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Although renal dysfunction is associated with a higher incidence of malignancies, there is no research on the incidence of specific types of digestive cancer in pre-dialytic chronic kidney disease (CKD) patients compared to the general population. This study was conducted on newly diagnosed pre-dialytic CKD patients (n = 35,443) between 2003 and 2013 using the National Health Insurance Service-National Sample Cohort in Korea. The risk of digestive cancer development in pre-dialytic CKD patients was calculated as the standardized incidence ratio (SIR). During a median follow-up of 54.9 months, the risk of digestive cancer in CKD patients was significantly higher than in the cohort population [SIR; 1.54, 95% confidence interval (95% CI); 1.46-1.62], the SIR of pancreatic cancer was 2.21, and the SIRs of hepatoma, colorectal cancer (CRC), bile duct cancer, and gastric cancer were 2.01, 1.60, 1.40, and 1.25, respectively. Moreover, in CKD patients younger than 40 years, the incidence ratios of hepatoma and CRC were remarkably larger compared with the cohort population of the same age (SIR; 5.98 in hepatoma, 4.58 in CRC). However, the incidence of specific types of digestive cancer seemed to be similar, irrespective of sex. In conclusion, digestive cancers were more frequently observed in CKD-diagnosed patients compared with a cohort population in Korea, which suggests that physicians should closely monitor their patients for the incidence of digestive cancer when they are diagnosed with CKD.

Klotho is a soluble or membrane-bound anti-aging protein, whose protective actions are important for a prudential function of many organs. Because Klotho and cerebral small vessel disease (SVD) are associated with ageing process and endothelial dysfunction, it is possible that Klotho has an association with cerebral SVD. We aimed to investigate the association of plasma Klotho concentration with the presence, burden and progression of cerebral SVD. We prospectively enrolled 262 patients with first-ever acute cerebral infarction, performed brain MRI and collected their blood samples within 24 hours of admission. An enzyme-linked immunosorbent assay was used for evaluating plasma Klotho concentration. We estimated the total SVD score of each patient after determining the presence and burden of high-grade white matter hyperintensities (HWMHs), cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and asymptomatic lacunar infarctions (ALIs). Univariate and multivariate analyses were conducted to investigate association of Klotho with cerebral SVD and the total SVD score. Of the 262 patients, 152 (58.0%) were men. The mean age of these patients was 64.7 years. The mean ± standard deviation of plasma Klotho concentration was 329.8 ± 194.1 pg/mL. In multivariate analysis, plasma Klotho concentration was negatively associated with the presence of HWMHs [Odds ratio (OR): 0.13, p = 0.047], HPVSs (OR: 0.22, p = 0.024) and ALIs (OR: 0.53, p = 0.021) but not associated with the presence of CMBs (OR: 0.39, p = 0.404). Plasma Klotho concentration was also negatively related to the total SVD score (unstandardized coefficients beta: -0.895, standard error = 0.317, p = 0.005, R2 = 0.239). Furthermore, plasma Klotho concentration was negatively related to the presence (OR: 0.75, 95% CI: 0.59-0.96, p = 0.025) and severity of cerebral SVD progression (OR: 0.72, 95% CI: 0.56-0.92, p = 0.009). In conclusion, plasma Klotho concentration was negatively associated with the presence, burden and progression of cerebral SVD.

Appropriate dietary adjustment in patients with chronic kidney disease (CKD) is important, and nutritional guidelines recommend different dietary management depending on the CKD stage. However, there is no study, to our knowledge, of the characteristics of dietary intake according to CKD stages. We tried to assess the comparison of nutritional intake according to CKD stages. A cross-sectional study was conducted to reveal the characteristics of dietary intake among patients with CKD based on the Korean National Health and Nutritional Examination Survey between 2011 and 2014. Of 16,878 participants, we classified non-CKD (n = 14,952) and CKD (n = 1,926), which was stratified into five groups (I, II, IIIa, IIIb, and IV–V). We investigated the characteristics of dietary intake, such as energy, water, protein, fat, carbohydrate, sodium, potassium, calcium, and phosphorus, according to stage of CKD. We also explored nutritional intake according to CKD stage among patients with early CKD (stage I and II) and advanced CKD (stage IIIa, IIIb, and IV–V). Intake of majority of nutrients and energy tended to be decreased as CKD progressed. In early CKD stage, intake of energy, water, protein, fat, carbohydrate, potassium, calcium and phosphorus seemed to be statistically significant decreased as CKD progressed. In advanced CKD stage, intake of potassium and calcium seemed to be decreased as CKD progressed, but the intake of energy was about to be lower limit. Appropriate dietary education and CKD recognition are needed to improve nutritional intake depending on the CKD stage.

The time at which hypertension treatment should be initiated for different age groups and sexes remains controversial. We aimed to determine whether the association between blood pressure (BP) and major adverse cardiovascular events (MACE) varies with age and sex. This study enrolled 327,328 subjects who had not taken antihypertensive medication in the Korean National Health Service-National Health Screening Cohort between 2002 and 2003. Participants were categorized into four groups according to 2017 American College of Cardiology/American Heart Association hypertension guideline. Primary outcome was MACE characterized by cardiovascular mortality, myocardial infarction, unstable angina, and stroke. During a 10-year follow-up, a significant increase in MACE risk was observed from the stage 1 hypertension group (hazard ratio [HR], 1.23; 95% CI 1.15–1.32; P  < 0.001) in time-varying Cox analysis. This relationship was persistent in subjects aged < 70 years, but increased MACE risk was observed only in the stage 2 hypertension group in ≥ 70 years (HR, 1.52; 95% CI 1.32–1.76, P  < 0.001). When categorized as per sex, both men and women showed significant MACE risk from stage 1 hypertension. However, on comparing the sexes after stratifying by age, a significantly increased risk of MACE was shown from stage 1 hypertension in men aged < 50 years, but from stage 2 hypertension in men aged ≥ 50 years. Meanwhile, increased MACE risk was observed from stage 2 hypertension in women aged < 60 years, but from stage 1 hypertension in women aged ≥ 60 years. Thus, young male subjects had higher MACE risk than young female subjects, but this difference gradually decreased with age and there was no difference between sexes in subjects aged ≥ 70 years. Therefore, our results suggest that hypertension treatment initiation may need to be individualized depending on age and sex.

There has been paucity of data regarding the secular trend of adverse outcomes in peritoneal dialysis (PD) as compared with hemodialysis (HD) in Korea. 96,596 patients who started dialysis between 2004–2015 in Korea were identified using the National Health Insurance Service database. The adjusted hazard ratio (HR) (95% confidence interval, CI) of PD over HD for mortality was 1.31 (1.27–1.36; P  < 0.001) in the period of 2004–2007 and 1.21 (1.16–1.27; P  < 0.001) in the period of 2008–2011. However, the hazard of PD over HD for mortality turned out to be insignificant in the period of 2012–2015. Similar trend was noted for nonfatal cardiovascular events (CVEs). In subgroup analysis, the hazard of PD over HD for mortality was evident, regardless of the status of age, diabetes, and comorbidity burden in 2004–2011. In 2012–2015, however, the hazard of PD over HD for mortality was insignificant when follow up was censored at one year, which became significant when follow up follow up was censored at three or five year. In conclusion, the mortality of PD over HD in Korea has been significantly improved, a finding that was paralleled by the improved nonfatal CVEs.

Only a few observational studies investigated the association between hypochloremia and mortality in critically ill patients, and these studies included small number of septic patients. Also, no study has evaluated the effect of an increase in chloride (Cl − ) concentration in hypochloremia on the mortality. A total of 843 Korean septic patients were divided into three groups based on their baseline Cl − level, and Cox analyses were performed to evaluate the 28-day mortality. Moreover, the change in Cl − level (ΔCl) from baseline to 24, 48, or 72 hour was determined, and Cox analyses were also conducted to evaluate the relationship of ΔCl with mortality. 301 (35.7%) patients were hypochloremic (Cl −  < 97 mEq/L), and 38 (4.5%) patients were hyperchloremic (Cl −  > 110 mEq/L). During the follow-up period, 119 (14.1%) patients died. Hypochloremia was significantly associated with an increased mortality after adjusting for several variables, but an 1 mEq/L increase of ΔCl within 24 hour in patients with hypochloremia was significantly related to a decreased mortality. Caution might be required in severe septic patients with hypochloremia considering their increased mortality rate. However, an increased Cl − concentration might decrease the mortality rate of such patients.

Background/Aims: Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN). Methods: We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline. Results: Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P< 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome. Conclusion: The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents.

Fluid balance is a critical prognostic factor for patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated whether repeated fluid balance monitoring could improve prognosis in this clinical population. This was a multicenter retrospective study that included 784 patients (mean age, 67.8 years; males, 66.4%) with severe AKI requiring CRRT during 2017–2019 who were treated in eight tertiary hospitals in Korea. Sequential changes in total body water were compared between patients who died (event group) and those who survived (control group) using mixed-effects linear regression analyses. The performance of various machine learning methods, including recurrent neural networks, was compared to that of existing prognostic clinical scores. After adjusting for confounding factors, a marginal benefit of fluid balance was identified for the control group compared to that for the event group ( p  = 0.074). The deep-learning model using a recurrent neural network with an autoencoder and including fluid balance monitoring provided the best differentiation between the groups (area under the curve, 0.793) compared to 0.604 and 0.606 for SOFA and APACHE II scores, respectively. Our prognostic, deep-learning model underlines the importance of fluid balance monitoring for prognosis assessment among patients receiving CRRT.

Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.

Although C1q nephropathy (C1qN) was introduced three decades ago, the clinical significance and renal outcomes of C1qN remain unclear. This study aimed to evaluate the clinical characteristics of C1qN, including renal outcomes, by performing a matched comparison within a multicenter cohort. We enrolled 6,413 adult patients who underwent kidney biopsy between January 2000 and January 2018 at three tertiary hospitals in Korea. We compared the clinical characteristics of 23 patients with C1qN with those of patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) who were matched by age, sex, diabetic status, and a period of biopsy. Histological and clinical parameters in patients with C1qN were also evaluated according to the different pathological phenotypes. For a mean follow-up period of 92 months, 4 patients with C1qN (17.4%) developed end-stage renal disease (ESRD). None of the matched patients with MCD had ESRD, but 7 (30.4%) of patients with FSGS progressed to ESRD, which was not different from that of C1qN patients (p = 0.491). Laboratory and pathological findings, except segmental glomerulosclerosis, were not notably different between FSGS and C1qN. The presence of segmental glomerulosclerosis, mesangial hypercellularity, and podocyte effacement did not affect both the short- and long-term renal outcomes in patients with C1qN. Our study showed that the renal outcomes of C1qN are comparable with those of FSGS, and not with MCD. Specific pathological findings, including segmental glomerulosclerosis in C1qN, were not associated with renal outcomes, which may suggest homogeneity in the clinical features of C1qN.