Micheliolide ameliorates lipopolysaccharide-induced acute kidney injury through suppression of NLRP3 activation by promoting mitophagy via Nrf2/PINK1/Parkin axis.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) represents a frequent complication of in critically ill patients. The objective of this study is to illuminate the potential protective activity of Micheliolide (MCL) and its behind mechanism against SA-AKI. METHODS: The protective potential of MCL on SA-AKI was investigated in lipopolysaccharide (LPS) treated HK2 cells and SA-AKI mice model. The mitochondrial damage was determined by detection of reactive oxygen species and membrane potential. The Nrf2 silencing was achieved by transfection of Nrf2-shRNA in HK2 cells, and Nrf2 inhibitor, ML385 was employed in SA-AKI mice. The mechanism of MCL against SA-AKI was evaluated through detecting hallmarks related to inflammation, mitophagy and Nrf2 pathway via western blotting, immunohistochemistry, and enzyme linked immunosorbent assay. RESULTS: MCL enhanced viability, suppressed apoptosis, decreased inflammatory cytokine levels and improved mitochondrial damage in LPS-treated HK2 cells, and ameliorated renal injury in SA-AKI mice. Moreover, MCL could reduce the activation of NLRP3 inflammasome via enhancing mitophagy. Additionally, Nrf2 deficiency reduced the suppression effect of MCL on NLRP3 inflammasome activation and blocked the facilitation effect of MCL on mitophagy in LPS-treated HK2 cells, the consistent is true for ML385 treatment in SA-AKI mice. CONCLUSIONS: MCL might target Nrf2 and further reduce the NLRP3 inflammasome activation via enhancing mitophagy, which alleviated SA-AKI.

Analysis of predictive factors of thrombosis in autogenous arteriovenous fistula.

PURPOSE: To investigate the predictors of early diagnosis of thrombus of autogenous arteriovenous fistula (aAVF). METHODS: The included patients were divided into the thrombus group with aAVF failure or thrombosis and the control group with good internal fistula function. The general data of the patients, including age, sex, diabetes mellitus, were collected. Platelets (PLT), platelet crit (P-LCR), platelet distribution width (PDW), mean platelet volume (MPV), homocysteine (HCY), and other biochemical data were collected. The predictors of thrombus of aAVF were obtained by the t test and logistic regression analysis, and receiver operating characteristic (ROC) curve analysis was used to compare the area under the ROC curve (AUC) between the combined predictors and the original indicators. The optimal critical value was determined when the Youden index reached its maximum value, and the sensitivity, specificity, accuracy, diagnostic index, and so on were calculated. Finally, prediction was performed by substituting each value in individually. RESULTS: PLT, PDW, P-LCR, MPV, and HCY showed significant differences between two groups (p < 0.05). Logistic regression analysis showed that, for PLT (OR = 1.014, 95% CI 1.006-1.022, p = 0.01), PDW (OR = 1.295, 95% CI 1.009-1.661, p = 0.042), P-LCR (OR = 1.230, 95% CI 1.089-1.389, p = 0.001), MPV (OR = 1.696, 95% CI 1.101-2.613, p = 0.017), and HCY (OR = 1.332, 95% CI 1.182-1.502, p = 0.01), the difference was significant; PLT, PDW, P-LCR, MPV, and HCY were positively correlated with thrombogenesis (p < 0.05). By logistic regression, a group of the five predictors of PLT, PDW, P-LCR, MPV, and HCY was obtained, and the combined predictors were 0.014*PLT + 0.258*PDW + 0.207*P-LCR + 0.528*MPV + 0.287*HCY. The area under the curve of the combined predictor was 0.933, the sensitivity was 92.4%, the specificity was 81.2%, the maximum diagnostic index was 0.736, the diagnostic cutoff point was 21.790, and the accuracy rate was 87%. CONCLUSION: PLT, PDW, P-LCR, MPV, and HCY are predictors of thrombus of aAVF. They can better predict thrombus of aAVF, and the combination of these five indicators is better than a single indicator.

Treatment Efficacy of Continuous Renal Replacement on Symptoms, Inflammatory Mediators, and Coagulation Function in Patients with Sepsis-Associated Acute Kidney Injury.

INTRODUCTION: The aim of this study is to compare the treatment efficacy between continuous renal replacement therapy (CRRT) and conventional intermittent hemodialysis (IHD) in patients with sepsis (SIRS) combined with acute kidney injury (AKI) and its impact on inflammatory mediators and coagulation function. METHOD: 122 patients (25-60 years) with SIRS combined with AKI were enrolled in the sudy. The study group (SG) comprised 62 patients who received CRRT (8-10 h/day) + routine treatment, whereas the control group (CG) comprised 60 patients who received conventional IHD (4 h/day, 3 times per week) + routine treatment. inflammatory mediators and coagulation function measures were assessed and compared in each group. RESULTS: C-reactive protein, blood creatinine, blood urea nitrogen, blood lactic acid, oxygenation index, central venous oxygen saturation, SOFA (Sequential Organ Failure Assessment) score, interleukin 6, interleukin 8, hypersensitive C-reactive protein, tumor necrosis factor-α, prothrombin time, activated partial thromboplastin time, FIB, and platelet count were better in the SG than in the CG (p < 0.05). The 12- and 24-month survival rates were significantly higher in the SG than in the CG (p < 0.05). CONCLUSIONS: CRRT can effectively improve clinical symptoms, remove inflammatory factors, and maintain blood coagulation function in patients with SIRS combined with AKI. It is more efficient than IHD treatment and is worthy of clinical promotion.

Effects of Uremic Clearance Granules on p38 MAPK/NF-κB Signaling Pathway, Microbial and Metabolic Profiles in End-Stage Renal Disease Rats Receiving Peritoneal Dialysis.

Background: End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In the clinic, Uremic Clearance Granules (UCG) are mainly used in the treatment of early CKD and stabilized renal function. However, the benefits and mechanisms of UCG on ESRD remain unclear. Methods: Rats were randomly divided into four groups: sham group, model group, peritoneal dialysis (PD) group and UCG group. Except for the sham-operated group, ESRD was induced by 5/6 nephrectomy in the other three groups. The PD group and UCG group were then subjected to PD. In addition, the UCG group was given UCG by gavage when PD. Changes in body weight and final kidney weight of rats in each group were monitored. HE and Masson staining were performed to confirm the extent of renal fibrosis. Biochemical kits were used to detect blood urea nitrogen (BUN), serum and urine creatinine (Scr, Cre), and urine protein (UPr) levels. ELISA was used to detect the rats' inflammatory responses. qRT-PCR, WB, and IHC were probed to determine the expression levels of NF-κB and MAPK. 16S rDNA sequencing was performed to analyze the composition of gut microbiota in rats. A liquid chromatograph-mass spectrometer was performed to reveal serum metabolomics changes. Results: UCG increased renal volume and body weight, improved renal fibrosis. It enhanced renal function and decreased the levels of BUN, Scr, Upr, Cre, inflammatory responses, as well as NF-κB and MAPK expressions in renal and colon tissues of ESRD rats. The relative abundances of Bacteroidetes and Firmicutes changed in ESRD rats in response to UCG. Serum metabolomics was utilized to identify 70 differentiated metabolites, which were associated with D-glutamine and D-glutamate metabolism, and Phenylalanine metabolism. Conclusion: Our study confirmed that UCG alleviated ESRD by regulating p38 MAPK/NF-κB signaling pathway, microbial and metabolic profiles.

Efficacy of continuous ambulatory peritoneal dialysis combined with hemodialysis versus single hemodialysis in patients with end-stage renal disease.

OBJECTIVE: This study aimed to compare the efficacy of single hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) combined with HD in the treatment of end-stage renal disease. METHODS: Seventy patients with end-stage renal disease in our hospital from January 2019 to December 2020 were included and divided into 35 patients in the single group (SG) and 35 patients in the combination group (CG) according to a random number table. The SG received HD treatment and the CG received CAPD combined with HD treatment. RESULTS: Hemoglobin and serum albumin levels were higher, blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower, and interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels were lower in the CG than in SG at the end of treatment (P < 0.05). Ca2+ levels were higher and P3+ levels were decreased at the end of treatment in both groups compared with those before treatment (P < 0.05), and Ca2+ and P3+ levels at the end of treatment in the CG were not different from those in the SG (P > 0.05). The complication rate in the CG was 5.71%, which was lower than 25.71% in the SG (P < 0.05). Quality of life scores were higher in the CG than in the SG at the end of treatment (P < 0.05). CONCLUSION: CAPD combined with HD can improve renal function and nutritional levels more significantly, control inflammatory responses more effectively, and reduce complications compared to single HD treatment in patients with end-stage renal disease.

Minimally invasive 'pull technique' for peritoneal dialysis catheter removal.

A simple, noninvasive method for removing peritoneal dialysis (PD) catheters, called the "pull technique," has become popular in recent years. Physicians still worry, however, about the range of its application and possible complications such as infection of the retained cuff and breakage. We, therefore, applied this technique in patients and enriched its administration for removing PD catheters. Altogether, 24 PD catheter removals in 24 patients were reviewed during the period from July 2018 to October 2019 in our hospital. Using the pull technique, the PD catheter's superficial cuff was dissected using an electronic knife, and the deep cuff was retained. All patients' catheters were successfully removed with no breakage. No incision or retained cuff was infected during the follow-up period (1.1-15.6 months). The appropriate peak force of pull traction was approximately 12-13 pounds, not very different from the mean maximum tensile force of 21.48 pounds for silicone tube breakage. The use of intermittent (rather than sustained) traction may reduce the breakage risk of the silicone tube. This method is a safe, practical, minimally invasive method for removing PD catheters, and it is suitable for application on special patients with peritonitis or who are on an immunosuppressant.

Treatment Efficacy of Continuous Renal Replacement on Symptoms, Inflammatory Mediators, and Coagulation Function in Patients with Sepsis-Associated Acute Kidney Injury

Introduction: The aim of this study is to compare the treatment efficacy between continuous renal replacement therapy (CRRT) and conventional intermittent hemodialysis (IHD) in patients with sepsis (SIRS) combined with acute kidney injury (AKI) and its impact on inflammatory mediators and coagulation function. Method: 122 patients (25–60 years) with SIRS combined with AKI were enrolled in the sudy. The study group (SG) comprised 62 patients who received CRRT (8–10 h/day) + routine treatment, whereas the control group (CG) comprised 60 patients who received conventional IHD (4 h/day, 3 times per week) + routine treatment. inflammatory mediators and coagulation function measures were assessed and compared in each group. Results: C-reactive protein, blood creatinine, blood urea nitrogen, blood lactic acid, oxygenation index, central venous oxygen saturation, SOFA (Sequential Organ Failure Assessment) score, interleukin 6, interleukin 8, hypersensitive C-reactive protein, tumor necrosis factor-α, prothrombin time, activated partial thromboplastin time, FIB, and platelet count were better in the SG than in the CG (p < 0.05). The 12- and 24-month survival rates were significantly higher in the SG than in the CG (p < 0.05). Conclusions: CRRT can effectively improve clinical symptoms, remove inflammatory factors, and maintain blood coagulation function in patients with SIRS combined with AKI. It is more efficient than IHD treatment and is worthy of clinical promotion (AU)