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Objectives To investigate the association between periodontal disease and the development of inflammatory arthritides in the general population. Methods In total, 489 125 participants from the UK Biobank without a previous history of RA, AS and PsA were enrolled. The primary outcome was the incidence of inflammatory arthritides, 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 inflammatory arthritides 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 inflammatory arthritides, 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 inflammatory arthritides 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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

Simple Summary: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment for early gastric cancer (EGC). Non-curative resection (NCR) of EGC after ESD can increase the burden of additional treatment and medical expenses. Thus, 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. Seven ML-based NCR prediction models were developed using ten clinicopathological characteristics. The performance of NCR prediction was highest in the XGBoost model (AUROC, 0.851; 95% confidence interval, 0.837–0.864). Our ML model improved the ability to predict NCR of ESD in patients with EGC. This ML model can provide useful information for decision-making regarding the appropriate treatment of EGC before ESD. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

Background:The Oxford classification has been widely used in IgA nephropathy. However, its clinical usefulness of determining immunosuppression is unknown. Aim:Whether the Oxford classification could predict the development of proteinuria ≥1 g/g Cr and worsening kidney function, as well as the clinical efficacy of corticosteroid treatment according to each histologic variable of the Oxford-MEST. Methods:We included 377 patients with early-stage IgA nephropathy. The study endpoints were the development of a heavy proteinuria and a decline renal function. Results:The results showed that among the Oxford-MEST lesions, only M1 predicted the risk of the development of proteinuria ≥1.0 g/g Cr compared to other lesions in a time-varying Cox model adjusted for multiple confounding factors. In addition, the risk of reaching a 30% decline in eGFR was significantly higher in patients with M1 than in those with M0. Furthermore, patients with M1 had a greater decline of eGFR than patients with M0. However, steroid treatment in M1 lesion was not associated with improving clinical outcomes in the unmatched and propensity score matched cohort. Conclusions:This finding may provide a rationale for using the Oxford classification as a guidance to initiate immunosuppression in the early stages of IgA nephropathy.KEY MESSAGESM1 has independently predictive role among the Oxford lesions in IgA nephropathy.Oxford classification should be defined during pathologic approach.Decision of starting immunosuppression according to the Oxford lesions. [ABSTRACT FROM PUBLISHER]

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

ABSTRACT Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log-transformed plasma DMP1 levels. Lateral lumbar spine radiographs were used for measurement of vascular calcification. Major cardiovascular events were compared between the two groups. A Cox proportional hazards analysis determined DMP1 was independently associated with cardiovascular outcomes. In vitro mouse osteocytes were cultured in media containing indoxyl sulfate (IS), and the expressions of DMP1 were examined. The mean age was 52.1 ± 11.8 years, and 116 (52.0%) patients were male. The median value of log DMP1 was 0.91 (0.32-2.81 ng/mL). The multiple logistic regression analysis indicated that DMP1 levels were independently associated with the presence of vascular calcification after adjustment for multiple confounding factors (odds ratio = 0.719; 95% confidence interval [CI] 0.522-0.989; p = 0.043). During a mean follow-up duration of 34.6 months, incident cardiovascular events were observed in 41 (18.4%) patients. A Kaplan-Meier plot showed that the low DMP1 group had a significantly higher rate of incident cardiovascular events compared with the high DMP1 group (log-rank test, p = 0.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio = 0.855; 95% CI 0.743-0.984; p = 0.029) after adjustment for multiple confounding factors. In IS-stimulated osteocytes, mRNA and protein expression levels of DMP1 were significantly decreased compared with control osteocytes. We showed that low DMP1 levels were significantly associated with presence of vascular calcification and were independently associated with the incident cardiovascular events in prevalent peritoneal dialysis patients. DMP1 might be a potential factor contributing to cardiovascular complications in dialysis patients. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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 &lt;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.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yun, Kim, Chang, Kang, Joo, Nam, Kim, Park, Yoo, Kang and Han.)

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., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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 m 2 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 m 2 , 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., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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 m 2 ., 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., (Copyright © 2020 by the American Society of Nephrology.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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 m 2 ., Conclusions: Heavy alcohol consumption was associated with faster progression of CKD., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Aldosterone-induced glomerular hyperfiltration can lead to masked preoperative renal dysfunction in primary aldosteronism(PA) patients. We evaluated whether PA patients had a higher prevalence of acute kidney injury (AKI) after unilateral adrenalectomy. In addition, we identified risk factors for AKI in these subjects., Methods: This retrospective study included 107 PA patients, and 186 pheochromocytoma patients as a control group, all of whom underwent adrenalectomy between January 2006 and November 2017 at Yonsei University Severance Hospital. The primary outcome was AKI within 48 hours after adrenalectomy. Univariate and multivariate logistic regression analyses were performed to identify predictors of AKI after adrenalectomy., Results: Overall incidence of AKI was 49/293 (16.7%). In PA patients, the incidence of AKI was 29/107 (27.1%). In contrast, incidence of AKI was 20/186 (10.7%) in pheochromocytoma patients. Univariate and multivariate logistic regression analysis both showed a higher risk of postoperative AKI in PA patients compared to pheochromocytoma patients. In addition, old age, diabetes, longer duration of hypertension, lower preoperative estimated glomerular filtration rate, high aldosterone-cortisol ratio (ACR) and lateralization index (LI) were identified as independent risk factors for postoperative AKI in PA patients after unilateral adrenalectomy., Conclusion: Incidence and risk of postoperative AKI were significantly higher in PA patients after surgical treatment. High ACR on the tumor side and high LI were associated with higher risk of AKI in PA patients compared to pheochromocytoma patients., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest. This material has not been published previously and will not be submitted for publication elsewhere., (Copyright © 2019 The Korean Society of Electrolyte Metabolism.)