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BACKGROUND Lemierre's syndrome is a disease that causes anaerobic sepsis, internal jugular vein thrombosis, and septic embolism in the lungs and other organs after acute oropharyngeal infection. It was named after Andre-Alfred Lemierre in 1936. CASE SUMMARY Here, we have reported a case of Lemierre's syndrome in a 56-year-old female patient who presented with a sore throat. The patient had septic shock, had not voided, and had severe hyperglycemia at the time of her visit. Imaging tests revealed bilateral pneumonia, pleural effusion, pulmonary embolism, and renal vein thrombosis. The patient was admitted to the intensive care unit and placed on mechanical ventilation due to acute respiratory distress syndrome. Continuous renal replacement therapy was administered to treat renal failure with anuria. Klebsiella pneumoniae was cultured from blood and sputum samples. After reviewing various results, the patient was ultimately diagnosed with Lemierre's syndrome. The patient was treated with appropriate antibiotics and thrombolytic agents. She was discharged from the hospital after recovery. CONCLUSION Lemierre's syndrome is associated with a high mortality rate. Therefore, clinicians should be familiar with the signs and symptoms of this disease as well as the preemptive examinations, procedures, and treatments.

Background: Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galac tosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. Methods: Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogen ic mechanism leading to fibrosis in diseased kidneys. Results: Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry dis ease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry dis ease mice compared to wild-type control and UUO mice. Conclusion: These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in en hanced renal fibrosis under the stimulus of UUO in Fabry disease.

Donepezil is a cholinesterase inhibitor used extensively to treat Alzheimer disease. The increased cholinergic activity is associated with adverse effects, therefore gastrointestinal symptoms, in cluding nausea, vomiting, and diarrhea, are common. Hypokalemia is a rare adverse event that occurs in less than 1% of donepezil-treated patients. Although hypokalemia of mild and moder ate grade does not present serious signs and symptoms, severe hypokalemia often results in prolonged hospitalization and mortality. Herein, we report a case of hypokalemia developed af ter the initiation of donepezil therapy for cognitive impairment.

Background : : Vascular calcification (VC) is a major component of mineral bone disorders in patients with endstage renal disease (ESRD). Bone metabolism is affected by various factors, including sex hormones. This study investigated whether there was a sex-specific relationship between VC and incident fracture in patients with ESRD. Methods : : This was a retrospective cohort study of dialysis patients from a single center. VC was assessed by the aortic calcification index (ACI) using abdominal computed tomography. Patients were grouped by sex and stratified into low or high ACI groups, according to the median ACI value. The association between ACI and incident fracture was analyzed. Results : : Data from 593 patients (male: n = 328, median ACI, 14.57; female: n = 265, median ACI, 19.44) were included. During a median follow-up of 36.7 months, 71 patients (12.0%) developed fractures. The fracturefree survival rate was significantly lower in the high ACI group versus the low ACI group, both in males (P = 0.021) and females (P = 0.001). In males, multivariate analysis showed that the high ACI group and ACI per se were not significant risks for fracture. However, in females, both the high ACI group (adjusted hazard ratio, 2.720; P = 0.003) and ACI per se (adjusted hazard ratio, 1.768; P = 0.035) were independently associated with fracture after adjustment for confounding variables. Conclusion : : VC was independently associated with incident fracture in female patients with ESRD. There may be a sex-specific relationship between VC and fracture in patients with ESRD.

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 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.

Background and aims There is a growing evidence demonstrating an association between dyslipidemia and progression of chronic kidney disease (CKD), but results on the effects of high-density lipoprotein cholesterol (HDL-C) on renal outcome have been conflicting. In this study, the relationship between HDL-C variability and the risk for progression to end-stage renal disease (ESRD) was investigated. Methods This study analyzed data of 4,283,318 subjects who were free of ESRD at the time of enrollment, received more than three medical examinations from 2009 to 2012, and were followed to the end of 2015, based on the Korean National Health Insurance Service database. HDL-C variability was measured using the standard deviation, coefficient of variation, average real variability and variability independent of the mean (VIM). Results A total of 2,095 new cases of ESRD were observed during a median follow up of 3.38 years. There was a graded association between higher HDL-C variability and incident ESRD. In the multivariable adjusted model, hazard ratio comparing the highest and lowest quartiles of VIM of HDL-C was 1.82 (95% confidence interval, 1.58–2.09). The results were consistent when the variability of HDL-C was modeled using standard deviation, coefficient of variation and average real variability and were independent of other confounding factors, including the presence of CKD. Conclusions HDL-C variability independently predicted an increased risk for developing ESRD. Our findings suggest that identification of HDL-C variability may help improve risk stratification for the prevention of ESRD.

ObjectivesContrast-enhanced ultrasound (CEUS) enables the assessment of real-time renal microcirculation. This study investigated CEUS-driven parameters as hemodynamic predictors for renal outcomes in patients with acute kidney injury (AKI).MethodsForty-eight patients who were diagnosed with AKI were prospectively enrolled and underwent CEUS at the occurrence of AKI. Parameters measured were the wash-in slope (WIS), time to peak intensity, peak intensity (PI), area under the time-intensity curve (AUC), mean transit time (MTT), time for full width at half maximum, and rise time (RT). The predictive performance of the CEUS-driven parameters for Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, initiation of renal replacement therapy (RRT), AKI recovery, and chronic kidney disease (CKD) progression was assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of CEUS.ResultsCortical RT (Odds ratio [OR] = 1.21) predicted the KDIGO stage 3 AKI. Cortical MTT (OR = 1.07) and RT (OR = 1.20) predicted the initiation of RRT. Cortical WIS (OR = 76.23) and medullary PI (OR = 1.25) predicted AKI recovery. Medullary PI (OR = 0.78) and AUC (OR = 1.00) predicted CKD progression. The areas under the ROC curves showed reasonable performance for predicting the initiation of RRT and AKI recovery. The sensitivity and specificity of the quantitative CEUS parameters were 60-83% and 62-77%, respectively, with an area under the curve of 0.69-0.75.ConclusionCEUS may be a supplemental tool in diagnosing the severity of AKI and predicting renal prognosis in patients with AKI.

Adequate fluid management plays an important role in decreasing cardiovascular risk in peritoneal dialysis (PD) patients. We evaluated whether strict volume control monitored by bioimpedance spectroscopy (BIS) affects cardiac function in PD patients. This study is a secondary analysis of a multicentre, prospective, randomized, controlled trial. Fluid overload was assessed by the average overhydration/extracellular water (OH/ECW) at baseline, 6 months and 12 months. Patients were categorized as time-averaged overhydrated (TA-OH/ECW ≥15%) or normohydrated (TA-OH/ECW

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

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.

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.

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males, higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio, and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients, 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level &gt, 7.0 mg/dL for males and &gt, 5.6 mg/dL for females, 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.

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

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.

The prevalence rate and the incidence rate of hemodialysis and functioning kidney transplant recipients have continuously increased; on the contrary, those of peritoneal dialysis have continuously decreased since 2006. Dialysis patients have been getting older and have been maintained on dialysis longer. Diabetic nephropathy was the leading cause of end stage renal disease. The type of hemodialysis vascular access has been stable during the last 5 years (arteriovenous fistulas 76%, arteriovenous grafts 16%, central venous catheters 8% at 2016). Peritoneal dialysis catheter was mostly inserted surgically (67%), and swan neck straight tip peritoneal dialysis catheter was the most commonly used (48%). Vascular access was managed by radiologists and surgeons, and the management was fragmented among them in the past. However, since the nephrologists became interested in and knowledgeable about the vascular access, they began to play roles in vascular access management. Vascular access has been mostly created by vascular surgeons (≈60%); tunneled central venous hemodialysis catheter insertion and endovascular intervention such as percutaneous transluminal angioplasty (PTA) and thrombectomy have been mostly performed by radiologists (≈70%). Tunneled hemodialysis catheter insertion and endovascular intervention by nephrologists have slowly but consistently increased. Recently, the number of central venous hemodialysis catheter insertion has decreased, and tunneled hemodialysis catheter has been inserted more than non-tunneled hemodialysis catheter, indicating that vascular access has been created timely and the vascular access team has been educated about and following international guidelines.

Besides lowering glucose, empagliflozin, a selective sodium-glucose cotransporter-2 (SGLT2) inhibitor, have been known to provide cardiovascular and renal protection due to effects on diuresis and natriuresis. However, the natriuretic effect of SGLT2 inhibitors has been reported to be transient, and long-term data related to diuretic change are sparse. This study was performed to assess the renal effects of a 12-week treatment with empagliflozin (3 mg/kg) in diabetic OLETF rats by comparing it with other antihyperglycemic agents including lixisenatide (10 μg/kg), a glucagon-like peptide receptor-1 agonist, and voglibose (0.6 mg/kg), an α-glucosidase inhibitor. At 12 weeks of treatment, empagliflozin-treated diabetic rats produced still high urine volume and glycosuria, and showed significantly higher electrolyte-free water clearance than lixisenatide or voglibose-treated diabetic rats without significant change of serum sodium level and fractional excretion of sodium. In empagliflozin-treated rats, renal expression of Na+-Cl- cotransporter was unaltered, and expressions of Na+/H+ exchanger isoform 3, Na+-K+-2Cl- cotransporter, and epithelial Na+ channel were decreased compared with control diabetic rats. Empagliflozin increased an expression of aquaporin (AQP)7 but did not affect AQP3 and AQP1 protein expressions in diabetic kidneys. Despite the increased expression in vasopressin V2 receptor, protein and mRNA levels of AQP2 in empagliflozin-treated diabetic kidneys were significantly decreased compared to control diabetic kidneys. In addition, empagliflozin resulted in the increased phosphorylation of AQP2 at S261 through the increased cyclin-dependent kinases 1 and 5 and protein phosphatase 2B. These results suggest that empagliflozin may contribute in part to polyuria via its regulation of sodium channels and AQP2 in diabetic kidneys.

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.

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

Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice.

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.

Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.

BACKGROUND Inflammatory activity of the artery can be assessed by measuring 18F-fluorodeoxyglucose (18F-FDG) uptake with positron emission tomography computed tomography (PET/CT). Improvement in vascular function after renal transplantation has been reported, but no studies have used 18F-FDG PET/CT to examine the changes in vascular inflammation. This study investigated the changes in the inflammatory activity in the carotid artery after renal transplantation in patients with chronic kidney disease (CKD). MATERIAL AND METHODS 18F-FDG PET/CT was performed before and at 4 months after transplantation. We quantified 18F-FDG uptake as the target-to-background ratio (TBR) in the carotid artery in 10 CKD patients. TBR was evaluated in the whole carotid artery (WH) and most-diseased segment (MDS), and the mean and maximum values were analyzed. The concentrations of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, plasminogen activator inhibitor-1, and endothelin-1, were measured. RESULTS Eight patients showed a decrease in mean or maximum TBR. The average mean or maximum TBRs in the WH and MDS of the right and left arteries were all reduced after transplantation. The average mean TBR for the right WH decreased significantly (% reduction [95% CI]) by -5.74% [-15.37, -0.02] (p=0.047). TBRs did not correlate significantly with cytokine concentrations. The changes in cytokine concentrations after transplantation varied. CONCLUSIONS 18F-FDG uptake by the WH and MDS tended to reduce after renal transplantation. Therefore, renal transplantation may confer an anti-inflammatory effect on carotid atherosclerosis in patients with CKD; however, this effect is not large enough to be demonstrated in this study with small sample size.

Although the mechanism of cyclosporine A (CsA)-induced renal injury remains to be fully elucidated, accumulating evidence suggests that oxidative stress is critical in producing CsA-induced structural and functional renal impairment. The present study investigated the effect of D-pinitol, a cyclitol present in soybean, on chronic CsA nephropathy. Male ICR mice were treated with vehicle, CsA (30 mg/kg/day), D-pinitol (50 mg/kg/day) or a combination of CsA and D-pinitol for 28 days. To assess which pathway responding to oxidative stress is augmented by D-pinitol, the expression levels of several antioxidant enzymes and their possible regulators were measured. Treatment with D-pinitol significantly suppressed the increase of serum creatinine and decrease of urine osmolality, compared with the CsA control group. Histological examination of Masson's trichrome- and α-smooth muscle actin-stained renal tissue demonstrated that the CsA-induced tubulointerstitial fibrosis and inflammation were attenuated by D-pinitol. Following the administration of D-pinitol, there were increased expression levels of heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, superoxide dismutase 1 and catalase in CsA-treated kidneys. In addition, D-pinitol increased the level of sirtuin 1 (Sirt1), and the total and nuclear expression levels of nuclear erythroid factor 2-related factor 2 (Nrf2), suggesting that activation of the Sirt1 and Nrf2 pathways may induce the cellular antioxi dant system against CsA-induced nephropathy. Collectively, these data suggested that D-pinitol may protect the kidney from CsA-induced fibrosis, and that this renoprotective effect of D-pinitol was due to the inhibition of oxidative stress through the activation of Sirt1 and Nrf2, and the subsequent enhancement of antioxidant enzymes.

Chronic kidney disease (CKD) and retinopathy share the common pathophysiology of microvascular dysfunction. It is unclear whether the clinical significance of diabetic retinopathy (DMR) and hypertensive retinopathy (HTNR) differs in CKD patients.We included 684 nondialysis-dependent CKD stage 3-5 patients with diabetes or hypertension: 501 patients with diabetes and 183 with hypertension. The clinical significance of DMR and HTNR was evaluated in terms of the rate of renal function decline and composite of any cardiovascular event or death.DMR was observed in 261 (52.1%) CKD patients with diabetes, and HTNR in 44 (24.0%) CKD patients with hypertension. In the diabetes group, the renal function decline rate was significantly steeper in patients with than in those without DMR (-7.4 ± 9.8mL/min/1.73m(2)/yr vs. -2.4 ± 7.6mL/min/1.73m(2)/yr; P0.001). In multivariate analysis, DMR were independently associated with a rapid decline in renal function (β=-2.44; P=0.20). However, HTNR did not affect the renal function decline in CKD patients. The composite event-free survival rate was lower in patients with diabetes and DMR than in those without DMR (P=0.043). Patients with diabetes and DMR were independently associated with a 2.13-fold increased risk for composite events (P=0.010). HTNR was not associated with higher risk for composite events in CKD patients.Coexistence of diabetes and DMR were independently associated with CKD progression and composite cardiovascular event/death, but the clinical significance of HTNR is less clear in CKD patients.

Background and aims This study evaluated the effects of resveratrol on arterial aging and the renin–angiotensin system (RAS) in mice and vascular smooth muscle cells (VSMCs). Methods Aging mice were divided into control and resveratrol groups. Histological changes, inflammation, oxidative stress, RAS components, and the expression of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), and anti-oxidative enzymes was measured in thoracic aortas of 24-month-old mice. The effect of resveratrol on fibrosis, cell senescence, and RAS components was also investigated in VSMCs stimulated by angiotensin (Ang) II. Results Aorta media thickness, inflammation, fibrosis, and oxidative stress were significantly lower in the resveratrol group than in the control group. Resveratrol treatment decreased serum Ang II level and the aortic expression of prorenin receptor (PRR) and angiotensin converting enzyme (ACE), and increased serum Ang-(1–7) level and the expression of ACE2, Ang II type 2 receptor (AT2R), and Mas receptor (MasR). Resveratrol increased the expression of phosphorylated AMPK, SIRT1, PGC-1α, phosphorylated endothelial nitric oxide synthase and superoxide dismutase 1 and 2, and decreased that of NADPH oxidase 2 and 4. In Ang II-stimulated VSMCs, resveratrol treatment markedly decreased the number of senescence associated β-galactosidase stained cells and pro-fibrotic protein expression and increased the expression of AT2R and MasR. Conclusions Resveratrol protects against arterial aging and this effect is associated with reduced activity of the PRR–ACE–Ang II axis and stimulation of the ACE2–Ang-(1–7)–ATR2–MasR axis.

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 Ca(2+)/calmodulin-dependent protein kinase kinase–β (CaMKKβ) 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 CaMKKβ, phosphorylated Ser(431)LKB1, phosphorylated Thr(172)AMPK, 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 Ca(2+) levels that activated a CaMKKβ/phosphorylated Ser(431)LKB1/phosphorylated Thr(172)AMPK/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 Ca(2+)/LKB1-AMPK/PPARα pathway, suggesting its efficacy for treating type 2 diabetes–associated DN.

Polymyositis is a rare and gradually progressive autoimmune disease of skeletal muscle. Two main types of renal involvement have been described: acute tubular necrosis related to rhabdomyolysis and glomerulonephritis. However, cases of overflow proteinuria related to polymyositis have rarely been reported. Herein, we report a case of a 41-year-old male who presented with edema of both lower extremities. Laboratory studies revealed elevated creatine phosphokinase level, hypoalbuminemia, and a moderate amount of proteinuria, although albuminuria was not dominant. Urine electrophoresis showed an abnormally restricted zone in the β-fraction, which suggested overflow proteinuria of non-glomerular origin. Despite intravenous hydration, his serum creatine phosphokinase level did not decrease and his symptoms did not improve. Electromyography showed myopathy, and muscle biopsy revealed findings consistent with polymyositis. After corticosteroid therapy, his creatine phosphokinase level and proteinuria decreased and his clinical symptoms improved. This case demonstrates an atypical presentation of polymyositis manifested by overflow proteinuria.

Background: Fabry disease is a rare X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency. With the advancement of molecular diagnostic tools, more disease-causing mutations in a-galactosidase A (GLA) have been identified in Fabry disease. We found a novel mutation in a Korean family with predominant renal manifestations of the disease. Case presentation: A 24-year-old man who wanted to donate a kidney to his 28-year-old brother with end-stage renal disease of unknown cause was evaluated. The 24-year-old man underwent percutaneous renal biopsy because of an accidentally found proteinuria. Electron microscopy of his renal biopsy showed numerous electron-dense multilamellar inclusions in the epithelial cytoplasm, typical for Fabry disease. Clinical and laboratory evaluation including the assessment of GLA enzyme activity and direct DNA sequencing in four members of the family were performed. Renal biopsy findings in the two affected male patients were described. Re-evaluation of a renal biopsy specimen of his 28-year-old brother obtained when he was diagnosed with renal failure revealed a very focal area of suspicious multilamellated structures in the Bowman's space. DNA sequencing on the young man, his brother, and his mother revealed a novel GLA gene mutation, c.263A > G (p.Tyr88Cys). The three all showed decreased alpha-galactosidase A activity. Conclusion: A novel GLA mutation, c.263A > G (p.Tyr88Cys), was found in a Korean family with predominant renal manifestations of Fabry disease.

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. 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

Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice.Methods. Histologic changes and expressions of transforming growth factor-β(TGF-β), collagen IV,fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG),3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice.Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine1177-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change.Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice.

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.

Background Renal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes. Methods Dapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks. We used voglibose, an alpha-glucosidase inhibitor, as a comparable counterpart to SGLT2 inhibitor because of its postprandial glucose-lowering effect without proven renoprotective effects. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10, each). Changes in blood glucose, urine albumin, creatinine clearance, and oxidative stress were measured. Inflammatory cell infiltration, mesangial widening, and interstitial fibrosis in the kidney were evaluated by histological analysis. The effects of dapagliflozin on renal expression of the RAS components were evaluated by quantitative RT-PCR in renal tissue. Results After treatment, hyperglycemia and urine microalbumin levels were attenuated in both OL-DA and OL-VO rather than in the OL-C group (P < 0.05). The urine angiotensin II (Ang II) and angiotensinogen levels were significantly decreased following treatment with dapagliflozin or voglibose, but suppression of urine Ang II level was more prominent in the OL-DA than the OL-VO group (P < 0.05). The expressions of angiotensin type 1 receptor and tissue oxidative stress markers were markedly increased in OL-C rats, which were reversed by dapagliflozin or voglibose (P < 0.05, both). Inflammatory cell infiltration, mesangial widening, interstitial fibrosis, and total collagen content were significantly increased in OL-C rats, which were attenuated in OL-DA group (P < 0.05). Conclusion Dapagliflozin treatment showed beneficial effects on diabetic nephropathy, which might be via suppression of renal RAS component expression, oxidative stress and interstitial fibrosis in OLETF rats. We suggest that, in addition to control of hyperglycemia, partial suppression of renal RAS with an SGLT2 inhibitor would be a promising strategy for the prevention of treatment of diabetic nephropathy.

Malnutrition is a major issue in patients with chronic kidney disease (CKD), adversely affecting morbidity, mortality, functional activity and patients’ quality of life. Our knowledge of the pathogenic mechanisms of malnutrition in patients with CKD, including endstage renal disease, has been improved. This has led to the development of clinical practice guidelines for nutritional care in CKD which provide a framework for the nutritional issues facing patients and physiccians. Extensive research in the field of nutrition in patients with CKD has resulted in the formation of general guidelines, although some uncertainties still exist on some of the best therapeutic or preventive options in uremic malnutrition. It is important to search actively for malnutrition since early diagnosis and treatment can improve the prognosis for CKD patients and reduce the monetary costs connected with treatment.

The response to erythropoietin (EPO) treatment varies considerably in individual patients on chronic hemodialysis. The EPO resistance index (ERI) has been considered useful to assess the EPO resistance and can be easily calculated in the clinic. The aim of this study was to investigate the association between ERI and left ventricular mass (LVM) and function and to determine whether ERI was associated with cardiovascular events in patients on hemodialysis. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on hemodialysis. The ERI was determined as the weekly weight-adjusted dose of EPO (U/kg/week) divided by hemoglobin concentration (g/dL). Patients were divided into three groups by tertiles of ERI. Patients with higher tertiles of ERI had a higher LVM index and lower LV ejection fraction compared with those with lower tertiles of ERI (P = 0.019 and P = 0.030, respectively). The median follow-up period was 53 months. The Kaplan-Meier plot showed increased frequency of cardiovascular events in patients with higher tertiles of ERI, compared with those with lower tertiles of ERI (P = 0.011, log-rank test). The multivariate Cox proportional hazard models showed that the ERI was the significant independent predictor of cardiovascular events (HR 3.00, 95% CI, 1.04-8.62, P = 0.042). Our data show that ERI was related with LVM index, LV systolic function and cardiovascular events in patients with hemodialysis. By monitoring of ERI, early identification of the EPO resistance may be helpful to predict the cardiovascular risk in hemodialysis patients.

Background. The peroxisome proliferator-activated receptor-a (PPARa) is a lipid-sensing transcriptional factor that has a role in gluco-oxidative stress and lipotoxicity. Forkhead box O (FoxO)s and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1a are also known to regulate cell metabolism, cell cycle arrest, apoptosis and oxidative stress during stressful conditions. We evaluated whether PPARa–FoxOs–PGC-1a signaling in overfed spontaneously hypertensive rats (SHR) has a protective role in the kidney. Methods. Male SHR and Wistar–Kyoto rats (WKY) fed a high-fat diet (HFD) received treatment with fenofibrate, PPARa agonist or tempol, antioxidants for 12 weeks and were evaluated about the PPARa–FoxOs–PGC-1a pathway. Results. The SHRs with an HFD had an elevated systolic pressure, plasma insulin, free fatty acid (FFA) and triglyceride (TGs) levels, and they had induced glucose intolerance as well as albuminuria, glomerular expansion and renal inflammation. An HFD caused the accumulation of intra-renal FFA and TGs and this was related to a decrease in the PPARa expression, the activation of phosphatidylinositol 3-kinase (PI3K)–Akt, phosphorylation of FoxO3a and decreases in the PGC-1a and estrogen-related receptor (ERR)-1a expressions, which suppressed the superoxide dismutase (SOD2) and Bcl-2 expressions and led to increases in oxidative stress and the number of apoptotic renal cells. Interestingly, administering fenofibrate or tempol to the HFD-induced SHRs reversed all of the renal phenotypes by increasing the PPARa expression with concomitant inactivation of the PI3K–Akt pathway, dephosphorylation of FoxO3a and activation of PGC-1a–ERR-1a signaling, and this all resulted in ameliorating the oxidative stress and apoptotic cell death. Conclusion. Our results demonstrated that PPARa agonists or antioxidants are associated with improvement of the circulating FFA and TGs levels and this prevents HFDinduced renal lipotoxicity and hypertension by the activation of PPARa and its downstream signals of both FoxO3a and PGC-1a.