Muscle ultrasound to diagnose sarcopenia in chronic kidney disease: a systematic review and bayesian bivariate meta-analysis.

OBJECTIVE: The aim of this systematic review was to assess the diagnostic test accuracy of muscle ultrasound for sarcopenia among chronic kidney disease (CKD) populations. BACKGROUND: Sarcopenia has become a worldwide health issue, especially for CKD patients. Conventional techniques of muscle mass assessment often prove limited, thus prompts increasing interest in ultrasound suitability. METHODS: We searched the Cochrane Library, PubMed and Embase for literature published up to June 2023. Ultrasound diagnosis of sarcopenia in CKD patients was included. Two independent investigators used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted valuable information from eligible studies. Using a Bayesian bivariate model, we pooled sensitivity and specificity values and summary receiver operating characteristic (SROC) curves. RESULTS: Five articles, involving 428 participants at various stages of CKD were included. Three studies diagnosed by the cross-sectional area (CSA) of the rectus femoris, while two others by muscle thickness (MT) and shear wave elastography (SWE) from the same muscle, separately. Overall, CSA or SWE had a pooled sensitivity of 0.95 (95% CrI, 0.80, 1.00), and the specificity was 0.73 (95% CrI, 0.55, 0.88) for diagnosing sarcopenia in CKD patients. CONCLUSIONS: Ultrasound measurements of CSA and SWE were more sensitive for diagnosing sarcopenia in the CKD population than in the general population. Ultrasound assessment from a single peripheral skeletal muscle site may serve as a rapid screening tool for identifying sarcopenic individuals within the CKD population, if a specific cut-off value could be determined.

CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.

Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

Alleviation of Oxidative Stress during Hemodialysis Sessions by Hemodialysis Membrane Innovation: A Multidisciplinary Perspective.

Oxidative stress is prevalent in end-stage kidney disease patients receiving chronic hemodialysis and is associated with heavy cardiovascular disease burdens and increased mortality risks. Hemoincompatible hemodialysis membranes per se contribute to the activation of oxidative reactions and the generation of oxygen free radicals. Since the early 1990s, vitamin E-coated membranes have been extensively used in hemodialysis patients to reduce oxidative stress during hemodialysis sessions. However, the beneficial effects of vitamin E-coated membranes versus unmodified synthetic membranes on long-term patient-centered outcomes, such as survival, quality of life, and prevalence of cardiovascular diseases, remain controversial. Accordingly, novel antioxidant hemodialysis membranes were prepared to replace the use of vitamin E-coated membranes despite the translational research on these membranes unfortunately coming to a standstill. In this review, we first summarize the state-of-the-art on the use of vitamin E-coated membranes in hemodialysis patients to highlight their strengths and limitations. Then, we discuss the latest advances in fabricating antioxidant hemodialysis membranes and provide perspectives to bridge knowledge gaps between laboratorial investigations and clinical practice in fabricating antioxidant hemodialysis membranes.

Atorvastatin reduces contrast media-induced pyroptosis of renal tubular epithelial cells by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI. METHODS: On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells. RESULTS: MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65). CONCLUSION: Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.

'Stress hyperglycemia ratio and in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.

OBJECTIVE: To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)- 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection. RESULTS: Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection. CONCLUSIONS: Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes.

Ultraporous Polyquaternium-Carboxylated Chitosan Composite Hydrogel Spheres with Anticoagulant, Antibacterial, and Rapid Endotoxin Removal Profiles for Sepsis Treatment.

Hemoperfusion is an important method to remove endotoxins and save the lives of patients with sepsis. However, the current adsorbents for hemoperfusion have disadvantages of insufficient endotoxin adsorption capacity, poor blood compatibility, and so on. Herein, we proposed a novel emulsion templating (ET) method to prepare ultraporous and double-network carboxylated chitosan (CCS)-poly(diallyl dimethylammonium chloride) (PDDA) hydrogel spheres (ET-CCSPD), bearing both negative and positive charges. CCS was introduced to balance the strong positive charges of PDDA to improve hemocompatibility, and emulsion templates endowed the adsorbent with an ultraporous structure for enhanced adsorption efficacy. The ET-CCSPDs neither damaged blood cells nor activated complement responses. In addition, the activated partial thromboplastin time (APTT) was prolonged to 8.5 times, which was beneficial for reducing the injection of anticoagulant in patients. The ET-CCSPDs had excellent scavenging performance against bacteria and endotoxin, with removal ratios of 96.7% for E. coli and 99.8% for S. aureus, respectively, and the static removal ratio of endotoxin in plasma was as high as 99.1% (C0 = 5.50 EU/mL, critical illness level). An adsorption cartridge filled with the ET-CCSPDs could remove 84.7% of endotoxin within 1 h (C0 = 100 EU/mL in PBS). Interestingly, the ET-CCSPDs had a good inhibitory effect on the cytokines produced by endotoxin-mediated septic blood. By developing the ET method to prepare ultraporous and double-network adsorbents, the problems of low adsorption efficiency and poor blood compatibility of traditional endotoxin adsorbents have been solved, thus opening a new route to fabricate absorbents for blood purification.

The value of urinary interleukin-18 in predicting acute kidney injury: a systematic review and meta-analysis.

AIMS: The aim of this study was to systematically review relevant studies to evaluate the value of urinary interleukin-18 (uIL-18) in predicting acute kidney injury (AKI). METHODS: A comprehensive search of PubMed, Medline, Embase, and Cochrane Library was conducted for literature published up to 1 August 2022. Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was applied to assess the literature quality. Then, relevant data were extracted from each eligible study and a random-effects regression model was utilized to pool sensitivity, specificity, and construct summary receiver operating characteristic (SROC) and area under curve (AUC). RESULTS: Twenty-six studies with 7183 patients were enrolled and relevant information was extracted. The estimated sensitivity and specificity of uIL-18 in the diagnosis of AKI were 0.64 (95% confidence interval (CI): 0.54-0.73) and 0.77 (95%CI: 0.71-0.83), respectively. The pooled diagnostic odds ratio (DOR) was 6.08 (95%CI: 3.63-10.18), and the AUC of uIL-18 in predicting AKI was 0.78 (95%CI: 0.74-0.81). Subgroup analysis showed that uIL-18 in pediatric patients was more effective in predicting AKI than in adults (DOR: 7.33 versus 5.75; AUC: 0.81 versus 0.77). CONCLUSIONS: Urinary IL-18 could be a relatively good biomarker with moderate predictive value for AKI, especially in pediatric patients. However, further research and clinical settings are still needed to validate our findings.

The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: a systematic review and Bayesian meta-analysis.

INTRODUCTION: The aim of the study was to systematically review relevant studies to evaluate the diagnostic value of urinary kidney injury molecule 1 (uKIM-1) for acute kidney injury (AKI) in adults. METHOD: We searched PubMed and Embase for literature published up to November 1st, 2019 and used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. Then, we extracted useful information from each eligible study and pooled sensitivity, specificity, and area under the curve (AUC) values. RESULTS: A total of 14 studies with 3300 patients were included. The estimated sensitivity of urinary KIM-1 (uKIM-1) in the diagnosis of AKI was 0.74 (95% CrI 0.62-0.84), and the specificity was 0.84 (95% CrI, 0.76-0.90). The pooled diagnostic odds ratio (DOR) was 15.22 (95% CrI, 6.74-42.20), the RD was 0.55 (95% CrI 0.43-0.70), and the AUC of uKIM-1 in diagnosing AKI was 0.62 (95% CrI 0.41-0.76). The results of the subgroup analysis showed the influence of different factors. CONCLUSION: Urinary KIM-1 is a good predictor for AKI in adult patients with relatively high sensitivity and specificity. However, further research and clinical trials are still needed to confirm whether and how uKIM-1 can be commonly used in clinical diagnosis.

Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patients: a systemic review and meta-analysis.

BACKGROUND: Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal anticoagulant strategy has not yet been defined. The objective of this meta-analysis was to investigate the effect of intermediate-to-therapeutic versus prophylactic anticoagulation for thromboprophylaxis on the primary outcome of in-hospital mortality and other patient-centered secondary outcomes in COVID-19 patients. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched from inception to August 10th 2021. Cohort studies and randomized clinical trials that assessed the efficacy and safety of intermediate-to-therapeutic versus prophylactic anticoagulation in hospitalized COVID-19 patients were included. Baseline characteristics and relevant data of each study were extracted in a pre-designed standardized data-collection form. The primary outcome was all-cause in-hospital mortality and the secondary outcomes were incidence of thrombotic events and incidence of any bleeding and major bleeding. Pooled analysis with random effects models yielded relative risk with 95 % CIs. RESULTS: This meta-analysis included 42 studies with 28,055 in-hospital COVID-19 patients totally. Our pooled analysis demonstrated that intermediate-to-therapeutic anticoagulation was not associated with lower in-hospital mortality (RR=1.12, 95 %CI 0.99-1.25, p=0.06, I2=77 %) and lower incidence of thrombotic events (RR=1.30, 95 %CI 0.79-2.15, p=0.30, I2=88 %), but increased the risk of any bleeding events (RR=2.16, 95 %CI 1.79-2.60, p<0.01, I2=31 %) and major bleeding events significantly (RR=2.10, 95 %CI 1.77-2.51, p<0.01, I2=11 %) versus prophylactic anticoagulation. Moreover, intermediate-to-therapeutic anticoagulation decreased the incidence of thrombotic events (RR=0.71, 95 %CI 0.56-0.89, p=0.003, I2=0 %) among critically ill COVID-19 patients admitted to intensive care units (ICU), with increased bleeding risk (RR=1.66, 95 %CI 1.37-2.00, p<0.01, I2=0 %) and unchanged in-hospital mortality (RR=0.94, 95 %CI 0.79-1.10, p=0.42, I2=30 %) in such patients. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from very low to moderate. CONCLUSIONS: We recommend the use of prophylactic anticoagulation against intermediate-to-therapeutic anticoagulation among unselected hospitalized COVID-19 patients considering insignificant survival benefits but higher risk of bleeding in the escalated thromboprophylaxis strategy. For critically ill COVID-19 patients, the benefits of intermediate-to-therapeutic anticoagulation in reducing thrombotic events should be weighed cautiously because of its association with higher risk of bleeding. TRIAL REGISTRATION: The protocol was registered at PROSPERO on August 17th 2021 ( CRD42021273780 ).

Predictors of successful discontinuation from renal replacement therapy during AKI: A meta-analysis.

The predictors of weaning time of renal replacement therapy (RRT) remain controversial for special patients suffering from acute kidney injury (AKI). The present work aims to perform a meta-analysis to evaluate proper predictors of RRT weaning in AKI patients. We systematically searched EMBASE, PubMed, and Cochrane Central Register of Controlled trials for literatures between 1984 and June 2019. Studies evaluating predictors of weaning success of RRT in patients of AKI were included. Random-effects model or fixed-effects model meta-analyses were performed to compute a standard mean difference (SMD). Newcastle-Ottawa Scale was employed to assess the risk of bias. We included 10 observational trials including 1453 patients. Twelve predictors including urine output, serum creatinine, serum urea, mean arterial pressure, central venous pressure, lactate, serum potassium, serum bicarbonate, pH value, SOFA score, urinary urea, and urinary creatinine were identified, showing urine output (p = 0.0000), serum creatinine (p = 0.008), serum potassium (p = 0.02), serum bicarbonate (p = 0.01), pH value (p = 0.03), urinary urea (p = 0.002), and urinary creatinine (p = 0.02) were significantly associated with weaning success. With the limited evidence, we speculate that urine output, serum creatinine, serum potassium, serum bicarbonate, pH value, urinary urea, and urinary creatinine might be associated with successful weaning.

Low lean mass and cognitive performance: data from the National Health and Nutrition Examination Surveys.

BACKGROUND: Low lean mass and cognitive impairment are both age-related diseases. In addition, these conditions share many risk factors. However, the association between them has been controversial in recent years. OBJECTIVE: To investigate the association between low lean mass and cognitive performance in U.S. adults using NHANES data from 1999 to 2002. METHODS: A total of 2550 participants were identified in the National Health and Nutrition Examination Survey Database (1999-2002). The independent variable was low lean mass, and the dependent variable was cognitive performance. Men and women were classified as having low lean mass if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was < 0.789 and < 0.512, respectively. Cognitive performance was assessed using the Digit Symbol Substitution Test (DSST). Higher scores on the DSST indicated better cognitive performance. The covariates included sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. RESULTS: For the primary outcome, our multivariate linear regression analysis indicated that participants without low lean mass were associated with better cognitive performance (ß = 1.50; 95% CI [0.12-2.89]). Subgroup analysis results indicated that the association was similar in sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. CONCLUSIONS: Participants without low lean mass were associated with better cognitive performance. We might be able to improve cognitive performance by treating low lean mass, thus providing an opportunity for intervention at a younger age.

Visceral Fat Area Is a Better Predictor Than Coronary Artery Calcification Score for Cardiovascular Outcomes and All-Cause Death in Patients on Hemodialysis.

OBJECTIVES: The aim of this study is to compare the prognostic effects of visceral fat area (VFA) with coronary artery calcification score (CACs) in patients on maintenance hemodialysis. DESIGN AND METHODS: In the prospective study with no intervention, clinical characteristics and serum biochemical indexes at baseline for each patient were collected through the electronic medical records. Body composition assessment using bioelectrical impedance analysis, computed tomography examination with the Agatston scoring method, and echocardiographic measurements were performed at enrollment. Primary endpoints included cardiovascular events (CVEs), cardiovascular death (CVD), and all-cause death. RESULTS: A total of 97 Chinese patients aged 48 (35-62) years were enrolled from our Hemodialysis Center, of which 61.9% were male and 20.6% had diabetes. The median of VFA and CACs at baseline was 64.5 (43.5-88.7) cm2 and 0.9 (0-467.6), respectively. CVEs occurred in 20 (20.6%) patients during a median follow-up of 26.4 (13-27.7) months. The cardiovascular and all-cause mortality was 8.2% (8 patients) and 11.3% (11 patients), respectively. VFA was associated with CVEs (hazard ratio [HR] = 9.21 for VFA ≥71.3 cm2 vs. VFA <71.3 cm2, P = .017), CVD (HR = 1.11 for 1 cm2 increase, P = .035), and all-cause mortality (HR = 1.08 for 1 cm2 increase, P = .011). Also, VFA was significantly correlated with cardiac structure parameters and the development of left ventricular hypertrophy (odds ratio = 1.02 for 1 cm2 increase, P = .03). Yet, CACs were not correlated with CVEs, CVD, or all-cause mortality. CONCLUSIONS: Increased VFA can be used as an independent predictor for CVEs, CVD, and all-cause mortality. The effect VFA exerts on cardiac reconstruction might be the underlying mechanism. Further studies are warranted for the management of VFA in the hemodialysis population.

Vascular calcification is associated with Wnt-signaling pathway and blood pressure variability in chronic kidney disease rats.

AIM: Vascular calcification (VC) is a common complication in chronic kidney disease (CKD) and has been shown to be associated with increased cardiovascular events and mortality. This study was to explore the role of Wnt-signaling pathway in CKD VC, and the association between VC and blood pressure variability (BPV) which is a risk factor of cardiovascular events. METHODS: Adult male Sprague-Dawley rats were divided into adenine-induced CKD group (n = 5), 5/6 nephrectomy CKD group (n = 5), sham group (n = 5) and control group (n = 5). Low-calcium-high-phosphate diets were introduced to induce vascular calcification. Both daytime (hour-to-hour during the day) and mid-term (day-to-day for 9 days) blood pressure (BP) were collected and analyzed for BPV metrics. At sacrifice, kidney, heart and aorta samples were taken for histological analyses. Calcium deposition in aorta was identified with Alizarin Red stain and graded. Immunohistochemistry stain and western blot were performed for Wnt3a, Wnt5a, ß-catenin, sclerostin, osteopontin, and α-SMA. RESULTS: Compared with control rats, CKD rats suffered from markedly severer VC (Grade 2.6 ± 0.2 and 1.8 ± 0.8 vs 0.0 ± 0.0 and 0.2 ± 0.4, P = .0010). VC was positively correlated with vascular Wnt3a and ß-catenin expression (P = .0032 and .0000), but not significantly associated with Wnta5a or sclerostin. Besides, CKD rats showed increased BPV (P < .001), which was also positively correlated with VC. CONCLUSION: We confirmed that CKD rats had enhanced Wnt-signaling in vascular tissue and severer aorta calcification together with increased BPV. Wnt pathway may be a potential target in future VC and BPV management in CKD.

Association of mineral content outside of bone with coronary artery calcium and 1-year cardiovascular prognosis in maintenance hemodialysis patients.

Coronary artery calcifications (CACs) are common among maintenance hemodialysis (MHD) patients and associated with increased morbidity and mortality due to cardiovascular events. The insight into chronic kidney disease-mineral and bone disorder (CKD-MBD) established a correlation between dysregulated mineral metabolism and CACs. This study aimed to identify the association of mineral content outside of bone (MCOB) with CACs and cardiovascular events in MHD patients. In the pilot prospective study with no intervention, patients underwent body composition assessment by body composition monitor after hemodialysis and computed tomography examination using the Agatston scoring method simultaneously within a week. The primary end point included cardiovascular events and cardiovascular death. Correlations and receiver operating characteristic analysis elucidated the associations of MCOB with CACs; multivariate analysis assessed the cardiovascular risk for groups with different MCOB. One hundred three eligible patients with an average age of 48 (35-63) years old were enrolled and followed up to 12 (11-12.5) months, among which 52.4% had detectable CACs at baseline. MCOB showed an inverse correlation with Agatston score and significantly discriminated the patients with Agatston score > 0 (AUC = 0.737; P < 0.001) and 400 (AUC = 0.733; P < 0.001). MCOB ≤ 9.2657 mg/kg was an independent risk factor for CACs (OR = 4.853; P = 0.044) and strong predictor for cardiovascular morbidity and mortality (HR = 10.108; P = 0.042), as well as rehospitalization (HR = 2.689; P = 0.004). MCOB inversely correlated with the presence and extent of CACs, and could discriminate Agatston score > 0 and 400, which also presented as an independent indicator for CKD-MBD and 1-year cardiovascular prognosis in adult MHD patients. Additional studies are required for identifying this issue.

The Association between Long- and Intra-Dialytic Blood Pressure Variability with All-Cause Mortality in Hemodialysis Patients.

BACKGROUND: Blood pressure variability (BPV) is a potential prognostic predictor for all-cause mortality. OBJECTIVES: We conducted a retrospective cohort study to compare the prognostic value of long-term BPV with intra-dialytic BPV in hemodialysis (HD) patients. MATERIALS AND METHODS: We included 611 HD patients and collected their baseline blood pressure (BP) measurements for 1 year and monitored them for 40 months. Long-term BPV was assessed by pre-dialysis BP SD and pre-dialysis absolute BP residual metric. Intra-dialytic BPV was assessed by intra-dialytic BP average real variability and intra-dialytic absolute BP residual. RESULTS: Long-term systolic BPV showed a weak correlation with mean BP, but a stronger correlation with intra-dialytic BPV. High long-term systolic blood pressure (SBP) SD and long-term SBP residual metrics were associated with high all-cause mortality (p = 0.0084 and 0.0056, respectively), while no such association was found for intra-dialytic BPV or diastolic BPV. According to receiver operating characteristic curve with mortality as dependent variable, long-term SBP residual metric showed the strongest prognostic ability (area under curve [AUC] 0.679, p = 0.0006), which was even stronger in patients with BP ≥140/90 mm Hg (AUC 0.713, p = 0.0004). After completely adjusting for confounders, long-term SBP residual metric remained significantly associated with all-cause mortality (hazard ratio 1.628 per quartile; 95% CI 1.086-2.441). CONCLUSIONS: Our results suggest long-term SBP residual metric to be a better predictor of all-cause mortality in HD patients, which could be used as an additional target for BP management.

Association of Peridialysis Blood Pressure and Its Variability with Cardiovascular Events in Hemodialysis Patients.

BACKGROUND/AIMS: Blood pressure variability (BPV) is a novel cardiovascular risk factor for the population undergoing hemodialysis (HD). METHODS: We conducted a retrospective cohort study of 526 HD patients. Four short-term peridialysis BPV metrics were analyzed: systolic blood pressure (SBP) change, SBP coefficient of variation (CV), SBP intradialytic average real variability (ARV), and absolute SBP residual. Multi variate analysis with Cox regression models were used to account for the potential confounders. RESULTS: Short-term BPV is found to be affected by age, pre-dialysis SBP, antihypertensive drugs, dialysis time, and vascular access. Calcium-channel blockers (CCBs) were found to be associated with lower BPV than those on non-CCB therapy or no antihypertensive drugs. Patients dialyzed in the morning had a greater absolute SBP change than those dialyzed in the afternoon or evening. Patients using fistulas had a lower BPV than catheters. Higher BPV metrics including SBP CV (unadjusted hazard ratio [HR]: 1.37, 95% confidence interval [CI] 1.14-1.66, p=0.001), SBP intradialytic ARV (unadjusted HR: 1.46, 95% CI: 1.20-1.77, p< 0.001), and SBP residual (unadjusted HR: 1.47, 95% CI: 1.21-1.79, p< 0.001) were associated with a greater risk of cardiovascular events. After complete multivariate adjustment for other potential confounders, the HR remained statistically significant for SBP intradialytic ARV (HR 1.31, 95% CI: 1.04-1.66, p=0.024). CONCLUSION: Peridialytic BPV may be a potential target for improved blood pressure (BP) management in HD patients. Each short-term BPV metric has different advantages and disadvantages and should be applied according to the clinical context and purpose.

[Quantitative Assessment of Skin Thickness using High Frequency Ultrasound in Systemic Sclerosis].

OBJECTIVE: To investigate the performance of high frequency ultrasound in the assessment of skin thickness in patients with systemic sclerosis (SSc). METHODS: The study included 82 SSc (SSc group) and 67 healthy volunteers (control group) from 2014 to 2016. The skin thickness at bilateral middle fingers and forearms,anterior chest and abdominal wall was measured using high frequency ultrasound. All the patients with SSc underwent the modified rodnan skin score (mRSS) over 17 anatomical sites by an experienced dermatologist. The differences in age,sex,height,body mass,body mass index (BMI) and skin thickness between SSc patients and healthy controls were compared. Receiver operating characteristic (ROC) curve analysis was performed to determine the performance of high frequency ultrasound in the differentiation of SSc from healthy skin,and the correlation of mRSS with skin thickness were analyzed. RESULTS: SSc patients and healthy controls shared similar demographic features (age,sex ratio,height,body mass,BMI) (P>0.05). Skin thickness values in SSc patients were increased significantly at fingers and forearms compared with healthy controls (P<0.05). The area under the curve (AUC) was 0.938, 0.905, 0.608, 0.586, 0.398, 0.321 at right and left finger,right and left forearm,chest and abdominal wall. Among them,AUC>0.9 of right and left fingers can be used for diagnosis,The skin thickness cut-off value for determining the diagnosis of SSc were as follows: 1.35 mm at the right finger with 84.1% sensitivity and 95.5% specificity,1.26 mm at the right forearm with 86.6% sensitivity and 89.6% specificity,respectively. Skin thickness increased significantly with mRSS. The correlation of total mRSS scores with total skin thickness was 0.599 (P<0.001),and the correlation of local mRSS score with local skin thickness were 0.400-0.623 (P<0.001),with the highest correlation coefficient at right finger and the lowest at abdomen. CONCLUSION: High frequency ultrasound may reflect extent of skin involvement of SSc,and skin thickness assessed with high frequency ultrasound appeared to be highly specific and sensitive at fingers.

Predictive Factors Upon Discontinuation of Renal Replacement Therapy for Long-Term Chronic Dialysis and Death in Acute Kidney Injury Patients.

The specific timing for discontinuing renal replacement therapy (RRT) in acute kidney injury (AKI) patients is debatable. The predictive abilities of variables at the time of discontinuation of RRT for the long-term prognoses of patients have not been explored. This study aimed to explore the prognostic factors upon discontinuation of RRT for long-term chronic dialysis and death of patients with acute RRT-requiring AKI, thus improving decision making regarding the discontinuation of RRT and the follow-up of patients thereafter. A cohort of 302 AKI patients who required acute RRT and remained alive and free of dialysis for at least 30 days after discharge from January 2009 to December 2012 were followed up. The predictive abilities of general characteristics, RRT details, and variables upon discontinuation of RRT for long-term chronic dialysis and all-cause death were evaluated using Cox proportional hazards models. Kaplan-Meier analysis with a log-rank test was used to compare the survival curves between the strata of levels of good predictors upon discontinuation of RRT. After a median follow-up time of 4.1 years, 20 (6.6%) patients initiated chronic dialysis and 56 (18.5%) patients died. A higher CysC level upon discontinuation of RRT (HR 1.520, 95% CI 1.082-2.135; P = 0.016), comorbid chronic kidney disease, and a higher non-renal Charlson comorbidity index (CCI) were independently predictive for chronic dialysis. The hemoglobin level upon discontinuation of RRT was inversely predictive of death (HR 0.986, 95% CI 0.973-0.999; P = 0.035), and comorbid malignancy, the presence of multiple organ dysfunction syndrome, and a higher non-renal CCI also predicted death. Urine output upon discontinuation of RRT was marginally inversely predictive of death (HR 0.997, 95% CI 0.994-1.000; P = 0.056). Patients who discontinued RRT with CysC levels <2.97 mg/L, hemoglobin levels >85 g/L, and urine output >1130 mL/24 h showed significantly higher non-chronic dialysis and survival rates according to a log-rank test. Our study suggested that upon discontinuation of RRT, higher serum CysC levels had the most promising predictive value for long-term chronic dialysis, and lower hemoglobin levels predicted long-term death; lower urine output also marginally predicted long-term death. Based on the remission of the comprehensive condition, lower CysC levels and higher hemoglobin levels and urine output should be considered in the decision to stop RRT. Patients showing worse levels of these indices upon discontinuation of RRT should undergo stricter follow-up and treatment to improve long-term outcomes.