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.

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.

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.

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.

Changes in obese metabolic phenotypes over time and risk of incident chronic kidney disease.

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

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

BACKGROUND: Association between high body mass index (BMI) and survival benefit is confounded by comorbid conditions such as nutritional status and inflammation. Patients with acute kidney injury (AKI), particularly those receiving continuous renal replacement therapy (CRRT), are highly catabolic and more susceptible to loss of energy. Herein, we evaluated whether disease severity can modify the relationship between BMI and mortality. METHODS: We conducted an observational study in 1144 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. Patients were categorized into four groups; underweight (< 18.5 kg/m2), normal (18.5-22.99 kg/m2), overweight (23.0-24.99 kg/m2), and obesity (≥25 kg/m2) according to BMI classification by the Committee of Clinical Practice Guidelines and Korean Society for the Study of Obesity. More severe disease was defined as sepsis-related organ failure assessment (SOFA) score of ≥ a median value of 12. The study endpoint was death that occurred within 30 days after the initiation of CRRT. RESULTS: The mean age was 63.2 years and 439 (38.4%) were females. The median BMI was 23.6 (20.9-26.2) kg/m2. The obese group were younger and higher SOFA score than normal BMI group. In a multivariable Cox regression analysis, we found a significant interaction between BMI and SOFA score (P <  0.001). Furthermore, obese patients were significantly associated with a lower risk of death as compared to normal BMI group after adjusting confounding factors [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.68-0.97; P = 0.03]. This association was only evident among patients with high severity (HR, 0.61; 95% CI, 0.48-0.76, P <  0.001). In contrast, in those with low severity, survival benefit of high BMI was lost, whereas underweight was associated with an increased risk of death (HR, 1.74; 95% CI, 1.16-2.60; P = 0.007). CONCLUSION: In this study, we found a survival benefit of high BMI in AKI patients undergoing CRRT, particularly in those with more disease severity; the effect was not observed in those with less disease severity.

Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

Clinical features and outcomes of focal segmental glomerulosclerosis pathologic variants in Korean adult patients.

BACKGROUND: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. METHODS: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.

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.

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.

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

[Figure: see text].

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.

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.

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.

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.

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.

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.