Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

CircRNAs: versatile players and new targets in organ fibrosis.

Organ fibrosis can occur in virtually all major organs with relentlessly progressive and irreversible progress, ultimately resulting in organ dysfunction and potentially death. Unfortunately, current clinical treatments cannot halt or reverse the progression of fibrosis to end-stage organ failure, and thus, advanced antifibrotic therapeutics are urgently needed. In recent years, a growing body of research has revealed that circular RNAs (circRNAs) play pivotal roles in the development and progression of organ fibrosis through highly diverse mechanisms of action. Thus, manipulating circRNAs has emerged as a promising strategy to mitigate fibrosis across different organ types. In this review, we systemically summarize the current state of knowledge about circRNA biological properties and the regulatory mechanisms of circRNAs. A comprehensive overview of major fibrotic signaling pathways and representative circRNAs that are known to modulate fibrotic signals are outlined. Then, we focus on the research progress of the versatile functional roles and underlying molecular mechanisms of circRNAs in various fibrotic diseases in different organs, including the heart, liver, lung, kidney and skin. Finally, we offer a glimpse into the prospects of circRNA-based interference and therapy, as well as their utilization as biomarkers in the diagnosis and prognosis of fibrotic diseases. Video abstract.

Roles of Twist1 in lipid and glucose metabolism.

The abnormal lipid and glucose metabolisms are linked to the metabolic disorders, tumorigenesis, and fibrotic diseases, which attracts the increasing attention to find out the key molecules involved in the lipid and glucose metabolism as the possible therapeutic targets on these diseases. A transcriptional factor Twist1 has been associated with not only the embryonic development, cancer, and fibrotic diseases, but also the regulation of lipid and glucose metabolism. In this review, we will discuss the roles and mechanisms of Twist1 in the obesity-associated white adipose tissue inflammation and insulin resistance, brown adipose tissue metabolism, fatty acid oxidation, and glucose metabolism in skeletal muscle to provide a rational perspective to consider Twist1 as a potential treatment target in clinic. Video Abstract.

Diagnostic accuracy of the 3-minute diagnostic interview for confusion assessment method-defined delirium in delirium detection: a systematic review and meta-analysis.

BACKGROUND: Delirium is a common complication clinically and is associated with the poor outcomes, yet it is frequently unrecognised and readily disregarded. Although the 3-minute diagnostic interview for confusion assessment method-defined delirium (3D-CAM) has been used in a variety of care settings, a comprehensive evaluation of its accuracy in all available care settings has not been performed. OBJECTIVE: This study aimed to evaluate the diagnostic test accuracy of the 3D-CAM in delirium detection through a systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL (EBSCO) and ClinicalTrials.gov published from inception to 10 July 2022. The quality assessment of the diagnostic accuracy studies-2 tool was applied to evaluate methodological quality. A bivariate random effects model was used to pool sensitivity and specificity. RESULTS: Seven studies with 1,350 participants and 2,499 assessments were included, which were carried out in general medical wards, intensive care units, internal medical wards, surgical wards, recovery rooms and post-anaesthesia care units. The prevalence of delirium ranged from 9.1% to 25%. The pooled sensitivity and specificity were 0.92 (95% confidence interval [CI] 0.87-0.95) and 0.95 (95% CI 0.92-0.97), respectively. The pooled positive likelihood ratio was 18.6 (95% CI 12.2-28.2), the negative likelihood ratio was 0.09 (95% CI 0.06-0.14) and the diagnostic odds ratio was 211 (95% CI 128-349). Moreover, the area under the curve was 0.97 (95% CI 0.95-0.98). CONCLUSIONS: The 3D-CAM has good diagnostic accuracy for delirium detection in different care settings. Further analyses illustrated that it had comparable diagnostic accuracy in older adults and patients with dementia or known baseline cognitive impairment. In conclusion, the 3D-CAM is recommended for clinical delirium detection.

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3.

Renal interstitial fibrosis is the pathological basis of end-stage renal disease, in which the heterogeneity of macrophages in renal microenvironment plays an important role. However, the molecular mechanisms of macrophage plasticity during renal fibrosis progression remain unclear. In this study, we found for the first time that increased expression of Twist1 in macrophages was significantly associated with the severity of renal fibrosis in IgA nephropathy patients and mice with unilateral ureteral obstruction (UUO). Ablation of Twist1 in macrophages markedly alleviated renal tubular injury and renal fibrosis in UUO mice, accompanied by a lower extent of macrophage infiltration and M2 polarization in the kidney. The knockdown of Twist1 inhibited the chemotaxis and migration of macrophages, at least partially, through the CCL2/CCR2 axis. Twist1 downregulation inhibited M2 macrophage polarization and reduced the secretion of the profibrotic factors Arg-1, MR (CD206), IL-10, and TGF-ß. Galectin-3 was decreased in the macrophages of the conditional Twist1-deficient mice, and Twist1 was shown to directly activate galectin-3 transcription. Up-regulation of galectin-3 recovered Twist1-mediated M2 macrophage polarization. In conclusion, Twist1/galectin-3 signaling regulates macrophage plasticity (M2 phenotype) and promotes renal fibrosis. This study could suggest new strategies for delaying kidney fibrosis in patients with chronic kidney disease.

Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy.

BACKGROUND: Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified. METHODS: We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing. RESULTS: Decreased α-diversity (Shannon, P=0.03), altered microbial composition (Adonis, P=0.0001), and a striking expansion of the taxonomic chain Proteobacteria-Gammaproteobacteria-Enterobacteriales-Enterobacteriaceae-Escherichia-Shigella (all P<0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which Escherichia-Shigella contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN. CONCLUSION: Gut dysbiosis, characterized by a striking expansion of genus Escherichia-Shigella, is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of Escherichia-Shigella in IgAN pathogenesis.

Heparin anticoagulation versus regional citrate anticoagulation for membrane therapeutic plasma exchange in patients with increased bleeding risk.

Background Heparin anticoagulation (HA) is commonly employed for membrane therapeutic plasma exchange (mTPE). However, for patients with increased bleeding risk, there were controversial opinions on the use of HA versus regional citrate anticoagulation (RCA) for mTPE. Our present study aimed to evaluate the efficacy and safety of HA vs. RCA for mTPE in patients with increased bleeding risk.Methods Patients with increased bleeding risk who underwent mTPE between 2014 and 2021 in our center were screened. Observations of anticoagulation efficacy and safety were used as the study endpoints.Results A total of 108 patients with 368 mTPE sessions were included. Of the included patients, 38 and 70 received HA and RCA mTPE, respectively. There was no significant difference in the clotting of extracorporeal circuits between the HA and RCA groups (4.1% vs. 4.4%, p = 0.605). More bleeding episodes were observed in the HA group compared to the RCA group (16.4% vs. 4.4% mTPE sessions, p < 0.001). The frequency of postoperative transfusion within 24 h (11% vs. 3.4%, p = 0.007) was significantly different in the HA and RCA group. Anticoagulation strategy (HA vs. RCA; OR 5.659, 95%CI 2.266-14.129; p < 0.001), and mean arterial pressure (prior treatment, OR 1.052, 95%CI 1.019-1.086; p = 0.002) were independent risk factors of bleeding episodes. At the end of mTPE treatment, the incidence of metabolic alkalosis (16.7% vs. 54.1%, p = 0.027) and hypocalcemia (41.7% vs. 89.2%, p = 0.001) was significantly different in the HA (n = 5, 12 sessions) and RCA (n = 22, 74 sessions) groups, respectively.Conclusion RCA is as effective as HA for mTPE. However, for patients with increased bleeding risk, RCA is associated with a lower risk of bleeding, compared with HA. With careful monitoring and timely adjustment, RCA most likely is a safe and effective anticoagulation option for mTPE in patients with increased bleeding risk.

Alterations of the gut microbiota in the lupus nephritis: a systematic review.

BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

Cell Profiling of Acute Kidney Injury to Chronic Kidney Disease Reveals Novel Oxidative Stress Characteristics in the Failed Repair of Proximal Tubule Cells.

Chronic kidney disease (CKD) is a major public health issue around the world. A significant number of CKD patients originates from acute kidney injury (AKI) patients, namely "AKI-CKD". CKD is significantly related to the consequences of AKI. Damaged renal proximal tubular (PT) cell repair has been widely confirmed to indicate the renal prognosis of AKI. Oxidative stress is a key damage-associated factor and plays a significant role throughout the development of AKI and CKD. However, the relationships between AKI-CKD progression and oxidative stress are not totally clear and the underlying mechanisms in "AKI-CKD" remain indistinct. In this research, we constructed unilateral ischemia-reperfusion injury (UIRI)-model mice and performed single-nucleus RNA sequencing (snRNA-seq) of the kidney samples from UIRI and sham mice. We obtained our snRNA-seq data and validated the findings based on the joint analysis of public databases, as well as a series of fundamental experiments. Proximal tubular cells associated with failed repair express more complete senescence and oxidative stress characteristics compared to other subgroups. Furthermore, oxidative stress-related transcription factors, including Stat3 and Dnmt3a, are significantly more active under the circumstance of failed repair. What is more, we identified abnormally active intercellular communication between PT cells associated with failed repair and macrophages through the APP-CD74 pathway. More notably, we observed that the significantly increased expression of CD74 in hypoxia-treated TECs (tubular epithelial cells) was dependent on adjacently infiltrated macrophages, which was essential for the further deterioration of failed repair in PT cells. This research provides a novel understanding of the process of AKI to CKD progression, and the oxidative stress-related characteristics that we identified might represent a potentially novel therapeutic strategy against AKI.

[Retrospective Analysis of the Effect of Uric Acid on the Prognosis of Immunoglobulin A Nephropathy With Stage 3-4 Chronic Kidney Disease]. / å°¿é ¸æ°´å¹³å¯¹æ ¢æ€§è‚¾è„ç— 3-4期IgAè‚¾ç— é¢„åŽå½±å“çš„å›žé¡¾æ€§åˆ†æž.

Objective: To investigate the effect of uric acid on the clinicopathological characteristics and prognosis of immunoglobulin A nephropathy (IgAN) in patients with stage 3-4 chronic kidney disease (CKD). Methods: The clinical and pathological data of 263 IgAN patients who had stage 3-4 CKD and who had confrimed diagosis through renal biopsy at the First Affiliated Hospital of Air Force Medical University between December 2008 and January 2020 were retrospectively collected. According to the levels of uric acid, the patients were divided into a hyperuricemia group (n=102) and a normal uric acid group (n=161), and the clinicopathological characteristics of the two groups were compared accordingly. With progression to end-stage renal disease or death as the endpoint event, the renal survival rate of the two groups was compared by the Kaplan-Meier method and the relationship between uric acid and the prognosis was analyzed by Cox regression and LASSO regression. Results: Compared with the normal uric acid group, the hyperuricemia group had a significantly higher proportion of male patients and patients with a history of hypertension, a significantly higher level of blood urea nitrogen, and lower levels of estimated glomerular filtration rate and high-density lipoprotein. In terms of pathology, patients in the hyperuricemia group had significantly higher proportion of glomerulosclerosis, higher mesangial hypercellularity, and higher tubular atrophy/interstitial fibrosis (P<0.05). Kaplan-Meier curve showed that there was a significant difference in renal survival rate between the two groups (P<0.0001). LASSO regression showed that high uric acid was a risk factor for the prognosis of IgAN patients with stage 3-4 CKD. Further multivariate Cox analysis showed that, compared with the normal uric acid group, the hyperuricemia group had a higher risk of incurring composite outcomes (hazard ratio [HR]=1.61, 95% confidence interval [CI]: 1.10-2.34). When uric acid was used as a continuous variable, the increase of 1 mg/dL in uric acid concentration was associated with an increased HR of 1.18 (95% CI: 1.08-1.29) for the composite outcome. Conclusion: High uric acid is a risk factor for poor renal prognosis in IgAN patients with stage 3-4 CKD and reducing uric acid levels may effectively improve the prognosis of high-risk IgAN patients.

[Role of Histone Modifications in Acute Kidney Injury Progressing to Chronic Kidney Disease]. / ç»„è›‹ç™½ä¿®é¥°åœ¨æ€¥æ€§è‚¾æŸä¼¤å‘æ ¢æ€§è‚¾è„ç— è½¬åŒ–ä¸­çš„ä½œç”¨.

Acute kidney injury (AKI), a clinical syndrome caused by various factors, is characterized by a rapid decline in kidney function in a short period of time. AKI affects the short-term prognosis of patients and may also induce chronic kidney disease (CKD). However, the current treatment options for AKI mainly focus on symptom management. Specific therapeutic measures available for the prevention of transition from AKI to CKD are very limited in number. Histones are basic proteins that intricately bind the DNA in chromosomes. After translation, histones undergo various modifications on their amino-terminal tails, such as methylation, acetylation, phosphorylation, ubiquitination, and lactylation, collectively forming the "histone code", which affects the expression of genes mainly by regulating the elastic structure of chromatin or recruiting specific proteins. Extensive research conducted in recent years on histone post-translational modifications (PTMs) has also sparked continuous interest in their association with the AKI-to-CKD transition. Therefore, this paper highlights the significant role of PTMs in the process of AKI developing and progressing to CKD, with a view to finding new approaches to preventing the progression of AKI to CKD.

Construction and evaluation of an integrated predictive model for chronic kidney disease based on the random forest and artificial neural network approaches.

Chronic kidney disease (CKD) is recognized as a serious global health problem due to its high prevalence and all-cause mortality. The aim of this research was to identify critical biomarkers and construct an integrated model for the early prediction of CKD. By using existing RNA-seq data and clinical information from CKD patients from the Gene Expression Omnibus (GEO) database, we applied a computational technique that combined the random forest (RF) and artificial neural network (ANN) approaches to identify gene biomarkers and construct an early diagnostic model. We generated ROC curves to compare the model with other markers and evaluated the associations of selected genes with various clinical properties of CKD. Moreover, we highlighted two biomarkers involved in energy metabolism pathways: pyruvate dehydrogenase kinase 4 (PDK4) and zinc finger protein 36 (ZFP36). The downregulation of the identified key genes was subsequently confirmed in both unilateral ureteral obstruction (UUO) and ischemia reperfusion injury (IRI) mouse models, accompanied by decreased energy metabolism. In vitro experiments and single-cell sequencing analysis proved that these key genes were related to the energy metabolism of proximal tubule cells and were involved in the development of CKD. Overall, we constructed a composite prediction model and discovered key genes that might be used as biomarkers and therapeutic targets for CKD.

Specific Alterations of Gut Microbiota in Chinese Patients with Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: China has the largest absolute burden of hypertension (HTN) in the world. Gut dysbiosis may be a potentially modifiable risk factor for HTN. However, the characteristics of gut microbiota in Chinese populations with HTN remain to be determined. METHODS: We systematically searched for studies comparing the gut microbial in HTN with healthy controls in databases. The cut-off date was December 30, 2021. Semiquantitative analysis and meta-analysis with standardized mean differences of the alteration in gut microbiota were carried out. RESULTS: A total of 16 studies involving 2,372 patients with HTN and 849 controls were included, covering 16 Chinese provinces or regions. The present study supports that compared to healthy population, the diversity of patients with HTN is significantly compromised, while richness is overall preserved. To be specific, a significant increase of the Firmicutes (F)/Bacteroidetes (B) ratio is considered as a special parameter of gut microbiota in HTN patients. The increased abundance of phylum Firmicutes, genus Megasphaera, Escherichia_Shigella, and Klebsiella while the lower abundance of phylum Bacteroidetes, genus Bifidobacterium, Faecalibacterium, Roseburia, and Ruminococcus may be associated with HTN. The gut microbial metabolism in HTN was more abundant in lipopolysaccharide biosynthesis, membrane transport, and steroid degradation. CONCLUSIONS: Variation in gut microbial parameters is likely associated with Chinese patients with HTN. Further investigations should distinguish geographical and ethnic characteristics to develop in-depth knowledge of the underlying mechanisms by which gut dysbiosis contributes to HTN.

Long-term outcomes of IgA nephropathy patients with less than 25% crescents and mild proteinuria.

BACKGROUND: Whether immunosuppressive therapy in IgA nephropathy (IgAN) patients with less than 25% crescents (C1) and mild proteinuria can improve the renal outcome is still unclear. METHODS: We recruited 140 IgAN patients with C1 and proteinuria < 1 g/24 h who received supportive care (n = 52) or steroid-based immunosuppressive therapy (n = 88) in Xijing Hospital from July 2008 to December 2016. The primary outcome was the rate of renal function decline. RESULTS: The median of proteinuria was 575.5 mg/24 h, the fraction of crescents was 7% (5%, 12%) and follow-up time was 69.1 months. The rate of renal function decline [0.5 (- 1.5, 3.2) vs - 0.7 (- 3.5, 0.5) ml/min per 1.73 m2 per year; P = 0.01] was slower in steroid-based immunosuppressive therapy group than supportive care group. Multivariate linear regression analyses showed steroid-based immunosuppressive therapy significantly slowed down the rate of renal function decline (ß = - 0.220, 95% CI - 3.804 to - 0.449, P = 0.013) after adjusting age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, the fraction of crescents and RASB. In the matched cohort, the rate of renal function decline was also slower in steroid-based immunosuppressive therapy group. The incidence of adverse events was similar between the two groups. CONCLUSION: Steroid-based immunosuppressive therapy may slow down the rate of renal function decline of IgAN patients with C1 and proteinuria ≤ 1 g/24 h.

Development and External Validation of a Model for Predicting Sufficient Filter Lifespan in Anticoagulation-Free Continuous Renal Replacement Therapy Patients.

BACKGROUND: Anticoagulation-free continuous renal replacement therapy (CRRT) was recommended by the current clinical guideline for patients with increased bleeding risk and contraindications of citrate. Nevertheless, anticoagulation-free CRRT yielded heterogeneous filter lifespan. Furthermore, the specific cutoff values for traditional coagulation parameters to predict sufficient filter lifespan of anticoagulation-free CRRT have not yet been determined. The purpose of our present study was to develop and validate a model for predicting sufficient filter lifespan in anticoagulation-free CRRT patients. METHODS: Patients who underwent anticoagulation-free CRRT in our center between June 2013 and June 2019 were retrospectively included. The primary outcome was sufficient filter lifespan (≥24 h). Thirty-seven predictors were included for modeling based on their clinical significance and previous reports. The final model was developed by using multivariable logistic regression analysis and was validated in a separate external cohort. RESULTS: The development cohort included 170 patients. Sufficient filter lifespan was observed in 80 patients. Thirteen variables were independent predictors for sufficient filter lifespan by logistic regression: body temperature, mean arterial pressure, activated partial thromboplastin time, direct bilirubin, alkaline phosphatase, blood urea nitrogen, vasopressor use, body mass index, white blood cell, platelet count, D-dimer, uric acid, and pH. The area under the curve (AUC) of the stepwise model and internal validation model was 0.82 (95% confidence interval [CI] [0.76-0.88]) and 0.8 (95% CI [0.74-0.87]), respectively. The positive predictive value and the negative predictive value of the stepwise model were 0.77 and 0.79, respectively. The validation cohort included 44 eligible patients and the AUC of the external validation model was 0.82 (95% CI [0.69-0.96]). CONCLUSIONS: The use of a prediction model instead of an assessment based only on coagulation parameters could facilitate the identification of the patients with filter lifespan of ≥24 h when they accepted anticoagulation-free CRRT.

Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

INTRODUCTION: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. METHODS: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (ß2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of ß2M and PTH, while the secondary outcome was the reduction of the pruritus score. RESULTS: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of ß2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. CONCLUSION: The long-term HP + HD can reduce ß2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Earlier continuous renal replacement therapy is associated with reduced mortality in rhabdomyolysis patients.

BACKGROUND: Continuous renal replacement therapy (CRRT) is commonly employed for rhabdomyolysis (RM) patients. However, the optimal initiation timing of CRRT and prognostic factors were not well evaluated for patients with RM. We aimed to investigate the efficacy of CRRT timing on mortality and the risk factors for death in RM patients who received CRRT. METHODS: RM patients who received CRRT between 1 May 2010 and 31 May 2021 in our center were retrospectively included. Univariate and multivariate logistic analyses were performed to identify the risk factors for primary outcome (90-day mortality). RESULTS: A total of 134 patients were included in our study. The 90-day mortality rate was 38.06%. The median time from CRRT initiation to peak CK occurrence was 4.8 h (IQR -16, 14), 67 patients received CRRT before 4.8 h after peak CK occurrence (early CRRT), and 67 patients received CRRT beyond 4.8 h after peak CK occurrence (late CRRT). Multivariate logistic regression analysis showed that the time from CRRT initiation to the peak CK (per 1 h, OR 1.026, 95% CI 1.004-1.049, p = 0.023), late CRRT (OR 3.082, 95% CI 1.072-8.859, p = 0.037), elevated serum cardiac troponin I (cTnI) (per 1 ng/mL, OR 1.218, 95% CI 1.011-1.468, p = 0.038), older age (per 1 year, OR 1.042, 95% CI 1.003-1.081, p = 0.032), and need of mechanical ventilation support (OR 4.632, 95% CI 1.292-16.61, p = 0.019) were independent risk factors for 90-day mortality. CONCLUSIONS: Earlier CRRT initiation before 4.8 h after peak CK occurrence was associated with lower 90-day patient mortality.

Association between serum advanced oxidation protein products and mortality risk in maintenance hemodialysis patients.

BACKGROUND: The association between serum advanced oxidation protein products (AOPP) and mortality risk remains equivocal. We aimed to assess the correlation of serum AOPP levels with the risk of all-cause mortality in hemodialysis (HD) patients. METHODS: A total of 1394 maintenance HD patients with complete data on AOPP and related parameters were included from China Collaborative Study on Dialysis (CCSD), a multi-center, prospective cohort study. The primary outcome was all-cause mortality, the secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 5.2 years (IQR, 2.1-5.4), all-cause mortality occurred in 492 (31.4%) participants. Overall, there was a reversed L-shaped association between serum AOPP and all-cause mortality in HD patients (P for nonlinearity = 0.04), with an inflection point at 87 µmol/L. Accordingly, there was no significant association between serum AOPP and all-cause mortality (per SD increment; HR, 0.94; 95%CI, 0.84, 1.05) in participants with AOPP < 87 µmol/L. However, there was a positive relationship of serum AOPP and all-cause mortality (per SD increment; HR, 1.24; 95%CI, 1.08, 1.42) in those with AOPP ≥ 87 µmol/L. Moreover, a similar trend was found for CVD mortality. CONCLUSIONS: Elevated serum AOPP levels were associated with higher risk of all-cause mortality in Chinese maintenance HD patients.

Prevalence and risk factors of relapse in patients with ANCA-associated vasculitis receiving cyclophosphamide induction: a systematic review and meta-analysis of large observational studies.

BACKGROUND: Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse. METHODS: We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed. RESULTS: Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10-0.14), 0.33 (0.29-0.38), and 0.47 (0.42-0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine). CONCLUSIONS: Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.