Metabolically Abnormal Non-Obese Phenotype Is Significantly Associated with All-Cause Mortality in Hemodialysis Patients.

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.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

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.

Presence of periodontal disease and the incidence of inflammatory arthritides in the general population: data from the UK Biobank.

OBJECTIVES: To investigate the association between periodontal disease and the development of inflammatory arthritides (IA) in the general population. METHODS: In total, 489 125 participants from the UK Biobank without a previous history of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) were enrolled. The primary outcome was the incidence of IA, which was a composite of RA, AS, and PsA according to the presence of periodontal disease based on self-reported oral health indicators. Multivariate Cox proportional hazard regression analyses using four different models were performed to assess the association between periodontal disease and IA development. RESULTS: In all, 86 905 and 402 220 individuals were categorized as with and without periodontal disease, respectively. Cox hazard analysis indicated that the presence of periodontal disease was an independent predictor of the occurrence of composite outcomes of IA, which was also consistent for RA and AS. Significant associations were found to be consistent in the four Cox models and were replicated even when different criteria were used to define periodontal disease. Subgroup analyses indicated that periodontal disease was associated with an increased RA risk in those aged <60 years, and this risk was persistent for both male and female patients and for patients with seropositive/seronegative RA. CONCLUSION: Self-reported periodontal disease is associated with IA incidence in participants included in the UK Biobank, particularly for RA and AS. Higher clinical attention and optimal dental care in patients with signs of periodontal disease may be recommended for early disease detection and for reducing this risk.

Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease.

BACKGROUND: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). METHODS: This study included 2,149 patients with CKD G1-G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922-0.960) and eGFRcr (0.941; 95% CI, 0.922-0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). CONCLUSION: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.

Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.

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.

Association of short-term and long-term weight loss with the risk of major adverse cardiovascular disease: Community-based cohort study.

BACKGROUND: This study evaluated temporal association of changes in BMI over time with major adverse cardiovascular event (MACE) in Korean middle-aged adults. METHODS: Between 2001 and 2002, 6855 individuals from the Korean Genome and Epidemiology Study were included and followed up until 2014. The main predictor was the change in BMI determined using group-based trajectory modelling (decreasing, stable, and increasing) from the baseline to 4-, 6-, and 8-years of follow-up. The primary outcome was the occurrence of MACE. RESULTS: During the mean 10.2 years follow-up, MACEs occurred in 350 (5.1 %) individuals. The median (interquartile rage) age of study population was 50 (44-59) years. In primary analysis with 4-year trajectory model, decreasing BMI trajectory was associated with a 1.41-fold higher risk of the MACEs (hazard ratio [HR], 1.41; 95 % confidence interval [CI], 1.06-1.91) compared with stable BMI trajectory. In secondary analyses with 6- and 8-year trajectory models, this association disappeared, and the corresponding HRs (95 % CIs) were 1.14 (0.81-1.61) and 0.98 (0.65-1.49), respectively. There were concomitant improvements in cardiometabolic risk factors in decreasing BMI group, but unfavorable risk burden remained up to 4 to 6 years. CONCLUSIONS: The initial 4-year weight loss was paradoxically associated with a higher risk of MACEs, probably due to residual cardiovascular burden. However, this association became null in participants with sustained weight loss ≥ 6 years, suggesting a possible lag effect of weight loss on MACEs.

Machine Learning Improves the Prediction Rate of Non-Curative Resection of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer.

Non-curative resection (NCR) of early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) can increase the burden of additional treatment and medical expenses. We aimed to develop a machine-learning (ML)-based NCR prediction model for EGC prior to ESD. We obtained data from 4927 patients with EGC who underwent ESD between January 2006 and February 2020. Ten clinicopathological characteristics were selected using extreme gradient boosting (XGBoost) and were used to develop a ML-based model. Dataset was divided into the training and internal validation sets and verified using an external validation set. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were evaluated. The performance of each model was compared by using the Delong test. A total of 1100 (22.1%) patients were identified as being treated non-curatively with ESD. Seven ML-based NCR prediction models were developed. The performance of NCR prediction was highest in the XGBoost model (AUROC, 0.851; 95% confidence interval, 0.837-0.864). When we compared the prediction performance by the Delong test, XGBoost (p = 0.02) and support vector machine (p = 0.02) models showed a significantly higher performance among the NCR prediction models. We developed an ML model capable of accurately predicting the NCR of EGC before ESD. This ML model can provide useful information for decision-making regarding the appropriate treatment of EGC before ESD.

Coronary Artery Calcification Score and the Progression of Chronic Kidney Disease.

BACKGROUND: An elevated coronary artery calcification score (CACS) is associated with increased cardiovascular disease risk in patients with CKD. However, the relationship between CACS and CKD progression has not been elucidated. METHODS: We studied 1936 participants with CKD (stages G1-G5 without kidney replacement therapy) enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD. The main predictor was Agatston CACS categories at baseline (0 AU, 1-100 AU, and >100 AU). The primary outcome was CKD progression, defined as a ≥50% decline in eGFR or the onset of kidney failure with replacement therapy. RESULTS: During 8130 person-years of follow-up, the primary outcome occurred in 584 (30.2%) patients. In the adjusted cause-specific hazard model, CACS of 1-100 AU (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.04 to 1.61) and CACS >100 AU (HR, 1.42; 95% CI, 1.10 to 1.82) were associated with a significantly higher risk of the primary outcome. The HR associated with per 1-SD log of CACS was 1.13 (95% CI, 1.03 to 1.24). When nonfatal cardiovascular events were treated as a time-varying covariate, CACS of 1-100 AU (HR, 1.31; 95% CI, 1.07 to 1.60) and CACS >100 AU (HR, 1.46; 95% CI, 1.16 to 1.85) were also associated with a higher risk of CKD progression. The association was stronger in older patients, in those with type 2 diabetes, and in those not using antiplatelet drugs. Furthermore, patients with higher CACS had a significantly larger eGFR decline rate. CONCLUSION: Our findings suggest that a high CACS is associated with significantly increased risk of adverse kidney outcomes and CKD progression.

Colchicine use and the risk of CKD progression: a multicentre nested case-control study.

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.

Association of blood pressure with cardiovascular outcome and mortality: results from the KNOW-CKD study.

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.

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.

Erythropoiesis stimulating agent recommendation model using recurrent neural networks for patient with kidney failure with replacement therapy.

In patients with kidney failure with replacement therapy (KFRT), optimizing anemia management in these patients is a challenging problem because of the complexities of the underlying diseases and heterogeneous responses to erythropoiesis-stimulating agents (ESAs). Therefore, we propose a ESA dose recommendation model based on sequential awareness neural networks. Data from 466 KFRT patients (12,907 dialysis sessions) in seven tertiary-care general hospitals were included in the experiment. First, a Hb prediction model was developed to simulate longitudinal heterogeneous ESA and Hb interactions. Based on the prediction model as a prospective study simulator, we built an ESA dose recommendation model to predict the required amount of ESA dose to reach a target hemoglobin level after 30 days. Each model's performance was evaluated in the mean absolute error (MAE). The MAEs presenting the best results of the prediction and recommendation model were 0.59 (95% confidence interval: 0.56-0.62) g/dL and 43.2 µg (ESAs dose), respectively. Compared to the results in the real-world clinical data, the recommendation model achieved a reduction of ESA dose (Algorithm: 140 vs. Human: 150 µg/month, P < 0.001), a more stable monthly Hb difference (Algorithm: 0.6 vs. Human: 0.8 g/dL, P < 0.001), and an improved target Hb success rate (Algorithm: 79.5% vs. Human: 62.9% for previous month's Hb < 10.0 g/dL; Algorithm: 95.7% vs. Human:73.0% for previous month's Hb 10.0-12.0 g/dL). We developed an ESA dose recommendation model for optimizing anemia management in patients with KFRT and showed its potential effectiveness in a simulated prospective study.

Endoscopic Vacuum Therapy in Patients with Transmural Defects of the Upper Gastrointestinal Tract: A Systematic Review with Meta-Analysis.

A transmural defect of the upper gastrointestinal (UGI) tract is a life-threatening condition associated with high morbidity and mortality. Recently, endoscopic vacuum therapy (EVT) was used for managing UGI defects and showed promising results. We conducted a systematic review and meta-analysis to synthesize evidence on the efficacy of EVT in patients with transmural defects of the UGI tract. We searched the PubMed, Cochrane Library, and Embase databases for publications on the effect of EVT on successful closure, mortality, complications, and post-EVT strictures. Methodological quality was assessed using the Newcastle-Ottawa quality assessment scale. This meta-analysis included 29 studies involving 498 participants. The pooled estimate rate of successful closure with EVT was 0.85 (95% confidence interval [CI]: 0.81-0.88). The pooled estimate rates for mortality, complications, and post-EVT strictures were 0.11, 0.10, and 0.14, respectively. According to the etiology of the transmural defect (perforation vs. leak and fistula), no significant difference was observed in successful closure (odds ratio [OR]: 1.45, 95% CI: 0.45-4.67, p = 0.53), mortality (OR: 0.77, 95% CI: 0.24-2.46, p = 0.66), complications (OR: 0.94, 95% CI: 0.17-5.15, p = 0.94), or post-EVT stricture rates (OR: 0.70, 95% CI: 0.12-4.24, p = 0.70). The successful closure rate was significantly higher with EVT than with self-expanding metal stent (SEMS) placement (OR: 3.14, 95% CI: 1.23-7.98, p = 0.02). EVT is an effective and safe treatment for leaks and fistulae, as well as for perforations in the UGI. Moreover, EVT seems to be a better treatment option than SEMS placement for UGI defects.

Association of Blood Pressure With the Progression of CKD: Findings From KNOW-CKD Study.

RATIONALE & OBJECTIVE: Optimal blood pressure (BP) control is a major therapeutic strategy in the management of chronic kidney disease (CKD). We studied the association between BP and adverse kidney outcomes within a diverse cohort of Koreans with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 2,044 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). EXPOSURES: Baseline and time-updated systolic BP (SBP) and diastolic BP (DBP). OUTCOME: A composite kidney outcome of a≥50% decline in estimated glomerular filtration rate (eGFR) from the baseline value or incident kidney replacement therapy. ANALYTICAL APPROACH: Multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BP, respectively. RESULTS: During 7,472 person-years of follow-up, the primary composite kidney outcome occurred in 473 participants (23.1%), an incidence rate of 63.3 per 1,000 patient-years. Compared with baseline SBP<120mm Hg, the hazard ratios (HRs) for 120-129, 130-139, and≥140mm Hg were 1.10 (95% CI, 0.83-1.44), 1.20 (95% CI, 0.93-1.59), and 1.43 (95% CI, 1.07-1.91), respectively. This association was more evident in the model with time-updated SBP, for which the corresponding HRs were 1.31 (95% CI, 0.98-1.75), 1.59 (95% CI, 1.16-2.16), and 2.29 (95% CI, 1.69-3.11), respectively. In the analyses of DBP, we observed that time-updated DBP but not baseline DBP was significantly associated with the composite kidney outcome. Compared to patients with SBP<120mm Hg, patients with higher SBP had steeper slopes of eGFR decline. In the model including both SBP and DBP, only SBP was significantly associated with the composite kidney outcome. LIMITATIONS: Observational design, unmeasured confounders, and use of office BPs only. CONCLUSIONS: In patients with CKD, higher SBP and DBP levels were associated with a higher risk of a composite kidney outcome reflecting CKD progression. SBP had a greater association with adverse kidney outcomes than DBP.

Urinary chloride concentration and progression of chronic kidney disease: results from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease.

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.

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.

Association of Longitudinal Trajectories of Systolic BP with Risk of Incident CKD: Results from the Korean Genome and Epidemiology Study.

BACKGROUND: Although hypertension is a well known risk factor for CKD, few studies have evaluated the association between temporal trends of systolic BP and kidney function decline in persons without hypertension. METHODS: We studied whether changes in systolic BP over time could influence incident CKD development in 4643 individuals without CKD and hypertension participating in the Korean Genome and Epidemiology Study, a prospective community-based cohort study. Using group-based trajectory modeling, we categorized three distinct systolic BP trajectories: decreasing, stable, and increasing. The primary outcome was incident CKD development, defined as two consecutive eGFR measurements <60 ml/min per 1.73 m2. RESULTS: Among participants with an increasing systolic BP trajectory, systolic BP increased from 105 to 124 mm Hg. During 31,936 person-years of follow-up (median 7.7 years), 339 participants developed incident CKD. CKD incidence rates were 8.9, 9.6, and 17.8 cases per 1000 person-years in participants with decreasing, stable, and increasing systolic BP trajectories, respectively. In multivariable cause-specific Cox analysis, after adjustment of baseline eGFR, systolic BP, and other confounders, increasing systolic BP trajectory associated with a 1.57-fold higher risk of incident CKD (95% confidence interval, 1.20 to 2.06) compared with a stable trajectory. There was a significant effect modification of baseline systolic BP on the association between systolic BP trajectories and CKD risk (P value for interaction =0.02), and this association was particularly evident in participants with baseline systolic BP <120 mm Hg. In addition, increasing systolic BP trajectory versus a stable trajectory was associated with higher risk of new development of albuminuria. CONCLUSIONS: Increasing systolic BP over time without reaching the hypertension threshold is associated with a significantly increased risk of incident CKD in healthy adults.