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The prevalence of chronic kidney disease (CKD) is steadily increasing, and it is a global health burden. Exercise has been suggested to improve physical activity and the quality of life in patients with CKD, eventually reducing mortality. This study investigated the change in physical performance after exercise in dialysis-dependent patients with CKD and analyzed differentially expressed proteins before and after the exercise. Plasma samples were collected at enrollment and after 3 months of exercise. Liquid chromatography with tandem mass spectrometry analysis and data-independent acquisition results were analyzed to determine the significantly regulated proteins. A total of 37 patients on dialysis were recruited, and 16 were randomized to exercise for 3 months. The hand grip strength and the walking speed significantly improved in the exercise group. Proteome analysis revealed 60 significantly expressed proteins after 3 months of exercise. In the protein functional analysis, the significantly expressed proteins were involved in the immune response. Also, some of the key significantly expressed proteins [(M Matrix metallopeptidase 9 (MMP-9), Activin A Receptor Type 1B (ACVR1B), Fetuin B (FETUB)] were validated via an enzyme-linked immunosorbent assay. Our results showed that exercise in dialysis-dependent patients with CKD could improve their physical performance. These results indicated that this beneficial effect of exercise in these populations could be associated with immune response.

Background: Cell-free mitochondrial DNA (cf-mtDNA) has recently been in the spotlight as an endogenously produced danger molecule that can potentially elicit inflammation. However, its clinical and prognostic implications are uncertain in patients undergoing hemodialysis. Methods: We examined the association of baseline cf-mtDNA categorized as tertiles with health-related quality of life (HRQOL), inflammatory cytokines, and mortality in a multicenter prospective cohort of 334 patients on hemodialysis. To better understand cf-mtDNA-mediated inflammation, we measured cytokine production after in vitro stimulation of bone marrow-derived macrophages (BMDMs) with mtDNA. Results: The higher cf-mtDNA tertile had a longer dialysis vintage, a greater comorbidity burden, and increased levels of inflammatory markers, including high-sensitivity-C-reactive protein, tumor necrosis factor-alpha, CXCL16, and osteoprotegerin. In particular, mtDNA augmented inflammatory cytokine release from BMDMs by lipopolysaccharide, the levels of which are reported to be increased in hemodialysis patients. Although the patients with higher levels of cf-mtDNA generally had lower (poorer) scores for HRQOL, cf-mtDNA was not associated with all-cause mortality in hemodialysis patients. Conclusion: cf-mtDNA was correlated with poor clinical status and modestly associated with impaired quality of life in patients on hemodialysis. In proinflammatory milieu in end-stage renal disease, these associations may be attributed to the boosting effects of cf-mtDNA on inflammation.

Background Elevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients. Methods This prospective, multicenter, open-label study enrolled patients with CKD stages 3–5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA. Results A total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = − 0.406, P P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P P Conclusions OSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported. Trial registration Clinical Research Information Service (KCT0001875. 14 December 2015.)

Background : : Online hemodiafiltration (OL-HDF) offers considerable advantages in clearance of molecules of various sizes. However, evidence of clinical effects of OL-HDF is scarce in Korea. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. Methods : : Adult patients with end-stage renal disease undergoing hemodialysis (HD) were prospectively enrolled in a K-cohort (CRIS no. KCT0003281) from 6 tertiary hospitals in South Korea. We recruited 435 patients, 339 of whom were on HD at enrollment. One hundred eighty-two patients were followed for more than 24 months. Among them, 44 were switched to OL-HDF for more than 12 months without conversion to HD. We used a paired t test to compare baseline and 24-month follow-up results. Results : : The mean age of the subjects was 61.2 ± 12.2 years, and 62.6% were male. The baseline hemoglobin level was not significantly different between HD and OL-HDF group (10.61 ± 1.15 vs. 10.46 ± 1.03 g/dL, P = 0.437). However, the baseline serum protein and albumin levels were significantly lower in the OL-HDF group (6.82 ± 0.49 vs. 6.59 ± 0.48 g/dL, P = 0.006; 3.93 ± 0.28 vs. 3.73 ± 0.29 g/dL, P < 0.001). In patients switched to OL-HDF, levels of hemoglobin and serum albumin significantly increased (10.46 ± 1.03 vs. 11.08 ± 0.82 g/dL, P = 0.001; 3.73 ± 0.29 vs. 3.87 ± 0.30 g/dL, P = 0.001). The normalized protein catabolic rate decreased after 24 months, but the change was not significant (1.07 ± 0.25 vs. 1.03 ± 0.21 g/kg/day, P = 0.433). Although the dose of erythropoiesis-stimulating agent was lower in patients who converted to HDF, it was not significantly different (-115.7 ± 189.7 vs. -170.5 ± 257.1 P = 0.206). Conclusion : : OL-HDF treatment over more than 12 months was associated with no harmful effects on anemia and nutritional status.

Background: Hemodialysis patients with chronic kidney disease exhibit impaired exercise tolerance and functional decline. Despite the life-saving benefits of adequate dialysis, those declines translate into frailty and deteriorating quality of life (QoL). This study evaluated the effects of an intradialytic aerobic exercise program on frailty, dialysis adequacy, and QoL among hemodialysis patients. Methods: Patients at an university hospital-affiliated hemodialysis center were randomly assigned to an exercise group (n = 18) or a control group (n = 21). The 12-week aerobic exercise program comprised 40 to 70 minutes of ergometer cycling 3 times/wk and a single education session. The control group completed only the education session. Outcomes were assessed at the time of enrollment, week 4, week 8, and week 12 using Fried’s frailty phenotype measures (gait speed, grip strength, vitality, body mass index, and physical activity), the short physical performance battery (SPPB), Kt/V urea, and the Short Form-36 questionnaire. Results: There were significant interactions between groups and follow-up times in the frailty score (p < 0.001), gait speed (p < 0.001), SPPB (p < 0.001), and mental QoL (p = 0.03). The intention-to-treat and per-protocol analyses revealed that the exercise group exhibited significant improvements in frailty score (p < 0.001), gait speed (p < 0.001), grip strength (p < 0.001), exhaustion (p = 0.02), SPPB (p = 0.01), dialysis adequacy (p = 0.01), and physical QoL (p = 0.003). Conclusion: An intradialytic aerobic exercise program could be a safe, feasible, and appropriate additional strategy to routine care among hemodialysis patients for improvements in frailty, dialysis adequacy, and QoL.

BackgroundInterstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis.MethodsSeventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes.ResultsPatients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P ConclusionsUrinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

We examined the effects of empagliflozin, a selective inhibitor of Na+-glucose cotransporter 2, on mitochondrial quality control and autophagy in renal tubular cells in a diabetic environment in vivo and in vitro. Human renal proximal tubular cells (hRPTCs) were incubated under high-glucose conditions. Diabetes was induced with streptozotocin in male C57BL/6J mice. Improvements in mitochondrial biogenesis and balanced fusion-fission protein expression were noted in hRPTCs after treatment with empagliflozin in high-glucose media. Empagliflozin also increased autophagic activities in renal tubular cells in the high-glucose environment, which was accompanied with mammalian target of rapamycin inhibition. Moreover, reduced mitochondrial reactive oxygen species production and decreased apoptotic and fibrotic protein expression were observed in hRPTCs after treatment with empagliflozin, even in the hyperglycemic circumstance. Importantly, empagliflozin restored AMP-activated protein kinase-α phosphorylation and normalized levels of AMP-to-ATP ratios in hRPTCs subjected to a high-glucose environment, which suggests the way that empagliflozin is involved in mitochondrial quality control. Empagliflozin effectively suppressed Na+-glucose cotransporter 2 expression and ameliorated renal morphological changes in the kidneys of streptozotocin-induced diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased and 8-hydroxy-2′-deoxyguanosine content was low in renal tubular cells of empagliflozin treatment groups compared with those of the diabetic control group. We suggest one mechanism related to the renoprotective actions of empagliflozin, which reverse mitochondrial dynamics and autophagy.

Background and Aims Low physical performance in patients undergoing maintenance hemodialysis is associated with a high mortality rate. We investigated the clinical relevance of gait speed and handgrip strength, the two most commonly used methods to assess physical performance. Method We obtained data regarding gait speed and handgrip strength from 277 hemodialysis patients and evaluated their relationship with baseline parameters, mental health, plasma inflammatory markers, and major adverse clinical outcomes. Low physical performance was defined by the recommendations suggested by the Asian Working Group on Sarcopenia. Results The prevalence of low gait speed and handgrip strength were 28.2% and 44.8%, respectively. Old age, low serum albumin levels, high comorbidity index, and impaired cognitive functions were associated with low physical performance. Patients with isolated low gait speed exhibited a general trend for worse quality of life than those with isolated low handgrip strength. Gait speed and handgrip strength showed very weak correlations with had different determinant factors (older age, the presence of diabetes, and lower serum albumin for low gait speed, and lower body mass index, and the presence of previous cardiovascular events for low handgrip strength). Patients with low gait speed and handgrip strength had elevated levels of plasma endocan and matrix metalloproteinase-7 and the highest risk of all-cause mortality and cardiovascular events among the groups (adjusted hazard ratio of 2.72, p = 0.024). Conclusion Gait speed and handgrip strength reflected distinctive aspects of patient characteristics and that their combination improved the prediction of adverse clinical outcomes in hemodialysis patients. Gait speed seems to be a better indicator for poor patient outcomes compared with handgrip strength.

Background and Aims The global prevalence and incidence of maintenance dialysis are increasing. Among the modalities of RRT, maintenance hemodialysis (HD) has been a major method worldwide for patients with end-stage renal disease (ESRD). The recent introduction of online-hemodiafiltration (OL-HDF) may offer major advantages in clearing molecules of various sizes, reducing HD-associated amyloidosis and chronic inflammation. Because this modality has been officially approved for ESRD patients, the number of patients worldwide undergoing OL-HDF therapy have consistently increased. However, evidence of clinical effects of OL-HDF is scarce. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. Method The present study included data from a K-cohort (CRIS no. KCT0003281) of prospectively enrolled adult patients with ESRD undergoing hemodialysis in 6 tertiary hospitals in South Korea. A total of 435 patients was recruited, and 339 patients were on HD at the beginning of the study period. Among the 339 patients, 182 were followed up for more than 24 months. During the follow-up period, 135 patients remained on HD and 47 switched to HDF. However, 3 of the 47 who switched to HDF later returned to HD. We compared clinical parameters in 44 patients who switched to OL-HDF and 135 patients who remained on HD (Figure 1). We used a paired t-test to compare baseline and 24-month follow-up results. Results The mean age of the study subjects was 61.2 ± 12.2 years, and 62.6% were male. The duration of dialysis was 2.9 ± 4.4 months. In the group that was switched from HD to OL-HDF, the levels of Hgb and serum albumin increased significantly (10.46 ± 1.03 vs. 11.08 ± 0.82, P = 0.001, and 3.73 ± 0.29 vs. 3.87 ± 0.30, P = 0.001, respectively). Although the normalized protein catabolic rate (nPCR) decreased from baseline after 24 months, the change was not significant (1.07 ± 0.25 vs. 1.03 ± 0.21, P = 0.433). Calcium and calcium-phosphorus products also increased significantly after OL-HDF therapy (8.32 ± 0.75 vs. 8.75 ± 0.80, P < 0.001 and 41.89 ± 12.62 vs. 50.80 ± 20.79, P = 0.013, respectively). To determine possible confounding effects of clinical factors, we conducted a linear regression analysis with multiple adjustments for changes in various laboratory values after HDF conversion. Conversion to HDF resulted in elevation of serum calcium and albumin levels, both of which were significant even after adjustment for baseline demographics, inflammation, and dialysis duration. Conclusion In conclusion, long-term OL-HDF treatment over 12 months or longer was associated with no detrimental effects on anemia or nutritional status. To investigate the effects of OL-HDF therapy, evaluating more parameters over a longer follow-up period with a larger number of patients is needed. Figure 1.

Background Oxidative stress induced by chronic hyperglycemia is recognized as a significant mechanistic contributor to the development of diabetic kidney disease (DKD). Nonphagocytic nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in many cell types and in the kidney tissue of diabetic animals. We designed this study to explore the therapeutic potential of chloroquine (CQ) and amodiaquine (AQ) for inhibiting mitochondrial Nox4 and diabetic tubular injury. Methods Human renal proximal tubular epithelial cells (hRPTCs) were cultured in high-glucose media (30 mM D-glucose), and diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57BL/6J mice. CQ and AQ were administered to the mice via intraperitoneal injection for 14 weeks. Results CQ and AQ inhibited mitochondrial Nox4 and increased mitochondrial mass in hRPTCs under high-glucose conditions. Reduced mitochondrial ROS production after treatment with the drugs resulted in decreased endoplasmic reticulum (ER) stress, suppressed inflammatory protein expression and reduced cell apoptosis in hRPTCs under high-glucose conditions. Notably, CQ and AQ treatment diminished Nox4 activation and ER stress in the kidneys of STZ-induced diabetic mice. In addition, we observed attenuated inflammatory protein expression and albuminuria in STZ-induced diabetic mice after CQ and AQ treatment. Conclusion We substantiated the protective actions of CQ and AQ in diabetic tubulopathy associated with reduced mitochondrial Nox4 activation and ER stress alleviation. Further studies exploring the roles of mitochondrial Nox4 in the pathogenesis of DKD could suggest new therapeutic targets for patients with DKD., Graphical Abstract

In this paper, the vibration characteristic of elevator rope was verified. To this end, the dynamic model of elevator rope was derived using Rayleigh-Ritz method. And the numerical simulation was carried out for theoretical predictions. To calculate the response of elevator rope, the parameters of real elevator was considered. Based on numerical simulation, the vibration experiments were carried out to validate the dynamic model of elevator rope. To measure the vibration of elevator rope, the CCD camera and the line laser was considered. And the image processing technique was applied to calculate the horizontal displacement of elevator rope. Measurement equipment was installed in elevator shaft at 3 m, 29 m, and 51 m from the base level. Shaker was equipped at the bottom of elevator rope to excite the rope. In experiments, the displacement of rope was measured when the elevator rope was subjected to each natural frequencies. Experimental results are in good agreement with theoretical predictions.

Background: Hyperuricemia is common in end-stage renal disease (ESRD) patients, and many previous studies have reported the associations between hyperuricemia and adverse cardiovascular outcomes, which are the major cause of death in such patients. We investigated the relationship between serum uric acid level and the severity of coronary stenosis in ESRD patients on maintenance hemodialysis (MHD). Methods: Among 721 patients who started MHD treatment, 102 underwent coronary angiographic tests complaining of chest discomfort that was new at initiation of MHD. We collected data on uric acid level and coronary artery luminal diameter, defining luminal diameter narrowing of more than 50% in any major coronary artery as critical-stenosis. Results: We detected critical coronary artery stenosis in 52 (57.8%) patients. The mean uric acid level was 6.6 ± 2.2 mg/dL, and that was significantly higher in the critical-stenosis group (4.9 ± 1.4 mg/dL vs. 7.8 ± 2.0 mg/dL, P < 0.001). The only independent predictor of critical-stenosis in multivariate analysis was serum uric acid level (P < 0.001). Conclusion: High serum uric acid was associated with severe coronary artery stenosis in Korean ESRD patients. Hyperuricemia is a readily modifiable factor, and appropriately preventing it could provide significant benefits in ESRD patients.

This study is concerned with the theoretical modelling and experimental verification of the coupled vibrations of building and elevator ropes. The elevator ropes consist of a main rope which supports the cage and the compensation rope which is connected to the compensation sheave. The elevator rope is a flexible wire with a low damping, so it is prone to vibrations. In the case of a high-rise building, the rope length also increases significantly, so that the fundamental frequency of the elevator rope approaches the fundamental frequency of the building thus increasing the possibility of resonance. In this study, the dynamic model for the analysis of coupled vibrations of building and elevator ropes was derived by using Hamilton's principle, where the cage motion was also considered. An experimental testbed was built to validate the proposed dynamic model. It was found that the experimental results are in good agreement with the theoretical predictions thus validating the proposed dynamic model. The proposed model was then used to predict the vibrations of real building and elevator ropes.

Introduction: Identification of the risk factors and treatment of the decrease in muscle mass or strength are important to improve the prognosis of patients undergoing hemodialysis (HD). Previous studies have investigated the association between vitamin D level and muscle mass or strength in patients undergoing HD. However, there are conflicting results regarding this association. Objective: To evaluate the association between vitamin D level and muscle mass indices, strength, or physical performance in patients undergoing HD. Methods: This study was performed in a tertiary medical center. We included patients undergoing HD aged ≥20 years. A total of 84 patients were enrolled. The patients were divided into tertiles based on the 25-hydroxy (25-OH) vitamin D level as follows: lowest tertile (Lowest T, n = 28), middle tertile (Middle T, n = 28), and highest tertile (Highest T, n = 28). We evaluated the association between the tertiles and clinical outcomes including nutritional status, muscle mass, muscle function, handgrip strength (HGS), physical performance, and health-related quality of life (HRQoL) scales. Results: There were no significant differences in the muscle mass indices and nutritional markers according to tertiles of 25-OH vitamin D level. However, 25-OH vitamin D level as a continuous variable or the tertile of 25-OH vitamin D level as a categorical variable was positively associated with HGS. Logistic and linear regression analyses showed a consistent superiority of the Highest T in HGS compared with the Lowest or Middle T. Although the statistical significance was weak, the scores of various physical performance tests and the HRQoL scales were highest in the Highest T among the 3 tertiles. Conclusion: The present study demonstrated that serum vitamin D level is associated with HGS in patients undergoing HD regardless of muscle mass indices or nutritional status.

Background Graft biopsy is the gold standard for the differential diagnosis of graft dysfunction. The time interval between transplant surgery and biopsy often provides clinicians with diagnostic clues. However, the clinicopathologic features of late graft biopsy, especially those obtained at more than 5 years after kidney transplant, are not well understood. Materials and Methods We retrospectively collected graft biopsy tissues obtained from kidney transplant recipients who underwent indication biopsy between February 2012 and March 2017. Patients were divided according to their post-transplant period, and their clinical characteristics, pathologic diagnosis, and Banff scores were compared across groups. Results A total of 410 indication biopsy specimens obtained from 321 kidney transplant recipients were analyzed in this study. Overall, the incidence of T cell–mediated rejection, borderline rejection, and BK virus–associated nephropathy decreased while that of antibody-mediated rejection, nonspecific interstitial fibrosis and tubular atrophy, and glomerulonephritis increased over time. Most samples obtained over 5 years after kidney transplant exhibited chronic glomerular and tubulointerstitial injuries irrespective of their pathologic diagnosis. In patients whose post-transplant period was less than 5 years, urine protein-to-creatinine ratio was significantly elevated in the glomerulonephritis and chronic active antibody-mediated rejection groups only. In contrast, patients who underwent graft biopsy more than 5 years after kidney transplant showed significantly high levels of proteinuria irrespective of the pathologic diagnosis, and there was no statistical difference between groups. Conclusion We demonstrated that the etiology of graft dysfunction is largely influenced by the biopsy time point.

BackgroundPatients with chronic kidney disease (CKD) experience much more marked and earlier muscle wasting than subjects who do not have chronic illnesses. However, a few studies that have examined sarcopenia have been reported in CKD patients. We investigated the prevalence of sarcopenia in predialysis and dialysis outpatients with CKD and explored its relationship with the clinical outcomes.MeasurementsSarcopenia was defined as reduced muscle strength accompanied by decreased adjusted appendicular skeletal muscle (ASM), while those patients who exhibited only one of these characteristics were categorized as presarcopenic patients. ASM was measured by bioimpedence analysis, and muscle strength was evaluated by handgrips. ASM was adjusted by weight (ASM/wt). Patients were prospectively followed for up to 2 years.ResultsOne hundred seventy-nine patients were recruited (114 male and 65 female patients who were classified into 103 predialysis patients and 76 dialysis patients, with 44.7% having diabetes). Their mean age was 60.6 ± 13.5 years old. The prevalence of sarcopenia was 9.5%, while 55.9% of the patients were categorized as presarcopenic. The ASM/wt index showed significant correlations with age, handgrip strength, HOMA-IR and frailty scores. Multivariate Cox proportional hazards models demonstrated that the risk of hospitalization was significantly higher for patients with presarcopenia [hazard ratio (HR), 2.48; 95% confidence interval (CI), 1.180–5.230], and the risk of hospitalization was much higher for patients with sarcopenia than for patients in the nonsarcopenic group (HR, 9.11; 95% CI, 2.295–25.182)ConclusionsSarcopenia and presarcopenia, which were defined using the ASM/wt index and handgrip strength, predicted a poorer, hospitalization-free survival in CKD patients

Background: Vitamin D has pleiotropic effects important for the proper functioning of multiple organ systems. We investigated whether serum 25-hydroxyvitamin D [25(OH)D] levels influenced hospitalization-free survival in patients with chronic kidney disease (CKD). Methods: In this prospective study, serum levels of 25(OH)D were measured in 210 patients with CKD in the winter of 2009. Data regarding hospitalizations were collected over the subsequent 3 years. Results: Vitamin D deficiency, as defined by a serum 25(OH)D level below 15 ng/mL, was observed in 76.7% of the patients. The mean 25(OH)D serum level was 13.6 ± 7.8 ng/mL in predialysis patients (n = 62) and 11.3 ± 6.7 ng/mL in dialysis patients (n = 148). During the follow-up, 107 patients (28 predialysis and 79 dialysis) were hospitalized because of infectious (33.6%) or cardiovascular diseases (23.4%). Predialysis and dialysis groups were divided into 2 subgroups based on the median 25(OH)D serum level. Kaplan–Meier analysis revealed that the risk of hospitalization was significantly lower in both predialysis and dialysis patients with above-median serum 25(OH)D levels (log-rank test; P = 0.043 and 0.002, respectively). Multivariate Cox proportional hazards models also demonstrated that the risk of hospitalization was significantly lower for patients with higher serum 25(OH)D levels in both the predialysis (hazard ratio, 0.963; 95% confidence interval, 0.93–0.99) and dialysis groups (hazard ratio, 0.955; 95% confidence interval, 0.91–0.99). Conclusion: A lower serum 25(OH)D level predicted poorer hospitalization-free survival in both predialysis and dialysis CKD patients.

Background/Aims: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. Methods: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. Results: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was −41.3% ± 26.1% (p < 0.001) in the regular-dose group and −21.1% ± 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. Conclusions: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

Non-traumatic exertional rhabdomyolysis (exRML) occurs in individuals with normal muscles when the energy supplied to the muscle is insufficient. Here, we report 11 cases of spinning-induced rhabdomyolysis and review related literature. Spinning is a kind of indoor bicycle sport. The 11 patients who were diagnosed with exRML and admitted to CHA Bundang Medical Center were female and their ages ranged from 15 to 46 years. Two to three days prior to the presentation, the patients had attended a spinning class for the first time. All the patients had been otherwise healthy without any known medical illnesses. They were successfully treated without any complications, except mild non-symptomatic hypocalcemia. However, in the literature, severe complications such as compartment syndrome or acute kidney injury had been reported in relation to exRML including spinning-induced rhabdomyolysis. This spinning exercise needs prior guidelines and specific warnings to prevent exertional rhabdomyolysis.

The cardiovascular diseases are the leading cause of mortality in end-stage renal disease (ESRD) patients. However, roles of statins are still controversial in dialysis-dependent ESRD patients regardless of having proven coronary artery occlusive disease. The aim of this study was to examine the benefit of statin following percutaneous coronary intervention (PCI) in ESRD patients who have proven coronary artery occlusive disease. This study was based on the National Health Insurance Service-National Sample Cohort in South Korea. We included 150 ESRD patients on chronic hemodialysis who underwent PCI with stenting between 2002 and 2013. The primary outcome was a composite of myocardial infarction, stroke, and all-cause mortality. Multivariate time-dependent Cox regression analysis were performed, and statin therapy after PCI was treated as a time-dependent variable. During 3.15 ± 2.71 (mean ± standard deviation) years of follow-up, there were 82 patients with primary outcome. The adjusted hazard ratio for statin use was 0.54 [0.33–0.90] compared to no statin use. This study showed that statin has significant benefit on reducing adverse events risk in dialysis-dependent ESRD patients after PCI.

We investigated the effects of chloroquine (CQ) and amodiaquine (AQ) on AMPK phosphorylation in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether CQ- or AQ-mediated AMPK activity restoration attenuated diabetic tubulopathy by normalizing mitochondrial fragmentation. Human renal proximal epithelial cells (HKC8) were incubated in high-glucose conditions. Diabetes was induced with streptozotocin in male C57/BL6J mice. Treatment with CQ or AQ abolished high-glucose-induced phospho-AMPK and phosph-PGC1α down-regulation in HKC8 cells. Improvements in functional mitochondrial mass and balanced fusion/fission protein expression were observed in HKC8 cells after treatment with CQ or AQ in high-glucose conditions. Moreover, decreased mitochondrial ROS production and reduced apoptotic and fibrotic protein expression were noted in HKC8 cells after treatment with CQ or AQ, even in high-glucose conditions. CQ and AQ treatment effectively mitigated albuminuria and renal histopathologic changes and increased AMPK activity in the kidneys of diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased, and 8-OHdG content was low in the renal tubular cells of the CQ and AQ treatment groups compared with those of the diabetic control group. Our results suggest that CQ and AQ may be useful treatments for patients with diabetic kidney disease.

This study is concerned with the theory and application of a tuneable dynamic absorber. The dynamic characteristics of the tuneable dynamic absorber are discussed in terms of the mass ratio, natural frequency of the main structure, natural frequency of a dynamic absorber and excitation frequency. We proposed a semi-active dynamic absorber with a natural frequency that can change through the use of repulsive forces produced by permanent magnets and electromagnetic forces induced by current flowing through a coil. A simple active control algorithm is implemented in the LabView software and the experimental results showed that when the proposed semi-active dynamic absorber is used with the active control algorithm, the vibrations of a structure can be more effectively suppressed than when a passive dynamic absorber with a fixed natural frequency is used.

The active vibration control of a rectangular plate either partially or fully submerged in a fluid was investigated. Piezoelectric sensors and actuators were bonded to the plate, and the assumed mode method was used to derive a dynamic model for the submerged plate. The properties of the piezoelectric actuators and sensors, as well as their coupling to the structure, were used to derive the corresponding equations of their behaviour. The fluid effect was modelled according to the added virtual mass obtained by solving the Laplace equation. The natural vibration characteristics of the plate both in air and in water were obtained theoretically and were found to be consistent with the experimental results, and the changes in the natural frequencies resulting from submersion in fluid can be accurately predicted. A multi-input, multi-output positive position feedback controller was designed by taking the natural vibration characteristics into account and was then implemented by using a digital controller. The experimental results show that piezoelectric sensors and actuators along with the control algorithm can effectively suppress the vibration of a rectangular plate both in air and submerged in a fluid.

Background: Recent evidence demonstrates that high doses of epoetin-alpha (EPO-α) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-α compared with darbepoetin-alpha (DA-α) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-α is as effective as DA-α for anemia in chronic kidney disease (CKD) patients not receiving dialysis. Methods: Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-α (10,000 unit) or DA-α (50 μg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-α and DA-α treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. Results: The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. Conclusion: Biweekly high doses of EPO-α therapy may be equally as effective as Q2W DA-α therapy in maintaining target Hb levels in non-dialysis CKD patients.

Supplemental Digital Content is available in the text, Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria. We enrolled 220 cases of type 2 diabetic patients who underwent renal biopsy. They were grouped according to the presence of nephritic-range proteinuria and pathological features. Baseline characteristics, laboratory findings, types of pathological diagnosis, and renal outcomes were analyzed in patients with heavy proteinuria. Upon kidney biopsy, 129 patients (58.6%) showed nephritic-range proteinuria. Patients with heavy proteinuria (an average urine protein-to-creatinine ratio of 10,008 ± 7307 mg/gCr) showed lower serum albumin levels and higher total cholesterol levels, but did not show any difference in age, duration of diabetes, renal function, or the presence of retinopathy compared with those with mild-to-moderate proteinuria (an average urine protein-to-creatinine ratio of 1581 ± 979 mg/gCr). Renal biopsy revealed that the prevalence of NDRD was 37.2% in patients with heavy proteinuria, which was significantly lower than that in patients with mild-to-moderate proteinuria (63.7%). The most common pathological types of NDRD were membranous nephropathy (41.7%), IgA nephropathy (14.6%), and minimal change disease (10.4%). NDRD patients showed lower prevalence of diabetic retinopathy and better kidney function irrespective of proteinuria. Immunosuppressive treatment was administered more frequently in patients with heavy proteinuria (56.3%) compared with patients with mild-to-moderate proteinuria (20%) because of the pathological differences according to the amount of proteinuria. Renal outcomes were significantly worse in patients with DN than in patients with NDRD. DN patients with heavy proteinuria exhibited different prevalence of NDRD and worse prognosis. Renal biopsy in type 2 diabetic patients should be more extensively considered to accurately diagnose NDRD, guide further management, and predict renal outcomes, especially in patients with nephrotic-range proteinuria.

Purpose.In this study, we investigated the effect of PGC1αactivators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1αattenuates diabetic tubulopathy by normalizing mitochondrial homeostasis.Methods. HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice. AICAR or metformin was used as a PGC1αactivator.Results.Treatment with the PGC1αactivators AICAR and metformin improved functional mitochondrial mass in HKC8 cells in high-glucose conditions. Moreover, in renal proximal tubular cells, increased PGC1αactivity correlated with the reversal of changes in Drp1, Mfn1, and LC3-II protein expression in a high-glucose environment. Normalized mitochondrial life cycles resulted in low ROS production and reduced apoptosis. AICAR and metformin treatment effectively mitigated albuminuria and renal histopathology and decreased the expression of TGFβ1 andαSMA in the kidneys of diabetic mice.Conclusions. Our results demonstrate that increases in PGC1αactivity improve diabetic tubulopathy by modulating mitochondrial dynamics and autophagy.

The active lateral suspension (ALS) of a train consists of either active or semi-active technologies. However, such an active system on a real railway vehicle is not easy to test because of cost and time. In this study, a hardware-in-the-loop simulation (HILS) system is developed to test the ALS. To this end, the dynamic model of a railway vehicle is equipped with the actuator, two bogies and four-wheel sets, and the ALS is used. The proposed HILS system consists of an alternating current servo motor connected to a ball-screw mechanism and a digital control system. The digital control system implements the dynamic model and the control algorithm. The design and manufacture of the HILS system are explained in detail. Both the passive damper and the magneto-rheological (MR) fluid damper are tested using the HILS system, where the sky-hook control algorithm was applied for the MR fluid damper. Experimental results show that the proposed HILS system can be effectively used for the performance estimation of the ALS.

This paper is concerned with the suppression of vibrations and radiated sound of a ring-stiffened circular cylindrical shell in contact with unbounded external fluid by means of piezoelectric sensors and actuators. The dynamic model of a circular cylindrical shell based on the Sanders shell theory was considered together with a ring stiffener model. The mass and stiffness matrices for a ring stiffener were newly derived in this study and added to the mass and stiffness matrices of the cylindrical shell, respectively. The fluid-added mass matrix, which was derived by using the baffled shell theory, was also added to the mass matrix. Finally, the equations representing the piezoelectric sensor measurement and piezoelectric actuation complete the theoretical model for the addressed problem. The natural vibration characteristics of the ring-stiffened cylindrical shell both in air and in water were investigated both theoretically and experimentally. The theoretical predictions were in good agreement with the experimental results. An active vibration controller which can cope with a harmonic disturbance was designed by considering the modified higher harmonic control, which is, in fact, a band rejection filter. An active vibration control experiment on the submerged cylindrical shell was carried out in a water tank and the digital control system was used. The experimental results showed that both vibrations and radiation sound of the submerged cylindrical shell were suppressed by a pair of piezoelectric sensor and actuator.

The free flexural vibration of a cantilever plate partially submerged in a fluid is investigated. The fluid is assumed to be inviscid and irrotational. The virtual mass matrix is derived by solving the boundary-value problem related to the fluid motion using elliptical coordinates. The introduction of the elliptical coordinates naturally leads to the use of the Mathieu function. Hence, the virtual mass matrix which reflects the effect of the fluid on the natural vibration characteristics is expressed in analytical form in terms of the Mathieu functions. The virtual mass matrix is then combined with the dynamic model of a thin rectangular plate obtained by using the Rayleigh–Ritz method. This combination is used to analyze the natural vibration characteristics of a partially submerged cantilever plate qualitatively. Also, the non-dimensionalized added virtual mass incremental factors for a partially submerged cantilever plate are presented to facilitate the easy estimation of natural frequencies of a partially submerged cantilever plate. It is found that the numerical results are in good agreement with the previous results, thus validating the proposed approach.

In dealing with the dynamics of a flexible body, the rigid-body motions and elastic vibrations are analyzed separately. However, rigidbody motions cause vibrations, and elastic vibrations affect rigid-body motions, indicating the inherent coupling between rigid-body motions and elastic vibrations. The coupled equations of motion for a flexible body can be derived by means of Lagrange’s equations in terms of quasi-coordinates. The resulting equations of motion are hybrid and nonlinear. This paper proposes a unified approach for the equations of motion for a flexible body based on the perturbation method and the Lagrange’s equations of motion in terms of quasicoordinates and Euler parameters to analyze a more general case maneuvering. The resulting equations consist of zero-order nonlinear equations of motion which depict rigid-body motions and first-order time-varying linear equations of motion which depict perturbed rigid-body motions and elastic vibration. Hence, the input-shaped maneuvering can be applied to the zero-order equation considering the induced vibrations. Since the input-shaped maneuvering alone cannot achieve vibration suppression, the vibration suppression controller combined with the input-shaped maneuvering is proposed in this study. As a numerical example, a hub with elastic appendages is considered. Numerical results show that the unified modeling approach proposed in this paper is effective in numerical simulation and control design.

PURPOSE Investigating the risk of vascular access failure is critical for maintenance hemodialysis (MHD) patients. Erythropoietin stimulating agents (ESA) typically used for anemia of chronic kidney disease (CKD) may also stimulate neointimal hyperplasia, which is the most important factor in late arteriovenous fistula (AVF) failure. The aim of this study was to investigate whether ESA treatment is associated with late AVF failure. MATERIALS AND METHODS The late AVF failure group comprised 51 patients who underwent percutaneous intervention or surgery for fistula revision after successful use for at least three months. There were 51 controls whose AVF had been patent for at least 24 months. RESULTS The mean time from the first cannulation to late loss of AVF patency was 8.4±4.2 months. The average weekly dose of ESA was significantly higher in patients with AVF failure (4782.2±2360.5 IU/mL/wk vs. 7161.8±2775.2 IU/mL/wk, p

To investigate the clinical implications of frailty in chronic kidney disease patients undergoing maintenance hemodialysis and chronic peritoneal dialysis.In this prospective study, all of the participants completed the Short Form of the Kidney Disease Quality of Life questionnaire, Korean version, to determine their frailty phenotype. We also obtained blood chemistry and demographic data at enrollment. Data regarding the history of hospitalization and death were collected during the follow-up period.We recruited 1,658 patients (1,255 maintenance hemodialysis and 403 chronic peritoneal dialysis) from multidialysis units (n = 27). We excluded patients who had been hospitalized in the previous 3 months.Hospitalization and survival rate during study period.The participants' mean age was 55.2 ± 11.9 years old, and 55.2% were male. Among the participants, 34.8% were rated as frail and 45.7% as prefrail. Multivariate analysis demonstrated significant associations of frailty with age, comorbidity, disability, unemployment, higher body mass index, and a lower educational level. During the follow-up period (median 17.1 months), 608 patients (79 not frail, 250 prefrail, and 279 frail) were hospitalized, and 87 patients (10 not frail, 24 prefrail, and 53 frail) died (P .001). Frailty was associated with hospitalization (adjusted hazard ratio, 1.80; 95% confidence interval: 1.38-2.36) and mortality (hazard ratio, 2.37, 95% confidence interval: 1.11-5.02).The frailty phenotype was common even in, prevalent end-stage renal disease patients on dialysis, and was significantly associated with higher rates of hospitalization and mortality.

This paper is concerned with the dynamic modeling for the hardware-in-the-loop simulation of lateral vibrations of a railway vehicle. The resulting dynamic model is a nine degree-of-freedom model which can describe the lateral, roll and yaw motions of the car body and two bogies. It is assumed that the external disturbances come from wheel motions. In order to test the efficacy of the model, the linear quadratic regulator and the sky-hook control algorithm were designed and applied to the model. The simulation results show that both control algorithms are effective in suppressing the vibrations of railway vehicles.