Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

Risk factors for repeated percutaneous transluminal angioplasty of hemodialysis vascular access after initial intervention.

BACKGROUND/AIMS: Percutaneous transluminal angioplasty (PTA) is a significant intervention to deal with occlusion and stenosis of vascular access. The study aimed to explore the risk factors of repeated PTA (re-PTA) after the initial intervention in patients undergoing hemodialysis. METHODS: This retrospective study included 180 patients who underwent successful PTA for the first time between March 2016 and December 2020. Information on demographic, clinical, anatomical, and medication variables was collected. Survival curves were plotted using Kaplan-Meier analysis and the risk factors associated with re-PTA were analyzed using univariate and multivariate Cox proportional hazards analyses. RESULTS: The primary clinical patency rates at 6, 12, and 24 months after PTA were found to be 85.2%, 70.7%, and 58.6%, respectively. The univariate Cox proportion hazards analysis revealed the association of non-antiplatelet agents (HR 2.368 95% CI 1.351 to 4.150, p = .003) and arteriovenous graft (AVG) (HR 2.096 95% CI 1.147 to 3.831, p = .016) with re-PTA. However, only non-antiplatelet therapy showed statistical significance (HR 2.368 95% CI 1.351 to 4.150, p = .003) in multivariate Cox proportional hazards analysis. CONCLUSIONS: Among the patients undergoing hemodialysis, the use of antiplatelet agents was associated with a lower risk of re-PTA. Therefore, the use of antiplatelet drugs may reduce the rates of re-PTA and help in maintaining the patency of vascular access.

Using intravoxel incoherent motion imaging to evaluate uric acid-induced renal injury and efficacy after treatment.

OBJECTIVES: To validate the feasibility of intravoxel incoherent motion imaging (IVIM) for monitoring renal injury and uric acid-lowering efficacy in a rat model of hyperuricaemia. METHODS: A total of 92 rats were analysed and categorized into 4 groups: control (CON), hyperuricaemia (HUA), allopurinol intervention (ALL), and combined intervention (COM). Eight rats were randomly selected from each group and underwent IVIM scanning on days 0, 1, 3, 5, 7, and 9. Quantitative magnetic resonance values (D, D*, and f values) measured from the different renal anatomical regions. Quantitative histopathological analysis was performed to assess renal tubular injury using neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis using alpha-smooth-muscle-actin (α-SMA). Pearson's correlation analysis was used to determine the correlation between IVIM-derived parameters and the expression of NGAL and α-SMA. RESULTS: The D values of the HUA, ALL, and COM groups generally showed a downward trend over time, and this fluctuation was most significant in the HUA group. The D values showed significant intergroup differences at each point, whereas only a few discrepancies were found in the D* and f values. In addition, the renal D value was negatively correlated with the positive staining rates for NGAL and α-SMA (P < .05), except for the lack of correlation between Dos and α-SMA (P > .05). CONCLUSION: IVIM could be a noninvasive and potential assessment modality for the evaluation of renal injury induced by hyperuricaemia and its prognostic efficacy. ADVANCES IN KNOWLEDGE: IVIM could be a surrogate manner in monitoring renal damage induced by hyperuricaemia and its treatment evaluation.

Emerging Therapeutic Approaches Targeting Ferroptosis in Cancer: Focus on Immunotherapy and Nanotechnology.

Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.

Correlation of Serum FGF23 and Chronic Kidney Disease-Mineral and Bone Abnormality Markers With Cardiac Structure Changes in Maintenance Hemodialysis Patients.

Background: CKD-MBD is a mineral and bone metabolism syndrome caused by chronic kidney disease. FGF23 is an important factor regulating phosphorus and is the main influencer in the CKD-MBD process. In this study, we observed the correlation among serum FGF23 and calcium, phosphorus and parathyroid hormone, and the correlation between FGF23 levels and cardiac structural changes in MHD patients. Methods: We examined serum FGF23 concentrations in 107 cases of MHD patients using the ELISA method, recorded demographic information and biochemical data, and analyzed the correlation between serum FGF23 levels and blood calcium and blood phosphorus and PTH levels. All patients were evaluated by cardiac color ultrasound, and we finally analyzed the association between the FGF23 level and cardiac structural changes. Results: In 107 cases of MHD patients, serum FGF23 levels were linearly associated with serum calcium (r = 0.27 P < 0.01) and parathyroid hormone levels (r = 0.25, P < 0.05). FGF 23 was negatively correlated with age (r = -0.44, P < 0.01).Serum FGF23 levels were correlated with right atrial hypertrophy in HD patients (P < 0.05). No correlation was found among FGF23, left ventricular hypertrophy/enlargement, and valve calcification stenosis (P > 0.05). Conclusion: Serum FGF23 showed a positive correlation among blood calcium levels and PTH levels in hemodialysis patients, and FGF23 levels can affect the incidence of right atrial hypertrophy in MHD patients.

A nomogram for predicting the mortality of patients with type 2 diabetes mellitus complicated with acute kidney injury in the intensive care unit.

BACKGROUND: There is no predictive tool for type 2 diabetes mellitus (T2DM) patients with acute kidney injury (AKI). Our study aimed to establish an effective nomogram model for predicting mortality in T2DM patients with AKI. METHOD: Data on T2DM patients with AKI were obtained from the Medical Information Mart for Intensive Care III. 70% and 30% of the patients were randomly selected as the training and validation cohorts, respectively. Univariate and multivariate logistic regression analyses were used to identify factors associated with death in T2DM patients with AKI. Factors significantly associated with survival outcomes were used to construct a nomogram predicting 90-day mortality. The nomogram effect was evaluated by receiver operating characteristic curve analysis, Hosmer‒Lemeshow test, calibration curve, and decision curve analysis (DCA). RESULTS: There were 4375 patients in the training cohort and 1879 in the validation cohort. Multivariate logistic regression analysis showed that age, BMI, chronic heart failure, coronary artery disease, malignancy, stages of AKI, white blood cell count, blood urea nitrogen, arterial partial pressure of oxygen and partial thromboplastin time were independent predictors of patient survival. The results showed that the nomogram had a higher area under the curve value than the sequential organ failure assessment score and simplified acute physiology score II. The Hosmer‒Lemeshow test and calibration curve suggested that the nomogram had a good calibration effect. The DCA curve showed that the nomogram model had good clinical application value. CONCLUSION: The nomogram model accurately predicted 90-day mortality in T2DM patients with AKI. It may provide assistance for clinical decision-making and treatment, thereby reducing the medical burden.

Cost-effectiveness analysis of autogenous arteriovenous fistula, arteriovenous graft, and tunneled-cuffed catheter for hemodialysis in patients with end-stage kidney disease in Southern China.

OBJECTIVES: To evaluate the cost-effectiveness of three permanent vascular accesses for maintenance hemodialysis patients from a hospital perspective throughout 5 years, which is the average life expectancy of patients with end-stage kidney disease. SUBJECTS AND METHODS: We conducted a EuroQol(EQ-5D) questionnaire survey between January 2021 and March 2021 with 250 patients to estimate the health utility of various states in patients under different hemodialysis vascular access. We designed a Markov model and conducted a cost-effectiveness analysis to compare the cost-effectiveness of three hemodialysis vascular access in Guangzhou throughout 5 years. RESULTS: The mean costs were US$44,481 with tunneled-cuffed catheter (TCC), and US$68,952 and US$59,247 with arteriovenous graft (AVG) and autogenous arteriovenous fistula (AVF), respectively. The mean quality-adjusted life-years (QALYs) was 1.41 with TCC, and 2.37 and 2.73 with AVG and AVF, respectively. AVG had an incremental cost-effectiveness ratio (ICER) of US$25,491 per QALY over TCC; AVF had an ICER of -US$26,958 per QALY over AVG. At a willingness to pay below US$10,633.8 per QALY, TCC is likely the most cost-effective vascular access. At any willingness to pay between US$10,633.8 and US$30,901.4 per QALY, AVF is likely the most cost-effective vascular access. CONCLUSION: These findings illustrate the value of AVF given its relative cost-effectiveness to other hemodialysis modalities. Although AVG costs much more than TCC for slightly higher QALYs than TCC, AVG still has a greater advantage over TCC for patients with longer life expectancy due to its lower probability of death.

Global Proteomic Analyses Reveals Abnormal Immune Regulation in Patients With New Onset Ankylosing Spondylitis.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients. Material and Methods: Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis. Results: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients. Conclusion: The key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS.

Syndrome of uremic encephalopathy and bilateral basal ganglia lesions in non-diabetic hemodialysis patient: a case report.

BACKGROUND: Uremic encephalopathy (UE), a toxic metabolic encephalopathy, is an uncommon complication resulting from endogenous uremic toxins in patients with severe renal failure. UE syndrome can range from mild inattention to coma. The imaging findings of UE include cortical or subcortical involvement, basal ganglia involvement and white matter involvement. The basal ganglia type is uncommon, although previous cases have reported that Asian patients with diabetes mellitus (DM) are usually affected. CASE PRESENTATION: A 32 year-old woman with a history of non-diabetic hemodialysis for 3 years suffered from severe involuntary movement, and brain magnetic resonance imaging showed symmetrical T2-weighted imaging (T2WI) and T2/fluid-attenuated inversion recovery (T2FLAIR) hyperintense nonhemorrhagic lesions in the bilateral basal ganglia. She was diagnosed with UE as syndrome of bilateral basal ganglia lesions, due to a combined effect of uremic toxins and hyperthyroidism. After treatment with high frequency and high flux dialysis, hyperbaric oxygen therapy and declining parathyroid hormone, the patient achieved complete remission with normal body movement and was discharged. CONCLUSION: UE with basal ganglia involvement is uncommon, although generally seen in Asian patients with DM. Our case reported a hemodialysis patient that had non-diabetic UE with typical bilateral basal ganglia lesions, presenting with involuntary movement.