD progression. The slopes of eGFR decline were steeper in binge drinkers among patients with eGFR less than 60 mL/min/1.73 m2. CONCLUSIONS: Heavy alcohol consumption was associated with faster progression of CKD.

Snoring and incident chronic kidney disease: a community-based prospective cohort study.

OBJECTIVES: Previous studies have shown that symptoms of sleep-disordered breathing are associated with metabolic derangements and vascular disease development. However, the relationship between snoring and renal function is not well investigated. The association between snoring and the development of incident chronic kidney disease (CKD) in subjects with normal renal function was evaluated. DESIGN: Prospective cohort study. SETTING: Ansung (rural community) and Ansan (urban community) cities. PARTICIPANTS: Community-based cohort participants aged 40-69 years. METHODS: A total of 9062 participants in the Ansung-Ansan cohort study were prospectively followed up from 2001 to 2014. The participants were classified into three groups: non-snorer, <1 day/week and ≥1 day/week. The main outcome was incident CKD, which was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 during the follow-up period. PRIMARY OUTCOME: Incident CKD. RESULTS: The mean subject age was 52.0±8.9 years, and 4372 (48.2%) subjects were male. The non-snorer,<1 day/week and ≥1 day/week groups included 3493 (38.5%), 3749 (41.4%), and 1820 (20.1%) subjects, respectively. Metabolic syndrome was more prevalent in the snoring groups than in the non-snoring group. Snoring frequency showed a significant positive relationship with age, waist:hip ratio, fasting glucose, total cholesterol (Tchol) and low-density lipoprotein cholesterol. During a mean follow-up of 8.9 years, 764 (8.4%) subjects developed CKD. Cox proportional hazards model analysis revealed that the risk of CKD development was significantly higher in subjects who snored ≥1 day/week than in non-snorers, even after adjustments for confounding factors (HR 1.23, 95% CI 1.09 to 1.38, p<0.01). CONCLUSION: Snoring may increase the risk of CKD development in subjects with normal renal function.

Carbohydrate-Rich Diet Is Associated with Increased Risk of Incident Chronic Kidney Disease in Non-Diabetic Subjects.

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.

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

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

Framingham risk score and risk of incident chronic kidney disease: A community-based prospective cohort study.

BACKGROUND: Cardiovascular disease and chronic kidney disease share several common risk factors. The Framingham risk score is hypothesized to predict chronic kidney disease development. We determined if the Framingham risk scoring system can correctly predict incident chronic kidney disease in the general population. METHODS: This study included 9,080 subjects who participated in the Korean Genome and Epidemiology Study between 2001 and 2014 and had normal renal function. The subjects were classified into low- (< 10%), intermediate- (10-20%), and high- (> 20%) risk groups based on baseline Framingham risk scores. The primary endpoint was de novo chronic kidney disease development (estimated glomerular filtration rate [eGFR], < 60 mL/min/1.73 m2). RESULTS: During a mean follow-up duration of 8.9 ± 4.3 years, 312 (5.3%), 217 (10.8%), and 205 (16.9%) subjects developed chronic kidney disease in the low, intermediate, and high risk groups, respectively (P < 0.001). Multivariable analysis after adjustment for confounding factors showed the hazard ratios for the high- and intermediate risk groups were 2.674 (95% confidence interval [CI], 2.197-3.255) and 1.734 (95% CI, 1.447-2.078), respectively. This association was consistently observed irrespective of proteinuria, age, sex, obesity, or hypertension. The predictive power of this scoring system was lower than that of renal parameters, such as eGFR and proteinuria, but increased when both were included in the prediction model. CONCLUSION: The Framingham risk score predicted incident chronic kidney disease and enhanced risk stratification in conjunction with traditional renal parameters in the general population with normal renal function.

Differential effects of arterial stiffness and fluid overload on blood pressure according to renal function in patients at risk for cardiovascular disease.

The pathogenesis of hypertension is multifactorial in patients with chronic kidney disease (CKD). We explored the relative contribution of arterial stiffness and fluid overload to blood pressure (BP) in these patients. We evaluated 1531 patients from a prospective observational cohort study of high-risk patients with cardiovascular disease. BP, arterial stiffness, and volume status expressed as the extracellular water/total body water ratio (ECW/TBW) were measured by 24-h BP monitoring, pulse-wave velocity (PWV), and bioelectrical impedance analysis, respectively. Multiple linear regression analysis showed that both PWV and ECW/TBW of the patients with CKD were significantly associated with 24-h systolic BP (SBP). The areas under the receiver-operating characteristic curve (AUCs) for predicting 24-h SBP ≥130 mm Hg significantly increased after PWV was added to conventional factors regardless of CKD status. However, the AUCs did not increase in the ECW/TBW-based models. When a cut-off 24-h SBP level of 140 mm Hg was used, the predictability of ECW/TBW for elevated BP significantly improved in patients with CKD (0.718 vs. 0.683, P = 0.034) but not in those without. Notably, a significant impact of arterial stiffness on high BP was consistently observed regardless of CKD status. This association was further confirmed by the net reclassification and integrated discriminant improvements, root mean squared error with adjusted R2, and interaction effects. As kidney function declines, fluid overload is significantly associated with high BP. The impact of fluid overload on BP is only observed in more severe hypertension in patients with CKD.