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Aim: Chemotherapy has been well shown to enhance life expectancy in patients with malignancy. However, conventional chemotherapy drugs, particularly cisplatin, are highly associated with nephrotoxicity, which limits therapeutic efficacy and impairs quality of life. Histone deacetylases (HDACs) are proteases that play significant roles in diseases by influencing protein post-translational modification and gene expression. Agents that inhibit HDAC enzymes have been developed and approved by the FDA as anticancer drugs. It is worth noting that in certain preclinical studies with tumour cell lines, the integration of HDAC modulators and cisplatin not only exerts synergistic or additive tumour-killing effects but also alleviates cisplatin nephrotoxicity. The aim of this review is to discuss the role of HDACs in cisplatin nephrotoxicity.Methods: After searching in PubMed and Web of Science databases using ‘Histone deacetylase’, ‘nephrotoxicity’, ‘cisplatin’, and ‘onconpehrology’ as keywords, studies related was compiled and examined.Results: HDAC inhibitors exert renal protective effects by inhibiting inflammation, apoptosis, oxidative stress, and promoting autophagy; whereas sirtuins play a renal protective role by regulating lipid metabolism, inhibiting inflammation and apoptosis, and protecting mitochondrial biosynthesis and mitochondrial dynamics. These potential interactions provide clues concerning targets for molecular treatment.Conclusion: This review encapsulates the function and molecular mechanisms of HDACs in cisplatin nephrotoxicity, providing the current view by which HDACs induce different biological signaling in the regulation of chemotherapy-associated renal injury. More importantly, this review exhaustively elucidates that HDACs could be targeted to develop a new therapeutic strategy in treating cisplatin nephrotoxicity, which will extend the knowledge of the biological impact and clinical implications of HDACs.

Introduction: Immunoglobulin A nephropathy (IgAN) patients with lower estimated glomerular filtration rate (eGFR) and higher proteinuria are at a higher risk for end-stage kidney disease (ESKD) and their prognosis is still unclear. We aim to develop and validate prognostic models in IgAN patients with CKD stage 3 or 4 and proteinuria≥1.0 g/d. Methods: Patients who came from Xijing Hospital, spanning December 2008 to January 2020 were divided into training and test cohorts randomly, with a ratio of 7:3, achieving ESKD and death as study endpoints. Created prediction models for IgAN patients based on 66 clinical and pathological characteristics using the random survival forests (RSF), survival support vector machine (SSVM), eXtreme Gradient Boosting (XGboost), and Cox regression models. The concordance index (C-index), integrated Brier scores (IBS), net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate discrimination, calibration, and risk classification respectively. Results: A total of 263 patients were enrolled. The median follow-up time was 57.3 months, with 124 (47.1%) patients experiencing combined events. Age, blood urea nitrogen, serum uric acid, serum potassium, glomeruli sclerosis ratio, hemoglobin, and tubular atrophy/interstitial fibrosis were identified as risk factors. The RSF model predicted the prognosis with a C-index of 0.871 (0.842, 0.900) in training cohort and 0.810 (0.732, 0.888) in test cohort, which was higher than the models built by SSVM model (0.794 (0.753, 0.835) and 0.805 (0.731, 0.879) respectively), XGboost model (0.840 (0.797, 0.883) and 0.799 (0.723, 0.875) respectively) and Cox regression (0.776 (0.727, 0.825) and 0.793 (0.713, 0.873) respectively). NRI and IDI showed that the RSF model exhibited superior performance than the Cox model. Conclusion: Our model introduced seven risk factors that may be useful in predicting the progression of IgAN patients with CKD stage 3 or 4 and proteinuria ≥1.0g/d. The RSF model is applicable for identifying the progression of IgAN and has outperformed than SSVM, XGboost, and Cox models.

Abstract 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

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan–Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637–78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109–3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166–66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

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.

AbstractBackground 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

Abstract 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

Background and objectives: The mortality rate for people with brain injuries is increased when hypernatremia is present. Patients with severe hypernatremia, who have a significant short-term mortality rate, were shown to benefit from continuous venovenous hemofiltration (CVVH), which has been indicated to be successful. Exploring the risk factors for short-term mortality in brain injury patients who underwent CVVH and had severe hypernatremia was the aim of the current study. Materials and methods: Retrospective screening was performed on patients with brain injuries who underwent CVVH at Xijing Hospital between 1 December 2010 and 31 December 2021 and who have a diagnosis of severe hypernatremia. The outcomes included 28-day patient mortality and hospital stay duration. The patient survival rate was examined using the Kaplan-Meier survival curve. To determine the risk factors for short-term death for patients, univariate and multivariate Cox regression analysis models were used. Results: Our current study included a total of 83 individuals. The included patients had a median age of 49 (IQR 35–59) years. Of the included patients, 58 patients (69.9 %) died within 28 days. The median length of hospital stay for the patient was 13 (IQR 7–21) days. The APACHE II score, SOFA score, GCS, PLT count, INR, stroke, mechanical ventilation, and vasopressor reliance were related to 28-day mortality according to the univariate Cox analysis. INR (HR = 1.004, 95 % Cl: 1.001–1.006, P = 0.008), stroke (HR = 1.971, 95 % Cl: 1.031–3.768, P = 0.04), mechanical ventilation (HR = 3.948, 95 % Cl: 1.090–14.294, P = 0.036), and vasopressor dependency (HR = 2.262, 95 % Cl: 1.099–4.655, P = 0.027) were independently associated with the risk of 28-day death rates, according to multivariate Cox regression analysis. Conclusions: Brain injuries who have severe hypernatremia requires CVVH, which has high short-term patient mortality. Mechanical ventilation, INR increase, stroke, and vasopressor dependence are independently associated with increased patient mortality risk.

Background The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. Methods Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. Results A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. Conclusion The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

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.

Hypernatremia is a common electrolyte disorder in patients with brain injury. The mortality of brain injury patients with severe hypernatremia may be as high as 86.8%. The efficacy of conventional treatment for hypernatremia is limited. Continuous renal replacement therapy (CRRT) can slowly, controllably, and continuously reduce the blood sodium concentration and gradually become an important treatment for severe hypernatremia patients. This review aims to provide important information for clinicians and clinical researchers by describing the etiology, diagnosis, hazards, conventional treatment, and CRRT treatment of hypernatremia in patients with traumatic brain injury.

Coronavirus disease 2019 (COVID-19) spread worldwide and presented a significant threat to people's health. Inappropriate disease assessment and treatment strategies bring a heavy burden on healthcare systems. Our study aimed to construct predictive models to assess patients with COVID-19 who may have poor prognoses early and accurately. This research performed a retrospective analysis on two cohorts of patients with COVID-19. Data from the Barcelona cohort were used as the training set, and data from the Rotterdam cohort were used as the validation set. Cox regression, logistic regression, and different machine learning methods including random forest (RF), support vector machine (SVM), and decision tree (DT) were performed to construct COVID-19 death prognostic models. Based on multiple clinical characteristics and blood inflammatory cytokines during the first day of hospitalization for the 138 patients with COVID-19, we constructed various models to predict the in-hospital mortality of patients with COVID-19. All the models showed outstanding performance in identifying high-risk patients with COVID-19. The accuracy of the logistic regression, RF, and DT models is 86.96, 80.43, and 85.51%, respectively. Advanced age and the abnormal expression of some inflammatory cytokines including IFN-α, IL-8, and IL-6 have been proven to be closely associated with the prognosis of patients with COVID-19. The models we developed can assist doctors in developing appropriate COVID-19 treatment strategies, including allocating limited medical resources more rationally and early intervention in high-risk groups.

Background: The pathogenesis of idiopathic membranous nephropathy (IMN) has not yet been thoroughly clarified, and gut dysbiosis may be a contributor to IMN. However, the characterization of gut microbiota in patients with IMN remains uncertain.Methods: Cochrane Library, PubMed, China National Knowledge Internet, Web of Science, and Embase were used to search for studies through 18 May 2022. A meta-analysis based on the standardized mean difference (SMD) with 95% confidence interval (CI) was conducted on the alpha diversity index. The between-group comparison of the relative abundance of gut microbiota taxa and the beta diversity were extracted and qualitatively analyzed.Results: Five studies were included involving 290 patients with IMN, 100 healthy controls (HCs), and 129 patients with diabetic kidney disease (DKD). The quantitative combination of alpha diversity indices indicated that although bacterial richness was impaired [ACE, SMD = 0.12, (−0.28, 0.52), p = 0.55, I2 = 0%; Chao1, SMD = −0.34, (−0.62, −0.06), p < 0.05, I2 = 36%], overall diversity was preserved [Shannon, SMD = −0.16, (−0.64, 0.31), p = 0.50, I2 = 53%; Simpson, SMD = 0.27, (−0.08, 0.61), p = 0.13, I2 = 0%]. The beta diversity was significantly varied compared to HCs or DKD patients. Compared to HCs, the abundance of Proteobacteria increased, while that of Firmicutes decreased at the phylum level. Furthermore, the abundance of Lachnospira were depleted, while those of Streptococcus were enriched at the genus level. Proteobacteria and Streptococcus were also increased compared to DKD patients.Conclusions: The expansion of Proteobacteria and depletion of Lachnospira may be critical features of the altered gut microbiota in patients with IMN. This condition may play an important role in the pathogenesis of IMN and could provide bacterial targets for diagnosis and therapy.

BackgroundEmerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis.MethodsTo characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis.ResultsThere were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis.ConclusionsFor the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.

Multiple myeloma (MM), an incurable hematological malignancy with clonal proliferation of plasma cells, is mainly characterized by excessive production of monoclonal immunoglobulins and free light chains (FLCs). Kidney injury is one of the main clinical manifestations and is also a significant predictor of the prognosis of symptomatic MM patients, especially those who require dialysis-supported treatment. Overproduction of FLCs is the trigger for kidney injury, as they can induce the transcription of inflammatory and profibrotic cytokines in the proximal tubule and bind to Tamm–Horsfall protein in the distal tubules to form casts that obstruct the tubules, leading to kidney injury and even renal fibrosis. In addition to traditional antimyeloma treatment, high-cutoff hemodialysis (HCO-HD), which can effectively remove FLCs in vitro, has attracted much attention in recent years. Due to its greater membrane pore size, it has significant advantages in removing larger molecules and can be applied in rhabdomyolysis, sepsis, and even myeloma cast nephropathy. However, mounting questions have recently been raised regarding whether HCO-HD can truly provide clinical benefits in MM patients with acute kidney injury (AKI). Therefore, in this study, we discussed the pathological causes of AKI secondary to MM and summarized the current situation of HCO-HD in MM patients compared with other available extracorporeal techniques. In addition, pivotal clinical trials that reflect the ability of the clearance of FLCs and the side effects of HCO-HD are highlighted, and the relevant protocol of HCO-HD is also provided to assist clinicians in decision-making.

Although patients with light chain amyloidosis (AL) may present with co-deposition of amyloid and immune complexes (ICs) in renal biopsies, data on clinical characteristics and prognostic value of renal IC deposition are limited. A total of 73 patients with AL amyloidosis who were newly diagnosed by renal biopsy in Xijing Hospital (Xi’an, China) were divided into two groups (IC and non-IC groups). As a result, renal IC deposition was found in 26% of patients. Patients with IC deposition were associated with more urinary protein excretion and lower serum albumin. Notably, patients in the non-IC group achieved higher hematological overall response rate (81.5% vs. 47.4%, p = 0.007) and ≥VGPR rate (75.9% vs. 39.8%, p = 0.004) compared with those in IC group. Renal response rate was also higher in the non-IC group (63% vs. 31.6%, p = 0.031). With the median follow-up time of 19 months, a significantly worse overall survival was observed in patients with the IC group as compared with those without renal IC deposition in the Kaplan–Meier analysis (p = 0.036). Further multivariate analysis demonstrated that renal immune complex deposition was associated with worse overall survival in patients with AL amyloidosis (HR 5.927, 95% CI 2.148–16.356, p = 0.001).

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.

Abstract 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

Background: To determine the safety and efficacy of corticosteroids (CS) combined with cyclophosphamide (CTX), compared with CS combined with mycophenolate mofetil (MMF) for IgA nephropathy (IgAN) patients with stage 3 and 4 CKD and proteinuria ≥1.0 g/24 h in a 10-year real-world study.Methods: We recruited 296 IgAN patients with renal insufficiency and proteinuria ≥1.0 g/24 h who received uncontrolled supportive care (USC) (n = 44), CS + CTX therapy (n = 164) and CS + MMF therapy (n = 88) in Xijing Hospital from July 2008 to December 2019. The combined event was defined as a ≥50% decrease in eGFR, ESRD, or death.Results: The median of the follow-up period was 39.3 months. One hundred and twenty-five patients experienced the combined event, 65.9, 37.8, and 38.6% in the USC, CS + CTX, and CS + MMF group, respectively. In multivariate Cox regression analyses, CS combined with CTX (HR = 0.457, 95% CI 0.238-0.878, p = 0.019) significantly reduced the incidence of the combined event, whereas CS + MMF (HR = 0.523, 95% CI 0.246-1.109, p = 0.091) did not reduce the risk of the combined event, compared with USC. The incidence of pneumonia and death due to infection in the CS + MMF group was higher than other two groups.Conclusion: Compared with USC and CS + MMF therapy, CS + CTX therapy was more safety and possibly more effective. The results need to be further confirmed by large randomized controlled studies.

BackgroundEmerging evidence indicates that gut dysbiosis is involved in the occurrence and development of diabetic kidney diseases (DKD). However, the key microbial taxa closely related to DKD have not been determined.MethodsPubMed, Web of Science, Cochrane, Chinese Biomedical Databases, China National Knowledge Internet, and Embase were searched for case-control or cross-sectional studies comparing the gut microbiota of patients with DKD and healthy controls (HC) from inception to February 8, 2022, and random/fixed-effects meta-analysis on the standardized mean difference (SMD) were performed for alpha diversity indexes between DKD and HC, and beta diversity indexes and the relative abundance of gut microbiota were extracted and summarized qualitatively.ResultsA total of 16 studies (578 patients with DKD and 444 HC) were included. Compared to HC, the bacterial richness of patients with DKD was significantly decreased, and the diversity indexes were decreased but not statistically, companying with a distinct beta diversity. The relative abundance of phylum Proteobacteria, Actinobacteria, and Bacteroidetes, family Coriobacteriaceae, Enterobacteriaceae, and Veillonellaceae, genus Enterococcus, Citrobacter, Escherichia, Klebsiella, Akkermansia, Sutterella, and Acinetobacter, and species E. coli were enriched while that of phylum Firmicutes, family Lachnospiraceae, genus Roseburia, Prevotella, and Bifidobacterium were depleted in patients with DKD.ConclusionsThe gut microbiota of patients with DKD may possess specific features characterized by expansion of genus Escherichia, Citrobacter, and Klebsiella, and depletion of Roseburia, which may contribute most to the alterations of their corresponding family and phylum taxa, as well as the bacterial diversity and composition. These microbial taxa may be closely related to DKD and serve as promising targets for the management of DKD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021289863.

Abstract Background Hyperbilirubinemia after heart valve surgery (HVS) with cardiopulmonary bypass is frequently observed and associated with worse outcomes. We investigated the characteristics and prognosis of patients with severe hyperbilirubinemia after HVS for rheumatic heart disease (RHD) to identify the clinical outcomes and potential risk factors. Methods Between 2015 and 2018, patients who underwent HVS in the cardiac surgery intensive care unit of our hospital were retrospectively screened. Risk factors for acute kidney injury (AKI), the requirement for continuous renal replacement therapy (CRRT), and in-hospital and long-term mortality were identified by univariate and multivariate analyses. The patient survival proportion was graphically presented with the Kaplan–Meier method. Results A total of 149 patients who underwent HVS for RHD and had severe postoperative hyperbilirubinemia were included. Of the included patients, 80.5% developed postoperative AKI, and 18.1% required CRRT. The in-hospital mortality was 30.2%. Backward logistic regression analysis showed that the time to peak TB concentration (odds ratio [OR] 1.557, 95% confidence interval [CI] 1.259–1.926; P

Abstract Background Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality. Methods We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained. Results The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4–25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e’, GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival. Conclusions STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.

Background Emerging evidence demonstrates that gut dysbiosis is implicated in the pathogenesis of chronic kidney disease (CKD) with underlying mechanisms involving mucosal and/or systematic immunity or metabolic disorders. However, the profile of gut microbiota in patients with CKD has not been completely explored. Methods Databases from their date of inception to 31 March 2020 were systematically searched for case-control or cross-sectional studies comparing the gut microbial profiles in adult patients with CKD or end-stage renal disease (ESRD) with those in healthy controls. Quantitative analysis of alterations in gut microbial profiles was conducted. Results Twenty-five studies with a total of 1436 CKD patients and 918 healthy controls were included. The present study supports the increased abundance of, phylum Proteobacteria and Fusobacteria, genus Escherichia_Shigella, Desulfovibrio, and Streptococcus, while lower abundance of genus Roseburia, Faecalibacterium, Pyramidobacter, Prevotellaceae_UCG-001, and Prevotella_9 in patients with CKD; and increased abundance of phylum Proteobacteria, and genus Streptococcus and Fusobacterium, while lower abundance of Prevotella, Coprococcus, Megamonas, and Faecalibacterium in patients with ESRD. Moreover, higher concentrations of trimethylamine-N-oxide and p-cresyl sulfate and lower concentrations of short-chain fatty acids were observed. Gut permeability in patients with CKD was not determined due to the heterogeneity of selected parameters. Conclusions Specific alterations of gut microbial parameters in patients with CKD were identified. However, a full picture of the gut microbiota could not be drawn from the data due to the differences in methodology, and qualitative and incomplete reporting of different studies.

Background Gut dysbiosis may be implicated in the pathogenesis of IgA nephropathy (IgAN) through immune and/or metabolite pathways. Fecal microbiota transplantation (FMT) could reestablish the micro-ecological balance in IgAN, although this has never been attempted before. We explored whether FMT could be efficacious in treating IgAN in two patients with refractory IgAN. Case presentation Two Chinese female patients with IgAN failed to achieve clinical remission after receiving several rounds of immunosuppressive therapy and suffered from unbearable adverse effects due to immunosuppressants. Both patients received intensive fresh FMT conducted through transendoscopic enteral tubing (TET) regularly for 6–7 months, and were followed up for a further 6 months. Partial clinical remission was achieved in both patients, evidenced by a decrease in the 24-h urinary protein (24-hUP) to less than half of baseline during FMT treatment or follow-up, along with increased serum albumin (sAlb) and stable kidney function. The gut microbiota of both patients was distorted with lower biodiversity and altered composition, which was reversed following FMT. Phylum Proteobacteria decreased while genus Prevotella increased during and after FMT. The intensive fresh FMT was well-tolerated, and no severe adverse events occurred. Conclusions Preliminary evidence of the safety and efficacy of FMT for treating refractory IgAN may provide a new direction by which to decipher the pathogenesis of IgAN.

Purpose Type B aortic dissection is a rare but life-threatening disease. Thoracic endovascular aortic repair (TEVAR) was widely used for Type B aortic dissection patients in the last decade due to the lower mortality and morbidity compared with open chest surgical repair (OCSR). AKI in type B aortic dissection is a well-recognized complication and indicates poor short-term and long-term outcome. The objective of this concise review was to identify the risk factors and the impact of AKI on type B aortic dissection patients. Methods and results A literature search was performed using PubMed, Embase, MEDLINE, and Cochrane Library with the search terms ‘type B aortic dissection’ and ‘acute kidney injury’ (AKI), and all English-language literatures published in print or available online from inception through August 2020 were thoroughly reviewed. Studies that reported relative AKI risks and outcomes in type B aortic dissection patient were included. Major mechanisms of AKI in type B aortic dissection included renal hypoperfusion, inflammation response, and the use of contrast medium. Type B aortic dissection patients with AKI significantly had increased hospital stay duration, need of renal replacement therapy, and 30-d and 1-year mortality. Conclusions AKI in type B aortic dissection is a well-recognized complication and associated with poor short-term and long-term outcome. Early identification of high-risk patients, early diagnosis of AKI, stabilization of the hemodynamic parameters, avoidance of nephrotoxic drugs, and optimization of the use of contrast agents are the major strategies for the reduction of AKI in type B aortic dissection patients.

Background It is debated whether patients with IgAN with heavy proteinuria and decreased eGFR benefit from aggressive treatment consisting of corticosteroids alone or combined with immunosuppressive agents. Methods A retrospective study was performed between January 2008 and December 2016 on patients with IgAN who had urinary protein excretion > 1.0 g/d and an eGFR between 15 and 59 mL/min/1.73 m2. These patients were assigned to receive supportive care alone or supportive care plus immunosuppressive therapy. The primary outcome was defined as the first occurrence of a 50% decrease in eGFR or the development of ESKD. Results All 208 included patients were followed for a median of 43 months, and 92 (44%) patients experienced the primary outcome. Cumulative kidney survival was better in the immunosuppression group than in the supportive care group (p

Due to rapid development of high-throughput sequencing and biotechnology, it has brought new opportunities and challenges in developing efficient computational methods for exploring personalized genomics data of cancer patients. Because of the high-dimension and small sample size characteristics of these personalized genomics data, it is difficult for excavating effective information by using traditional statistical methods. In the past few years, network control methods have been proposed to solve networked system with high-dimension and small sample size. Researchers have made progress in the design and optimization of network control principles. However, there are few studies comprehensively surveying network control methods to analyze the biomolecular network data of individual patients. To address this problem, here we comprehensively surveyed complex network control methods on personalized omics data for understanding tumor heterogeneity in precision medicine of individual patients with cancer.

ABSTRACT 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 2372 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 LPS 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.

BackgroundProbiotics, prebiotics, and synbiotics are three different supplements to treat end stage renal disease (ESRD) patients by targeting gut bacteria. The comprehensive comparison of the effectiveness of different supplements are lacking.ObjectivesThe purpose of this network meta-analysis (NMA) is to assess and rank the efficacy of probiotics, prebiotics, and synbiotics on inflammatory factors, uremic toxins, and gastrointestinal symptoms (GI symptoms) in ESRD patients undergoing dialysis.MethodsRandomized clinical trials were searched from the PubMed, Embase, and Cochrane Register of Controlled Trials databases, from their inception until 4 September 2021. Random-effect model were used to obtain all estimated outcomes in network meta-analysis (NMA). Effect estimates were presented as mean differences (Mean ± SD) with 95% confidence interval (CI). The comprehensive effects of all treatments were ranked by the surface under the cumulative ranking (SUCRA) probabilities.ResultsTwenty-five studies involved 1,106 participants were included. Prebiotics were superior in decreasing Interleukin-6 (IL-6; SMD –0.74, 95% CI [–1.32, –0.16]) and tumor-necrosis factor-α (TNF-α; SMD –0.59, 95% CI [–1.09, –0.08]), synbiotics were more effective in declining C-reactive protein (CRP; SMD –0.69, 95% CI [–1.14, –0.24]) and endotoxin (SMD –0.83, 95% CI [–1.38, –0.27]). Regarding uremic toxins, prebiotics ranked highest in reducing indoxyl sulfate (IS; SMD –0.43, 95% CI [–0.81, –0.05]), blood urea nitrogen (BUN; SMD –0.42, 95% CI [–0.78, –0.06]), and malondialdehyde (MDA; SMD –1.88, 95% CI [–3.02, –0.75]). Probiotics were rated as best in alleviating GI symptoms (SMD: –0.52, 95% CI [–0.93, –0.1]).ConclusionOur research indicated prebiotics were more effective in declining IL-6, TNF-α, IS, MDA, and BUN, synbiotics lowering CRP and endotoxin significantly, and probiotics were beneficial for alleviating GI symptoms, which may contribute to better clinical decisions. This study was registered in PROSPERO (Number: CRD42021277056).Systematic Review Registration[http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021277056].

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for the diagnosis of diabetic kidney disease (DKD), but its utility is currently debated. This meta-analysis aims to evaluate the diagnostic value of NGAL for DKD. Method: MEDLINE, Embase, ­Cochrane Library, CNKI, and CBM databases were searched up to April 13, 2019. In bivariate random-effect models, the diagnostic performance of NGAL for DKD was assessed using pooled estimates of sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and hierarchical summary receiver-operating characteristic analysis. Results: Nineteen studies were eligible for the meta-analysis. Serum NGAL had a pooled sensitivity and specificity of 0.79 (95% confidence intervals [CI] 0.60–0.91) and 0.87 (0.75–0.93) (7 studies, 1,238 patients). The pooled positive likelihood ratio (LR+) and negative likelihood ratio (LR–) were 5.97 (3.03–11.76) and 0.24 (0.11–0.51). For urine NGAL, the pooled sensitivity, specificity, LR+, and LR– were 0.85 (0.74–0.91), 0.74 (0.57–0.86), 3.26 (1.87–5.67), and 0.21 (0.12–0.35), respectively (10 studies, 1,369 patients). The pooled sensitivity and specificity for kidney disease in normoalbuminuric patients with diabetes was 0.90 (0.82–0.95) and 0.97 (0.90–0.99) for both serum NGAL and 0.94 (0.87–0.98) and 0.90 (0.81–0.96) for urine NGAL (4 studies, 221 patients). NGAL appeared to perform similarly in subgroup analysis. Conclusion: The meta-analysis has shown that NGAL may be useful for DKD classification and also has a potential diagnostic value for normoalbuminuric kidney disease. Large-scale prospective studies are required to clarify its role in the diagnosis and risk stratification of patients with DKD.

Abstract Background Hyperbilirubinemia is one of the common complications after cardiac surgery and is associated with increased mortality. However, to the best of our knowledge, the reports on clinical significance of postoperative severe hyperbilirubinemia in Stanford type A aortic dissection (AAD) patients were limited. Methods Patients who underwent surgical treatment for AAD in our center between January 2015 and December 2018 were retrospectively screened. In-hospital mortality, long-term mortality, acute kidney injury (AKI), and the requirement of continuous renal replacement therapy (CRRT) were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of these endpoints. Results After screening, 271 patients were included in our present study. Of the included patients, 222 (81.9%) experienced postoperative AKI, and 50 (18.5%) received CRRT. The in-hospital mortality was 30.3%. The 1-year, 2-year, and 3-year cumulative mortality were 32.9, 33.9, and 35.3%, respectively. Multivariate Logistic regression analysis indicated that age (P

Purpose We conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus those of low molecular weight heparin (LMWH) anticoagulation for CVVH in severe hypercalcemia patients. Methods Between January 2014 and May 2019, 33 severe hypercalcemia patients underwent CVVH. Patients were divided into the RCA and LMWH groups. Calcium-free replacement solution was used. Serum total calcium reduction rate (RRSeCa), filter lifespan, bleeding, totCa/ionCa ratio, citrate accumulation, and catheter occlusion were evaluated as outcomes. Results RCA and LMWH were employed for CVVH in 14 and 43 filters, respectively. RRSeCa was not significantly different between the LMWH and RCA groups (p = .320), but RCA-CVVH was more effective in reducing ionized calcium at half of the time points (p 72 h vs. 24.0 h [IQR, 15.0–26.0], p = .012). The incidence of filter failure was 55.8% (24/43) in the LMWH group and 21.4% (3/14) in the RCA group (p = .033). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (p = .043, 95% CI 0.059–0.957, HR = 0.238). No citrate accumulation or bleeding episodes were observed in the RCA-CVVH group. Seven bleeding episodes (7/43, 16.3%) occurred in the LMWH-CVVH group. Conclusions In patients with severe hypercalcemia who underwent CVVH, RCA more effectively decreased calcium levels and had a superior filter lifespan and no obvious adverse events compared with LMWH. Further prospective, randomized, controlled studies are warranted to obtain robust evidence.

Background: Circular RNAs (circRNAs), which have broad posttranscriptional regulatory potencies, are involved in the pathogenesis of fibrotic diseases and are promising diagnostic biomarkers and therapeutic targets. However, their specific roles in renal fibrosis remain elusive.Methods: A robust unilateral renal ischemia reperfusion injury (UIRI) mouse model was established to recapitulate the pathophysiology of renal fibrosis. The expression of circRNAs, miRNAs, and mRNAs was profiled by high-throughput RNA sequencing technology.Results: In total, 4983 circRNAs, 216 miRNAs, and 6371 mRNAs were differentially expressed in UIRI-induced fibrotic kidneys. Candidate circRNAs and miRNAs were validated by RT–qPCR in both UIRI and unilateral ureteral obstruction mouse models. Bioinformatic analysis indicated that the parental genes of the differentially expressed circRNAs were predominantly implicated in focal adhesion, adhesion junctions, and regulation of actin cytoskeleton pathways. Through circRNA-miRNA-mRNA construction, we identified two hub genes, circSlc8a1 and circApoe, that targeted a large number of differentially expressed miRNAs and mRNAs related to metabolism and cytokine–cytokine receptor pathways, respectively.Conclusion: CircRNAs were dysregulated in the UIRI model and might be potentially involved in the pathogenesis of renal fibrosis. Research efforts should focus on unravelling the functions of aberrantly expressed circRNAs in renal fibrosis to uncover biomarkers that would enable early diagnosis and the design of prompt therapeutic interventions to prevent disease progression.

Objective: To determine whether there is an association between microhematuria and relapse or kidney disease progression in patients with primary membranous nephropathy (PMN).Methods: A cohort of 639 patients with biopsy-proven PMN from two centers was followed for a median of 40 months. The exposures were initial hematuria, time-averaged hematuria, and cumulative duration of hematuria. The outcomes were relapse and renal progression, which were defined by a 40% reduction in renal function or end-stage renal disease. Cox proportional hazards regression and competing risk analyses were performed to yield hazard ratios (HRs) and subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs). Sensitivity and interaction analyses were also performed.Results: After adjusting for confounders, a higher level of initial hematuria was associated with a 1.43 (95% CI, 1.15–1.78) greater hazard of relapse. Worsening hematuria remarkably increased the risk of short-term relapse (HR, 4.64; 3.29–6.54). Time-averaged hematuria (sHR, 1.35; 1.12–1.63) and cumulative duration of hematuria (sHR, 1.17; 1.02–1.34) were independent predictors of renal progression. Hematuria remission was related to a reduced risk of renal progression over time in patients with positive microhematuria (sHR, 0.63; 0.41–0.96).Conclusions: A higher level of initial hematuria was a remarkable predictor of relapse in patients with PMN, and the magnitude and persistence of microhematuria were independently associated with kidney disease progression.

Background: Catheter malfunction is a common complication of peritoneal dialysis (PD). This study aimed to retrospectively analyze the risk factors and management of catheter malfunction in urgent-start PD.Methods: Patients who underwent urgent-start PD were divided into catheter-malfunction and control groups. Baseline demographic and laboratory data of the two groups were compared, and the risk factors for catheter malfunction were analyzed. Primary outcome measure was catheter survival, and the secondary outcomes were surgical complications and malfunction treatment.Results: Total of 700 patients was analyzed, among whom 143 (20.4%) experienced catheter malfunctions, specifically catheter migration (96, 67.1%), omental wrapping (36, 25.2%), and migration plus omental wrapping (11, 7.7%). Catheter survival time in the malfunction group (202.5 ± 479.4 days) was significantly shorter than that in the control group (1295.3 ± 637.0 days) (P < 0.001). Multivariate analysis revealed higher body mass index [hazard ratio (HR), 1.061; 95% confidence intervals (CI), 1.010–1.115; P = 0.018], lower surgeon count (HR, 1.083; 95% CI, 1.032–1.136; P = 0.001), and higher serum potassium (HR, 1.231; 95% CI, 1.041–1.494; P = 0.036) as independent risk factors for catheter malfunction, while older age (HR, 0.976, 95% CI, 0.962–0.991; P = 0.002) and colonic dialysis (HR, 0.384; 95% CI, 0.254–0.581; P < 0.001) as protective factors. Further subgroup analysis revealed a shorter catheter survival time in patients with younger age ( ≤ 40 years), higher serum potassium levels (≥5 mmol/L), while a longer catheter survival time in patients with colonic dialysis. PD tube and subcutaneous tunnel preservation was successful in 41 out of 44 patients with omental wrapping. All patients had good post-incision prognoses.Conclusions: Urgent-start PD is safe and effective for unplanned PD patients. Adequate pre-operative colonic dialysis and serum potassium level control are conducive in preventing catheter malfunction. Conservative treatment is effective in managing catheter migration alone, while preservation of the PD tube and the subcutaneous tunnel is effective for omental wrapping.

Abstract Background Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients. Methods We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review. Results After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD − 65.82 [− 194.19, 62.55]), lactate (MD 0.49 [− 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [− 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD − 0.04 [− 0.13, 0.05]), serum lactate level (MD 0.69 [− 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [− 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h. Conclusions Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.

The pathogenesis of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) is characterized by immune dysregulation, which is related to gut dysbiosis. The aim of the study was to compare the gut microbiota of patients with IgAN and MN vs. healthy controls. We used 16S rDNA amplicon sequencing to investigate the bacterial communities of 44 patients with kidney biopsy-proven IgAN, 40 patients with kidney biopsy-proven MN, and 30 matched healthy controls (HC). The abundance of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis were significantly higher in IgAN than in HC, whereas lower abundances were observed for Roseburia, Lachnospiraceae_unclassified, Clostridium_sensu_stricto_1, and Fusobacterium. Furthermore, the abundance of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis, Streptococcus, and Enterobacteriaceae_unclassified increased, while that of Lachnospira, Lachnospiraceae_unclassified, Clostridium_sensu_stricto_1, and Veillonella decreased in MN. The abundance of Megasphaera and Bilophila was higher, whereas that of Megamonas, Veillonella, Klebsiella, and Streptococcus was lower in patients with IgAN than in those with MN. Analysis of the correlations showed that in the IgAN group, Prevotella was positively correlated, while Klebsiella, Citrobacter, and Fusobacterium were negatively correlated with the level of serum albumin. Positive correlation also existed between Bilophila and Crescents in the Oxford classification of IgAN. In the MN group, negative correlation was observed between Escherichia-Shigella and proteinuria, Bacteroides and Klebsiella showed positive correlation with the MN stage. Patients with IgAN and MN exhibited gut microbial signatures distinct from healthy controls. Our study suggests the potential of gut microbiota as specific biomarker and contributor in the pathogenesis of IgAN and MN.

OBJECTIVE:There are controversial opinions on anticoagulation for continuous venovenous hemofiltration (CVVH) in patients with liver failure (LF) and increased bleeding risk. Therefore, we conducted a retrospective study to evaluate the efficacy and safety of regional citrate anticoagulation (RCA) versus no-anticoagulation for CVVH in these patients. METHODS:The included patients were divided into RCA and no-anticoagulation group according to the CVVH anticoagulation strategy they accepted for CVVH. Filter lifespan, bleeding, citrate accumulation, catheter occlusion, and totCa/ionCa ratio were evaluated as outcomes. RESULTS:In the original cohort, the filter lifespan of the RCA group (41 patients, 79 filters) was significantly longer than the no-anticoagulation group (62 patients, 162 filters) (> 72 hours vs 39.5 hours (IQR 31.2-47.8), P = 0.002). The adjusted results demonstrated that RCA could significantly reduce the risk of filter failure (HR = 0.459, 95%CI 0.26-0.82, P = 0.008). Four episodes of totCa/ionCa > 2.5 were observed in the RCA group and continuously accepted RCA-CVVH after the reduction of citrate dose and blood flow. No obvious citrate accumulation was observed in these patients. In the matched cohort, the filter lifespan of the RCA group was significantly longer than the no-anticoagulation group (P = 0.013) as well. No significant difference in the episodes of totCa/ionCa > 2.5 was observed between the two matched groups (P = 0.074). Both in the original cohort and the matched cohort, the bleeding, acidosis, alkalosis, and catheter occlusion incidences were not significantly different between the two groups. CONCLUSIONS:In LF patients with increased bleeding risk who underwent CVVH, RCA could prolong the filter lifespan and be safely used with careful blood gas monitoring and citrate dose adjusting. Further prospective, randomized, control studies are warranted to obtain robust evidences.

BACKGROUND AND OBJECTIVES: The evidence for high-volume hemofiltration plus hemoperfusion (HVHF&HP) for hyperlipidemic severe acute pancreatitis (HL-SAP) is anecdotal. The purpose of our study was to evaluate the efficacy of HVHF&HP for HL-SAP in a prospective controlled study. DESIGN AND SETTING: Prospective controlled pilot study between May 2010 and May 2013 in a hospital intensive care unit. PATIENTS AND METHODS: HL-SAP patients chose conventional treatment alone (the control group) or conventional treatment combined with the experimental protocol (the HVHF&HP group) and were prospectively followed in our hospital. APACHE II score, SOFA score, ICU and hospital stay duration, and serum biomarkers were considered endpoints. RESULTS: Ten HL-SAP patients accepted conventional treatment alone (the control group) and 10 patients underwent HVHF&HP combined with conventional treatment (the HVHF&HP group). The APACHE II score, SOFA score, systolic blood pressure, diastolic blood pressure, heart rate, serum amylase, and serum creatinine were significantly reduced after the HVHF&HP treatment. The changes in these variables were significantly different between the HVHF&HP and control group at 48 hours after the initiation of treatment. Patients in the HVHF&HP group had a significantly shorter ICU stay (P=.015). The reduction in serum triglyceride and cholesterol in the HVHF&HP group after 2, 6, 12, 24, and 48 hours was greater than the control group. All of the tested serum cytokines were significantly decreased after HVHF&HP treatment (P

BACKGROUND: Epithelial-to-Mesenchymal Transition (EMT) induced by glucose in human peritoneal mesothelial cells (HPMCs) is a major cause of peritoneal membrane (PM) fibrosis and dysfunction. METHODS: To investigate serum response factor (SRF) impacts on EMT-derived fibrosis in PM, we isolated HPMCs from the effluents of patients with end-stage renal disease (ESRD) to analyze alterations during peritoneal dialysis (PD) and observe the response of PM to SRF in a rat model. RESULTS: Our results demonstrated the activation and translocation of SRF into the nuclei of HPMCs under extensive periods of PD. Accordingly, HPMCs lost their epithelial morphology with a decrease in E-cadherin expression and an increase in α-smooth muscle actin (α-SMA) expression, implying a transition in phenotype. PD with 4.25% glucose solution significantly induced SRF up-regulation and increased peritoneal thickness. In immortal HPMCs, high glucose (HG, 60 mmol/L) stimulated SRF overexpression in transformed fibroblastic HPMCs. SRF-siRNA preserved HPMC morphology, while transfection of SRF plasmid into HPMCs caused the opposite effects. Evidence from electrophoretic mobility shift, chromatin immunoprecipitation and reporter assays further supported that SRF transcriptionally regulated Snail, a potent inducer of EMT, by directly binding to its promoter. CONCLUSIONS: Our data suggested that activation of SRF/Snail pathway might contribute to the progressive PM fibrosis during PD.

Hypoxia-induced renal tubular cell epithelial-mesenchymal transition (EMT) is an important event leading to renal fibrosis. MicroRNAs (miRNAs) are small non-coding RNA molecules that bind to their mRNA targets, thereby leading to translational repression. The role of miRNA in hypoxia-induced EMT is largely unknown.miRNA profiling was performed for the identification of differentially expressed miRNAs in HK-2 cells under normal and low oxygen, and the results were then verified by quantitative real time RT-PCR (qRT-PCR). The function of miRNAs in hypoxia-induced renal tubular cell EMT was assessed by the transfection of specific miRNA inhibitors and mimics. Luciferase reporter gene assays and western blot analysis were performed to validate the target genes of miR-34a. siRNA against Jagged1 was designed to investigate the role of the miR-34a-Notch pathway in hypoxia induced renal tubular cell EMT. miRNA-34a was identified as being downregulated in hypoxic renal tubular epithelial cells. Inhibition of miR-34a expression in HK-2 cells, which highly express endogenous miR-34a, promoted a mesenchymal phenotype accompanied by reduced expression of the epithelial marker Z0-1, E-cadherin and increased expression of the mesenchymal markers α-SMA and vimentin. Conversely, miR-34a mimics effectively prevented hypoxia-induced EMT. Transfection of miRNA-34a in HK-2 cells under hypoxia abolished hypoxia-induced expression of Notch1 and Jagged1 as well as Notch downstream signals, such as snail. Western blot analysis and luciferase reporter gene assays showed direct evidence for miR-34a targeting Notch1 and Jagged1. siRNAs against Jagged1 or Notch1 effectively prevented miR-34a inhibitor-induced tubular epithelial cell EMT.Our study provides evidence that the hypoxia-induced decrease of miR-34a expression could promote EMT in renal tubular epithelial cells by directly targeting Notch1 and Jagged1, and subsequently, Notch downstream signaling.

Here we presented that the expression of RUNX3 was significantly decreased in 75 cases of clear cell renal cell carcinoma (CCRCC) tissues (p

Calcyclin-binding protein (CacyBP/SIP), identified on the basis of its ability to interact with S100 proteins in a calcium-dependent manner, was previously found to inhibit the proliferation and tumorigenesis of gastric cancer cells in our laboratory. Importantly, the effects of S100 proteins on the biological behavior of CacyBP/SIP in gastric cancer remain unclear. Herein, we report the construction of eukaryotic expression vectors for wild-type CacyBP/SIP and a truncated mutant lacking the S100 protein binding domain (CacyBP/SIPΔS100). The expressions of the wild-type and truncated recombinant proteins were demonstrated by transfection of MKN45 gastric cancer cells. Co-immunoprecipitation assays demonstrated interaction between S100A6 and wild-type CacyBP/SIP in MKN45 cells. Removal of the S100 protein binding domain dramatically reduced the affinity of CacyBP/SIP for S100 proteins as indicated by reduced co-immunoprecipitation of S100A6 by CacyBP/SIPΔS100. The MTT assay, FACS assay, clonogenic assay and tumor xenograft experiment were performed to assess the effect of CacyBP/SIP on cell growth and tumorigenesis in vitro and in vivo. Overexpression of CacyBP/SIP inhibited the proliferation and tumorigenesis of MKN45 gastric cancer cells; the proliferation and tumorigenesis rates were even further reduced by the expression of CacyBP/SIPΔS100. We also showed that S100 proteins negatively regulate CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation, through an effect on β-catenin protein expression and transcriptional activation of Tcf/LEF. Although the underlying mechanism of action requires further investigation, this study provides new insight into the interaction between S100 proteins and CacyBP/SIP, which might enrich our knowledge of S100 proteins and be helpful for our understanding of the development of gastric cancer.

MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.

Background: Monthly intravenous cyclophosphamide (IVCY) is a widely accepted induction therapy for lupus nephritis (LN) because this regimen balances the time needed for renal remission with the risk of adverse events. However, IVCY is associated with numerous severe toxicities. Mizoribine (MZR) was originally used as an antibiotic against Candida albicans, but researchers found it had strong immunosuppressive activity in various animal models. Previous clinical trials also examined the efficacy of MZR as an immunosuppressant, and it has been used for treatment of LN in Japan since 1990. We will conduct a phase 3 study in China to evaluate the efficacy and safety of oral MZR in comparison with standard IVCY in patients with LN. Methods: This study will be a multi-center, randomized, controlled, open-label clinical trial that consists of a screening period (seven days) followed by a treatment period (52 weeks). After screening, all eligible subjects will be randomized to an MZR or IVCY group in a 1:1 ratio. Then, subjects will initially receive methylprednisolone pulse therapy (0.5 g/day) for three days, followed by the study drug (MZR or CY) with oral corticosteroid therapy from visit two (day four). The efficacy and safety of oral MZR in comparison with standard IVCY will be determined. Discussion: This paper describes the protocol of a multi-center, open-label, randomized controlled trial that compares the efficacy and safety of MZR with IVCY for treatment of LN. The results may help determine whether LN should be considered an indication for this drug in China. Trial registration: ClinicalTrials.gov register, NCT02256150. Registered 2014-10-01. The protocol version number is 1.3 (2016-08-30).