Advancing precision medicine in immunoglobulin light-chain amyloidosis: a novel prognostic model incorporating multi-organ indicators.

To develop a more accurate prognostic model that incorporates indicators of multi-organ involvement for immunoglobulin light-chain (AL) Amyloidosis patients. Biopsy-proven AL amyloidosis patients between January 1, 2012, and February 28, 2023, were enrolled and randomly divided into a training set and a test set at a ratio of 7:3. Prognostic indicators that comprehensively cover cardiac, renal, and hepatic involvement were identified in the training set by random survival forest (RSF). Then, RSF and Cox models were established. The Concordance index (C-index) and integrated brier scores (IBS) were applied to evaluate the models' performance in the test set. Besides, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. A total of 173 eligible patients were included. After a median follow-up of 25.9 (9.2, 50.3) months, 48 (27.7%) patients died. Creatine kinase-MB, estimated glomerular filtration rate ≤ 50 mL/min/1.73 m2, interventricular septum ≥ 15 mm, ejection fraction, alanine aminotransferase and Live involved were selected to develop prediction models. The RSF model based on the above indicators achieved C-index and IBS values of 0.834 (95% CI 0.725-0.915) and 0.151 (95% CI 0.1402-0.181), respectively. At last, the NRI and IDI of the RSF model were 0.301 (95% CI 0.048-0.546, P = 0.012) and 0.157 (95% CI 0.041-0.269, P < 0.001) at 5-year by comparing the RSF model with the Cox model which is based on the Mayo 2012 staging system. The RSF model that incorporates indicators of multi-organ involvement had a great performance, which may be helpful for physicians' decision-making and more accurate overall survival prediction.

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.

Comparison of different peritoneal dialysis catheters on complication and catheter survival: A network meta-analysis of randomised controlled trials.

BACKGROUND: This network meta-analysis (NMA) aimed to compare the clinical advantage of four commonly used peritoneal dialysis catheters (PDCs) including the Swan neck segment with straight tip (Swan neck + S), Tenckhoff segment with straight tip (Tenckhoff + S), Swan neck segment with coiled tip (Swan neck + C) and Tenckhoff segment with coiled tip (Tenckhoff + C). METHODS: Randomised clinical trials were searched from PubMed, Embase, the Cochrane Register of clinical trials, China National Knowledge Infrastructure (CNKI) and ChinaInfo from their inception until July 31, 2022. Meta-analysis was performed using Stata 14.0 and RevMan 5.3.5 software to evaluate the four commonly used PDCs. RESULTS: Seventeen studies involved 1578 participants were included. NMA showed that compared with Swan neck + C, Swan neck + S significantly reduced catheter tip migration (OR 0.47 95% CI 0.22-0.99). Tenckhoff + S was more effective in reducing catheter dysfunction (OR 0.42, 95% CI 0.23-0.79), catheter tip migration with dysfunction (OR 0.19, 95% CI 0.05-0.78) and catheter removal (OR 0.56, 95% CI 0.34-0.93) which were consistent with the pairwise meta-analysis. According to the surface under the cumulative ranking curve, Swan neck + S emerged as the best PDC in the reduction of catheter tip migration (83.3%), followed by Tenckhoff + S (79.4%). Moreover, Tenckhoff + S (86.5%, 76.3%) and Swan neck + S (72.3, 86.9%) ranked as the first and second PDC for 1 and 2-year technique survival which was significantly higher than those of the other two PDCs. CONCLUSION: Our NMA showed Swan neck + S and Tenckhoff + S tended to be more efficacious than Swan neck + C and Tenckhoff + C in lowering the mechanical dysfunction and prolonging the technique survival, which may contribute to better clinical decisions. More randomised controlled trials with larger scales and higher quality are needed in order to obtain more credible evidence.

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy.

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.

The protective mechanism of SIRT3 and potential therapy in acute kidney injury.

Acute kidney injury (AKI) is a complex clinical syndrome with a poor short-term prognosis, which increases the risk of the development of chronic kidney diseases and end-stage kidney disease. However, the underlying mechanism of AKI remains to be fully elucidated, and effective prevention and therapeutic strategies are still lacking. Given the enormous energy requirements for filtration and absorption, the kidneys are rich in mitochondria, which are unsurprisingly involved in the onset or progression of AKI. Accumulating evidence has recently documented that Sirtuin 3 (SIRT3), one of the most prominent deacetylases highly expressed in the mitochondria, exerts a protective effect on AKI. SIRT3 protects against AKI by regulating energy metabolism, inhibiting oxidative stress, suppressing inflammation, ameliorating apoptosis, inhibiting early-stage fibrosis and maintaining mitochondrial homeostasis. Besides, a number of SIRT3 activators have exhibited renoprotective properties both in animal models and in vitro experiments, but have not yet been applied to clinical practice, indicating a promising therapeutic approach. In this review, we unravel and summarize the recent advances in SIRT3 research and the potential therapy of SIRT3 activators in AKI.

Risk factors for mortality in brain injury patients who have severe hypernatremia and received continuous venovenous hemofiltration.

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.

Regional Citrate Anticoagulation versus No Anticoagulation for CKRT in Patients with Liver Failure with Increased Bleeding Risk.

BACKGROUND: The opinions on the efficacy and safety of no anticoagulation versus regional citrate anticoagulation for continuous KRT (CKRT) were controversial in patients with severe liver failure with a higher bleeding risk. We performed a randomized controlled trial to assess no anticoagulation versus regional citrate anticoagulation for CKRT in these patients. METHODS: Adult patients with liver failure with a higher bleeding risk who required CKRT were considered candidates. The included participants were randomized to receive regional citrate anticoagulation or no-anticoagulation CKRT. The primary end point was filter failure. RESULTS: Of the included participants, 44 and 45 were randomized to receive regional citrate anticoagulation and no-anticoagulation CKRT, respectively. The no-anticoagulation group had a significantly higher filter failure rate (25 [56%] versus 12 [27%], P = 0.003), which was confirmed by cumulative incidence function analysis and sensitive analysis including only the first CKRT sessions. In the cumulative incidence function analysis, the cumulative filter failure rates at 24, 48, and 72 hours of the no-anticoagulation and regional citrate anticoagulation groups were 31%, 58%, and 76% and 11%, 23%, and 35%, respectively. Participants in the regional citrate anticoagulation group had significantly higher incidences of Ca 2+tot /Ca 2+ion >2.5 (7% versus 57%, P < 0.001), hypocalcemia (51% versus 82%, P = 0.002), and severe hypocalcemia (13% versus 77%, P < 0.001). However, most (73%) of the increased Ca 2+tot /Ca 2+ion ratios were normalized after the upregulation of the calcium substitution rate. In the regional citrate anticoagulation group, there was no significant additional increase in the systemic citrate concentration after 6 hours. CONCLUSIONS: For patients with liver failure with a higher bleeding risk who required CKRT, regional citrate anticoagulation resulted in significantly longer filter lifespan than no anticoagulation. However, regional citrate anticoagulation in patients with liver failure was associated with a significantly higher risk of hypocalcemia, severe hypocalcemia, and Ca 2+tot /Ca 2+ion >2.5. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: RCA for CRRT in Liver Failure and High Risk Bleeding Patients, NCT03791190 .

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.

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.

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.

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.

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.

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.

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.

Erratum: Twist1 downregulation of PGC-1α decreases fatty acid oxidation in tubular epithelial cells, leading to kidney fibrosis: Erratum.

[This corrects the article DOI: 10.7150/thno.71722.].

Downregulation of fatty acid oxidation led by Hilpda increases G2/M arrest/delay-induced kidney fibrosis.

Hypoxia-regulated proximal tubular epithelial cells (PTCs) G2/M phase arrest/delay was involved in production of renal tubulointerstitial fibrosis (TIF). TIF is a common pathological manifestation of progression in patients with chronic kidney disease (CKD), and is often accompanied by lipid accumulation in renal tubules. However, cause-effect relationship between hypoxia-inducible lipid droplet-associated protein (Hilpda), lipid accumulation, G2/M phase arrest/delay and TIF remains unclear. Here we found that overexpression of Hilpda downregulated adipose triglyceride lipase (ATGL) promoted triglyceride overload in the form of lipid accumulation, leading to defective fatty acid ß-oxidation (FAO), ATP depletion in a human PTC cell line (HK-2) under hypoxia and in mice kidney tissue treated with unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI). Hilpda-induced lipid accumulation caused mitochondrial dysfunction, enhanced expression of profibrogenic factors TGF-ß1, α-SMA and Collagen I elevation, and reduced expression of G2/M phase-associated gene CDK1, as well as increased CyclinB1/D1 ratio, resulted in G2/M phase arrest/delay and profibrogenic phenotypes. Hilpda deficiency in HK-2 cell and kidney of mice with UUO had sustained expression of ATGL and CDK1 and reduced expression of TGF-ß1, Collagen I and CyclinB1/D1 ratio, resulting in the amelioration of lipid accumulation and G2/M arrest/delay and subsequent TIF. Expression of Hilpda correlated with lipid accumulation, was positively associated with tubulointerstitial fibrosis in tissue samples from patients with CKD. Our findings suggest that Hilpda deranges fatty acid metabolism in PTCs, which leads to G2/M phase arrest/delay and upregulation of profibrogenic factors, and consequently promote TIF which possibly underlie pathogenesis of CKD.

Distribution of pathological types and epidemiological characteristics based on kidney biopsy in Northwest China.

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.

[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.

Diagnosis and treatment of brain injury complicated by hypernatremia.

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.