Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Seasonality in hip fracture among haemodialysis patients and kidney transplant recipients in South Korea.

AIM: The seasonality of hip fracture in haemodialysis (HD) patients and kidney transplant recipients (KTRs) have not been reported. We assessed seasonal variations in hip fractures among patients with end-stage kidney disease who undergo maintenance HD and KTRs. METHODS: Using the Korean National Health Insurance System database from January 2012 to December 2017, monthly counts of hip fracture were calculated among HD patients (n = 77 420) and KTRs (n = 8921). The 6-year normalized monthly fraction and seasonal fractions of hip fractures were calculated. A cosinor analysis was performed to determine the seasonality of the monthly incidence of hip fractures. RESULTS: The 6-year average monthly fraction of hip fractures was lowest in June and highest in October in HD patients, and lowest in February and highest in November in KTRs. The 6-year average seasonal fraction among HD patients was lowest in summer and highest in winter, and lowest in summer and highest in autumn among KTRs, but there was no significant difference. The incidence ratio of hip fractures was lowest in June and highest in January in HD patients, and lowest in August and highest in November in KTRs. On cosinor analysis, HD patients showed significant seasonality in hip fracture incidence, with a trough in summer and a peak in winter (p = .031), whereas KTRs did not exhibit a significant trend (p = .44). CONCLUSION: Hip fractures occurred more frequently in winter and less frequently in summer in patients undergoing HD, whereas KTRs did not show a seasonal trend.

The combined prognostic significance of alkaline phosphatase and vascular calcification in patients with end-stage kidney disease.

BACKGROUND AND AIMS: Little is known about the interaction between serum alkaline phosphatase (ALP) and vascular calcification (VC) affecting cardiovascular events (CVE) and mortality in end-stage kidney disease (ESKD) patients. This study investigated the combined effect of ALP and VC on prognosis in ESKD patients starting dialysis. METHODS AND RESULTS: Data from 587 ESKD patients treated at a single center between January 2006 and July 2017 were retrospectively evaluated. VC was assessed by the aortic calcification index (ACI) using abdominal computed tomography. Patients were stratified into four groups according to the median ACI (17.18) and serum ALP value (108.0 U/L) as low ACI-low ALP, low ACI-high ALP, high ACI-low ALP, or high ACI-high ALP. The association between ALP and VC and the composite of CVE and death was analyzed. During a median follow-up of 3.1 years (range, 1.5-5.6 years), 140 patients (23.8%) developed CVE and 130 deaths (22.1%) occurred. In the stratified analysis, patients with high ACI-low ALP had a greater risk of the composite endpoint than patients with low ACI-low ALP (adjusted hazard ratio, 2.09; 95% confidence interval, 1.58-2.60; P = 0.004). Patients with high ACI-high ALP had the greatest risk (adjusted hazard ratio, 2.25; 95% confidence interval, 1.77-2.72; P = 0.001). The interaction between ACI and ALP on CVE and mortality was statistically significant (P < 0.05). CONCLUSIONS: The combined effect of VC and higher ALP was associated with a greater risk of CVE and death, and high serum ALP amplified the risk associated with VC in ESKD patients starting dialysis.

Factors associated with low trabecular bone scores in patients with end-stage kidney disease.

The trabecular bone score (TBS) is a textural index that indirectly assesses bone trabecular microarchitecture using lumbar spine images obtained by dual-energy X-ray absorptiometry (DXA). This study compared the TBS of patients with end-stage kidney disease (ESKD) with that of matched controls to identify risk factors associated with a low TBS. TBS and bone mineral density (BMD) were assessed in ESKD patients (n = 76) and age- and sex-matched control subjects (n = 76) using DXA. The TBS of both groups was then compared, and risk factors associated with a low TBS (defined as ≤ 1.31) were evaluated. The mean TBS in the ESKD group was significantly lower than that in the control group (1.34 ± 0.15 vs. 1.43 ± 0.08, respectively; p < 0.001). More subjects in the ESKD group had a low TBS [34.2% (ESRD) vs. 5.3% (controls); p < 0.001]. The TBS was negatively correlated with age, alkaline phosphatase and C-reactive protein levels, and dialysis vintage, and positively correlated with BMD at the lumbar spine, femoral neck, and hip. Multivariate analysis identified lower estimated glomerular filtration rate and increased C-reactive protein levels as being significantly associated with a low TBS. In conclusion, ESKD patients had abnormal bone microarchitecture (as assessed by the TBS). The TBS was positively correlated with BMD. Renal function and inflammatory marker levels were independently associated with a low TBS. Thus, TBS may be a useful clinical tool for assessing cancellous bone connectivity in ESKD patients.

Bioimpedance spectroscopy-guided fluid management in peritoneal dialysis patients with residual kidney function: A randomized controlled trial.

AIM: Bioimpedance spectroscopy (BIS) allows volume status to be assessed objectively. This study evaluated the effect of BIS-guided fluid management on residual kidney function (RKF), volume status, and cardiovascular events in peritoneal dialysis (PD) patients. METHODS: A multicenter, prospective, randomized, controlled trial was conducted over 12 months in 2013-2017. Non-anuric PD patients (urine volume ≥ 500 mL/day) were randomized to clinical method-guided management (n = 98) or BIS-guided management (n = 103). The volume in the BIS group was controlled with BIS, with the aim of achieving the target overhydration (OH) goal of -2.0 to +2.0 L. The volume in the control group was controlled by clinical assessment alone. The groups were compared in terms of change in RKF and volume status at 12 months relative to baseline and in terms of cardiovascular event rates during a median follow-up period of 36 months. RESULTS: Compared with the controls, the BIS group did not show a significant improvement in change in OH, after adjustments were made for covariates (P = 0.191). The two groups did not differ in terms of delta OH, renal creatinine and urea clearance, and 24 h urine volume. The control and BIS groups also did not differ significantly in terms of change in peritoneal ultrafiltration volume, blood pressure, body weight and echocardiographic variables or in cardiovascular event rates (10.2% vs 11.3%; P = 0.953). CONCLUSION: Bioimpedance spectroscopy-guided fluid management did not show an additional benefit to achieve euvolemia, and did not affect the decline in RKF in non-anuric PD patients.

The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 Diabetes.

Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase kinase-ß (CaMKKß) and numbers of phosphorylated liver kinase B1 (LKB1)- and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKKß, phosphorylated Ser431LKB1, phosphorylated Thr172AMPK, and PPARα expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose-treated human GECs and murine podocytes, AdipoRon increased intracellular Ca2+ levels that activated a CaMKKß/phosphorylated Ser431LKB1/phosphorylated Thr172AMPK/PPARα pathway and downstream signaling, thus decreasing high-glucose-induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARα pathway, suggesting its efficacy for treating type 2 diabetes-associated DN.

Prognostic Utility of Soluble Suppression of Tumorigenicity 2 level as a Predictor of Clinical Outcomes in Incident Hemodialysis Patients.

Background: The suppression of tumorigenicity 2 (ST2) is associated with cardiac remodeling and tissue fibrosis. It is well known as a novel biomarker on predictor of cardiovascular events in patients with heart failure. In patients needed to start dialysis treatment, most of them had congestive heart failure. However, the prognostic implications of serum ST2 level are unknown in incident hemodialysis patients. Methods: A total 182 patients undergoing incident hemodialysis were consecutively enrolled from November 2011 to December 2014. These patients were classified into two groups according to their median ST2 levels. The two groups were subsequently compared with respect to their major adverse cerebro-cardiovascular events (MACCE) including all-cause mortality, heart failure admission, acute coronary syndrome, and nonfatal stroke. Results: The median duration of follow up was 628 days (interquartile range 382 to 1,052 days). ST2 was significant correlated with variable echocardiographic parameters. The parameters of diastolic function, deceleration time of the early filing velocity and maximal tricuspid regurgitation velocity were independently associated with the ST2 levels. High ST2 group had significantly higher incidence of all-cause mortality, and MACCE. High ST2 was a significant independent predictor of MACCE (adjusted hazard ratio 2.33, 95% confidence interval 1.12 to 4.87, p=0.024). Conclusion: The ST2 is associated with diastolic function and may be a predictor of clinical outcomes in incident hemodialysis patients.

Vascular calcification and left ventricular hypertrophy in hemodialysis patients: interrelationship and clinical impacts.

Background: We examined the relationship and combined effect of vascular calcification (VC) and left ventricular hypertrophy (LVH) on deaths and cardiovascular events (CVEs) in hemodialysis (HD) patients. Methods: Maintenance HD patients (n=341) were included. Echocardiography data and plain chest radiographs were used to assess LVH and aortic arch VC. Results: VC was found in 100 patients (29.3%). LVH was more prevalent in patients with VC compared with those without VC (70% vs. 50.2%, P=0.001). VC was independently associated with a 2.42-fold increased risk of LVH (95% CI, 1.26-4.65). In multivariate analysis, compared with patients with neither VC nor LVH, the coexistence of VC and LVH was independently associated with CVE (HR, 2.01; 95% CI, 1.09-3.72), whereas VC or LVH alone was not. Patients with both VC and LVH had the highest risk for a composite event of deaths or CVE (HR, 1.88; 95% CI, 1.15-3.06). Significant synergistic interaction was observed between VC and LVH (P for interaction=0.039). Conclusions: VC was independently associated with LVH. The coexistence of VC and LVH was associated with higher risk of deaths and CVEs than either factor alone. VC and LVH showed a synergistic interaction for the risk of deaths and CVEs.

The Clinical Usefulness of Measurement of Visceral Fat Area Using Multi-Frequency Bioimpedance: The Association with Cardiac and Renal Function In General Population with Relatively Normal Renal Function.

Background: This study was performed to determine the clinical usefulness of measurement of visceral fat area (VFA) using bioimpedance analysis in relation with left ventricular hypertrophy (LVH), diastolic dysfunction parameters, and decreased estimated glomerular filtration rate (eGFR). Methods: A cross-sectional analysis was performed on 1028 patients with eGFR≥60 ml/min/1.73m2, aged 40 - 64 years, and who underwent routine health check-ups. Subjects were divided into tertiles based on their VFA. Associations of VFA with echocardiographic parameters and eGFR were evaluated. Results: Across the VFA teriltes, there was a significant trend for increasing left ventricular mass index (LVMi), left atrial diameter (LAD), and ratio of early mitral inflow velocity to peak mitral annulus velocity (E/E' ratio) and that for decreasing ratio of early to late mitral inflow peak velocities (E/A ratio) and eGFR. In multivariate linear regression analysis, log-transformed VFA was significantly associated with increased LVMi, LAD, and E/E' ratio, and with decreased E/A ratio and eGFR. After adjustment for body mass index, log-transformed VFA remained as a significant determinant for E/A ratio. Conclusion: VFA may be associated with LV structure and diastolic function, and decreased eGFR in middle-aged adults with normal or mildly impaired renal function.

Gender-Specific Associations between Low Skeletal Muscle Mass and Albuminuria in the Middle-Aged and Elderly Population.

Objective This study assessed gender-specific associations between low muscle mass (LMM) and albuminuria. Methods Data from the Korea National Health and Nutrition Examination Survey 2011 were employed. The study consisted of 1,087 subjects (≥50 years old). Skeletal muscle index (SMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Mild LMM and severe LMM were defined as SMI that were 1-2 and >2 standard deviations below the sex-specific mean appendicular skeletal muscle mass of young adults, respectively. Increased albuminuria was defined as albumin-to-creatinine ratio ≥30mg/g Results Men with mild and severe LMM were significantly more likely to have increased albuminuria (15.2% and 45.45%, respectively) than men with normal SMI (9.86%, P<0.0001), but not women. Severe LMM associated independently with increased albuminuria in men (OR=7.661, 95% CI=2.72-21.579) but not women. Severe LMM was an independent predictor of increased albuminuria in hypertensive males (OR=11.449, 95% CI=3.037-43.156), non-diabetic males (OR=8.782, 95% CI=3.046-25.322), and males without metabolic syndrome (MetS) (OR=8.183, 95% CI=1.539-43.156). This was not observed in males without hypertension, males with diabetes or MetS, and all female subgroups. Conclusion Severe LMM associated with increased albuminuria in men, especially those with hypertension and without diabetes or MetS.

Serum gamma-glutamyltransferase is not associated with subclinical atherosclerosis in patients with type 2 diabetes.

BACKGROUND: This study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes. METHODS: This cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (≥1720 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50 % of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed. RESULTS: Serum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles. CONCLUSIONS: Serum GGT levels were significantly associated with obesity, atherogenic dyslipidaemia, and metabolic syndrome, but not with the early and late stages of atherosclerotic vascular changes, in patients with type 2 diabetes. Serum GGT level may not be a reliable marker of subclinical atherosclerosis in type 2 diabetes.

Overhydration Negatively Affects Quality of Life in Peritoneal Dialysis Patients: Evidence from a Prospective Observational Study.

UNLABELLED: Backgound: This study evaluated whether the hydration status affected health-related quality of life (HRQOL) during 12 months in peritoneal dialysis (PD) patients. METHODS: The hydration status and the HRQOL were examined at baseline and after 12 months using a bioimpedance spectroscopy and Kidney Disease Quality of Life-Short Form, respectively in PD patients. Four hundred eighty-one patients were included and divided according to the baseline overhydration (OH) value; normohydration group (NH group, -2L≤ OH ≤+2L, n=266) and overhydration group (OH group, OH >+2L, n=215). Baseline HRQOL scores were compared between the two groups. The subjects were re-stratified into quartiles according to the OH difference (OH value at baseline - OH value at 12 months; <-1, -1 - -0.1, -0.1 - +1, and ≥+1L). The relations of OH difference with HRQOL scores at 12 months and the association of OH difference with the HRQOL score difference (HRQOL score at baseline - HRQOL score at 12 months) were assessed. RESULTS: The OH group showed significantly lower baseline physical and mental health scores (PCS and MCS), and kidney disease component scores (KDCS) compared with the NH group (all, P<0.01). At 12 months, the adjusted PCS, MCS, and KDCS significantly increased as the OH difference quartiles increased (P<0.001, P=0.002, P<0.001, respectively). In multivariate analysis, the OH difference was independently associated with higher PCS (ß = 2.04, P< .001), MCS (ß=1.02, P=0.002), and KDCS (ß=1.06, P<0.001) at 12 months. The OH difference was independently associated with the PCS difference (ß = -1.81, P<0.001), MCS difference (ß=-0.92, P=0.01), and KDCS difference (ß=-0.90, P=0.001). CONCLUSION: The hydration status was associated with HRQOL and increased hydration status negatively affected HRQOL after 12 months in PD patients.

Pre-existing Arterial Micro-Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients.

Vascular access micro-calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vascular access patency is still undetermined. Our study aimed to determine the impact of arterial micro-calcification (AMiC) on the patency of vascular access in HD patients. One-hundred fourteen HD patients receiving arteriovenous fistula (AVF) operation were included in this study. During the operation, we obtained partial arterial specimen and performed pathological examination by von Kossa stain to identify AMiC. We compared primary unassisted AVF failure within 1 year between positive and negative AMiC groups, and performed Cox regression analysis for evaluating risk factor of AVF failure. The incidence of AMiC was 37.7% and AVF failure occurred in 45 patients (39.5%). The AVF failure rate within 1 year was greater in the positive AMiC group than those in the negative AMiC group (53.5% vs. 31.0%, p = 0.02). Kaplan-Meier analysis showed that the positive AMiC group had a lower AVF patency rate than the negative AMiC group (p = 0.02). The presence of AMiC was an independent risk factor for AVF failure. In conclusion, preexisting AMiC of the vascular access is associated with primary unassisted AVF failure in incident HD patients.

Diagnostic utility of immunochemical fecal occult blood tests to detect lower gastrointestinal lesions in patients with chronic kidney disease.

PURPOSE: The immunochemical fecal occult blood test (iFOBT) is a useful method to screen for lower gastrointestinal (GI) bleeding-related lesions. However, few studies have investigated the diagnostic utility of iFOBT in chronic kidney disease (CKD). METHODS: We included 691 patients with nondialysis-dependent CKD stages 2-5 or those receiving dialysis. Bleeding-related lower GI lesions were identified by colonoscopy, and the diagnostic utility of iFOBT was evaluated. RESULTS: Bleeding-related lower GI lesions were found in 9.2% of 491 patients with CKD stage 2, 17.8% of 107 patients with CKD stage 3/4, and 25.8% of 93 patients with CKD stage 5/dialysis (p < 0.001). Compared with CKD stage 2, CKD stage 5/dialysis was independently associated with a 2.80-fold risk for bleeding-related lesions (p = 0.019). The iFOBT was positive in 92 (13.3%) patients and the area under the receiver operating curve (AUC) for a bleeding-related lesion was 0.64 (p < 0.001). The sensitivity of iFOBT increased as the CKD stage worsened (20.0 vs 52.6 vs 58.3%; p = 0.002). However, the specificity to detect bleeding-related lesions decreased with the severity of CKD stage (94.6 vs. 78.4 vs. 76.8%; p < 0.001). The AUC of iFOBT to detect adenoma or carcinoma was 0.54 (p = 0.046), and a similar pattern of sensitivity and specificity was observed between different CKD stages. CONCLUSIONS: The prevalence of bleeding-related lower GI lesions and the sensitivity of iFOBT to detect these GI lesions increased in advanced CKD. However, iFOBT should be used cautiously in these patients because its specificity decreased.

Fimasartan, a Novel Angiotensin-Receptor Blocker, Protects against Renal Inflammation and Fibrosis in Mice with Unilateral Ureteral Obstruction: the Possible Role of Nrf2.

OBJECTIVES: A newly developed angiotensin II receptor blocker, fimasartan, is effective in lowering blood pressure through its action on the renin-angiotensin system. Renal interstitial fibrosis, believed to be due to oxidative injury, is an end-stage process in the progression of chronic kidney disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to regulate cellular oxidative stress and induce expression of antioxidant genes. In this study we investigated the role of Nrf2 in fimasartan-mediated antioxidant effects in mice with renal fibrosis induced by unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: UUO was induced surgically in mice, followed by either no treatment with fimasartan or the intraperitoneal administration of fimasartan (3 mg/kg/day). On day 7, we evaluated the changes in the renin-angiotensin system (RAS) and the expression of Nrf2 and its downstream antioxidant genes, as well as renal inflammation, apoptosis, and fibrosis in the obstructed kidneys. The effect of fimasartan on the Nrf2 pathway was also investigated in HK-2 cells stimulated by tumor necrosis factor-α. RESULTS: The mice with surgically induced UUO showed increased renal inflammation and fibrosis as evidenced by histopathologic findings and total collagen content in the kidney. These effects were attenuated in the obstructed kidneys of the fimasartan-treated mice. Fimasartan treatment inhibited RAS activation and the expression of Nox1, Nox2, and Nox4. In contrast, fimasartan upregulated the renal expression of Nrf2 and its downstream signaling molecules (such as NQO1; HO-1; GSTa2 and GSTm3). Furthermore, it increased the expression of antioxidant enzymes, including CuSOD, MnSOD, and catalase. The fimasartan-treated mice had significantly less apoptosis on TUNEL staining, with decreased levels of pro-apoptotic protein and increased levels of anti-apoptotic protein. In the HK-2 cells, fimasartan treatment inhibited RAS activation, decreased expression of mitogen-activated protein kinases (MAPKs), and upregulated the Nrf2 pathway. CONCLUSIONS: These results suggest that fimasartan has beneficial effects in reducing renal oxidative stress, inflammation, and fibrosis. Possible mechanisms to explain these effects are inhibition of RAS and MAPKs and upregulation of Nrf2 signaling, with subsequent induction of antioxidant pathways.

Effects on g2/m phase cell cycle distribution and aneuploidy formation of exposure to a 60 Hz electromagnetic field in combination with ionizing radiation or hydrogen peroxide in l132 nontumorigenic human lung epithelial cells.

The aim of the present study was to assess whether exposure to the combination of an extremely low frequency magnetic field (ELF-MF; 60 Hz, 1 mT or 2 mT) with a stress factor, such as ionizing radiation (IR) or H2O2, results in genomic instability in non-tumorigenic human lung epithelial L132 cells. To this end, the percentages of G2/M-arrested cells and aneuploid cells were examined. Exposure to 0.5 Gy IR or 0.05 mM H2O2 for 9 h resulted in the highest levels of aneuploidy; however, no cells were observed in the subG1 phase, which indicated the absence of apoptotic cell death. Exposure to an ELF-MF alone (1 mT or 2 mT) did not affect the percentages of G2/M-arrested cells, aneuploid cells, or the populations of cells in the subG1 phase. Moreover, when cells were exposed to a 1 mT or 2 mT ELF-MF in combination with IR (0.5 Gy) or H2O2 (0.05 mM), the ELF-MF did not further increase the percentages of G2/M-arrested cells or aneuploid cells. These results suggest that ELF-MFs alone do not induce either G2/M arrest or aneuploidy, even when administered in combination with different stressors.

Clinical significance of chronic kidney disease and atrial fibrillation on morbidity and mortality in patients with acute myocardial infarction.

BACKGROUND/AIMS: Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined. METHODS: Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE). RESULTS: The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015). CONCLUSION: The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk.

Association of blood manganese level with diabetes and renal dysfunction: a cross-sectional study of the Korean general population.

BACKGROUND: The purpose of this study was to evaluate the association between blood manganese levels and the prevalence of chronic diseases in the Korean population. METHODS: This was a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNAHNES). The study included 3996 participants 20 years of age or older whose blood manganese levels had been measured. The participants were also evaluated for the presence of five chronic diseases: diabetes, renal dysfunction, hypertension, ischemic heart disease, and stroke. RESULTS: Blood manganese levels were significantly lower in the diabetes group compared with the non-diabetes group (1.26 ± 0.02 vs. 1.35 ± 0.01 µg/dL; p = 0.001) and the renal dysfunction group compared with those with normal renal function (1.28 ± 0.03 vs. 1.35 ± 0.01 µg/dL; p = 0.04). There was no significant association between blood manganese levels and the presence of ischemic heart disease or stroke. A multivariate logistic regression analysis adjusted for age, sex, and body mass index was performed; the odds ratio was 0.652 (95% CI: 0.46-0.92) for diabetes and 0.589 (95% CI: 0.39-0.88) for renal dysfunction when comparing the higher quartiles (Q2-4) with the lowest quartile (Q1) of blood manganese level. The prevalence of diabetes was 7.6% in Q1 and 5.3% in Q2-4 (p = 0.02). Similarly, the prevalence of renal dysfunction was 6.8% in Q1, compared with 4.6% in Q2-4 (p = 0.02). CONCLUSION: The prevalence of diabetes and renal dysfunction increased in participants with low blood manganese levels, suggesting that blood manganese may play a role in glucose homeostasis and renal function.

Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. METHODS: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. RESULTS: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (ß = -5.77, p = 0.001), baseline renal function (ß = -0.12, p < 0.001) and level of proteinuria (ß = -2.36, p = 0.015) were independently associated with the rate of renal function decline. CONCLUSIONS: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.

Blood lead and cadmium levels and renal function in Korean adults.

BACKGROUND: The objective of this study was to evaluate the associations of blood lead and cadmium levels with estimated glomerular filtration rate (eGFR) and proteinuria in Korean adults. METHODS: This was a cross-sectional study based on the Korea Nation Health and Nutrition Examination Survey (KNHANES) to analyze the association of blood lead and cadmium levels with renal dysfunction and urine protein excretion. We defined renal dysfunction as eGFR < 60 ml/min/1.73 m(2), as measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and proteinuria as positive urine dip-stick result. RESULTS: Blood lead and cadmium levels were significantly increased in the renal dysfunction group compared with the normal renal function group. Lead levels were significantly higher in the proteinuria group than in the group with no proteinuria. There were no differences in cadmium levels according to the amount of proteinuria. Multivariate logistic regression analysis adjusted for age and sex demonstrated higher lead and cadmium levels in the renal dysfunction group than in the group with normal renal function [odds ratio (OR) 1.344, 95 % confidence interval (CI) 1.157-1.162, P < 0.05; OR 1.467, 95 % CI 1.077-1.999, P < 0.05, respectively]. For proteinuria, the fully adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles were 1.22 (95 % CI 1.00-1.50) and 0.51 (95 % CI 0.24-1.08), respectively, showing no significance. For reduced eGFR, the fully adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles were 1.23 (95 % CI 0.98-1.53) and 1.93 (95 % CI 1.39-2.67), respectively, showing the significant association between lead and cadmium levels and renal function. The risk of having reduced eGFR for individuals in the highest quartiles of both lead and cadmium levels in blood was greater than for those in the highest quartile of blood level of lead or cadmium only. CONCLUSION: The CKD-EPI equation showed that blood lead and cadmium levels were associated with renal dysfunction in the Korean adult population. This finding has significant implications for environmental institutional strategies regarding heavy metal exposure.