NET-Related Gene as Potential Diagnostic Biomarkers for Diabetic Tubulointerstitial Injury.

Background: Tubulointerstitial injury plays a pivotal role in the progression of diabetic kidney disease (DKD), yet the link between neutrophil extracellular traps (NETs) and diabetic tubulointerstitial injury is still unclear. Methods: We analyzed microarray data (GSE30122) from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) associated with DKD's tubulointerstitial injury. Functional and pathway enrichment analyses were conducted to elucidate the involved biological processes (BP) and pathways. Weighted gene coexpression network analysis (WGCNA) identified modules associated with DKD. LASSO regression and random forest selected NET-related characteristic genes (NRGs) related to DKD tubulointerstitial injury. Results: Eight hundred ninety-eight DEGs were identified from the GSE30122 dataset. A significant module associated with diabetic tubulointerstitial injury overlapped with 15 NRGs. The hub genes, CASP1 and LYZ, were identified as potential biomarkers. Functional enrichment linked these genes with immune cell trafficking, metabolic alterations, and inflammatory responses. NRGs negatively correlated with glomerular filtration rate (GFR) in the Neph v5 database. Immunohistochemistry (IHC) validated increased NRGs in DKD tubulointerstitial injury. Conclusion: Our findings suggest that the CASP1 and LYZ genes may serve as potential diagnostic biomarkers for diabetic tubulointerstitial injury. Furthermore, NRGs involved in diabetic tubulointerstitial injury could emerge as prospective targets for the diagnosis and treatment of DKD.

Association of time-averaged serum uric acid level with clinicopathological information and long-term outcomes in patients with IgA nephropathy.

Objective: Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. Methods: This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Results: Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. Conclusions: The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.

Identification and validation of voltage-dependent anion channel 1-related genes and immune cell infiltration in diabetic nephropathy.

AIMS/INTRODUCTION: This study investigated the roles of voltage-dependent anion channel 1-related differentially expressed genes (VRDEGs) in diabetic nephropathy (DN). MATERIALS AND METHODS: We downloaded two datasets from patients with DN, namely, GSE30122 and GSE30529, from the Gene Expression Omnibus database. VRDEGs associated with DN were obtained from the intersection of voltage-dependent anion channel 1-related genes from the GeneCards database, and differentially expressed genes were screened according to group (DN/healthy) in the two datasets. The enriched pathways of the VRDEGs were analyzed. Hub genes were selected using a protein-protein interaction network, and their predictive value was verified through receiver operating characteristic curve analysis. The CIBERSORTx software examined hub genes and immune cell infiltration associations. The protein expression of hub genes was verified through immunohistochemistry in 16-week-old db/db mice for experimentation as a model of type 2 DN. Finally, potential drugs targeting hub genes that inhibit DN development were identified. RESULTS: A total of 57 VRDEGs were identified. The two datasets showed high expression of the PI3K, Notch, transforming growth factor-ß, interleukin-10 and interleukin-17 pathways in DN. Five hub genes (ITGAM, B2M, LYZ, C3 and CASP1) associated with DN were identified and verified. Immunohistochemistry showed that the five hub genes were highly expressed in db/db mice, compared with db/m mice. The infiltration of immune cells was significantly correlated with the five hub genes. CONCLUSIONS: Five hub genes were significantly correlated with immune cell infiltration and might be crucial to DN development. This study provides insight into the mechanisms involved in the pathogenesis of DN.

Chloroquine inhibits NLRP3 inflammasomes activation and alleviates renal fibrosis in mouse model of hyperuricemic nephropathy with aggravation by a high-fat-diet.

Numerous epidemiological studies have demonstrated that hyperuricemia (HUA) is a risk factor for renal diseases and renal fibrosis. Dietary patterns can influence serum urate levels and hyperuricemic nephropathy (HN). NLRP3 inflammasomes play a crucial role in various inflammatory responses and contribute to HN progression. Chloroquine (CQ) is an anti-inflammatory and disease-modifying anti-rheumatic drug (DMARD) utilized in treating autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this study, we examined the effects and underlying mechanisms of CQ in a high-fat-diet (HFD) exacerbated mouse model of HN. C57BL/6 mice were randomized into either a control group or an HN group (induced by adenine/potassium oxonate treatment), followed by a normal diet or HFD, with or without CQ treatment. Our findings revealed that the HN group exhibited elevated serum levels of blood urea nitrogen (BUN) and creatinine compared to the control group. Additionally, the HN + HFD group displayed increased serum levels of uric acid, BUN, and creatinine relative to the control + HFD group. Moreover, the HFD exacerbated renal uric acid crystal deposition and fibrosis in HN mice compared to a normal diet. CQ ameliorated renal dysfunction, as evidenced by reduced serum creatinine levels, renal fibrosis, and renal tubular injury scores, and significantly decreased NLRP3, ASC, caspase-1, and IL-1ß levels in HN mice. These findings suggest that CQ inhibits the activation of NLRP3 inflammasomes and may serve as a potential therapeutic strategy for HN treatment.

Acute kidney injury in patients with idiopathic membranous nephropathy: influencing factors and prognosis.

AIM: Idiopathic membranous nephropathy (IMN) is a common type of nephrotic syndrome, and is associated with acute kidney injury (AKI). We investigated the association of multiple variables with AKI in patients with IMN. METHODS: The data of 187 patients with biopsy-proven IMN were examined. Renal outcome was defined as progression to end-stage renal disease (ESRD). Binary logistic regression and Kaplan-Meier's analysis were used for statistical analysis. RESULTS: During follow-up, 46 (24.6%) patients developed AKI. The incidence of AKI was greater in males than females (p < .01). The AKI group had higher uric acid, lower serum PLA2R antibody positive, and worse baseline kidney function (all p < .01). Most patients in the AKI group had stage I (71.74%) or stage II (21.74%). The AKI group had higher renal tubular injury score and chronicity index (both p < .05). Binary logistic regression indicated that uric acid and baseline estimated glomerular filtration rate (eGFR) were independent risk factors for AKI in patients with IMN (p < .05). The optimal cutoff value of serum uric acid for predicting AKI was 402.50 µmol/L and the baseline eGFR was 96.83 mL/min/1.73 m2. Kaplan-Meier's analysis showed that the cumulative renal survival rate was lower in the AKI group (p = .047). CONCLUSIONS: AKI increases the risk of poor prognosis in IMN patients and the high uric acid and low baseline eGFR were considered independent predictors for developing AKI in patients with IMN.

Association of Red Blood Cell Life Span with Abnormal Changes in Cardiac Structure and Function in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.

Introduction: With the invention and improvement of the carbon monoxide (CO) breath test, the role of shortened red blood cell life span (RBCLS) in renal anemia, an independent risk factor for cardiovascular events in patients with chronic kidney disease (CKD), is gradually attracting attention. Considering that heart failure is the leading cause of morbidity and mortality in patients with CKD, this study investigated the correlation between the RBCLS and the cardiac structure and function in non-dialysis patients with CKD stages 3−5, aiming to provide new ideas to improve the long-term prognosis of CKD patients. Methods: One hundred thirty-three non-dialysis patients with CKD stages 3−5 were tested for RBCLS. We compared the serological data, cardiac ultrasound results, and follow-up prognosis of patients with different RBCLS. Results: As the RBCLS shortened, the patients' blood pressure, BNP, and CRP gradually increased, most significantly in patients with an RBCLS < 50 d. Patients with an RBCLS < 50 d had substantially lower hemoglobin (Hb), hematocrit, and albumin levels than those with an RBCLS ≥ 50 d. The cardiac ultrasound results show that patients with an RBCLS < 50 d had significantly larger atrial diameters than those with an RBCLS ≥ 50 d and were associated with more severe diastolic dysfunction. Patients with an RBCLS < 50 d had a 3.06 times greater risk of combined heart failure at baseline than those with an RBCLS ≥ 70 d and a higher risk of heart failure at follow-up. CKD stage 5 patients with an RBCLS < 50 d were more likely to develop heart failure and require renal replacement therapy earlier than patients with an RBCLS ≥ 50 d. Conclusions: In non-dialysis patients with CKD stages 3−5, there is a correlation between the red blood cell life span and cardiac structure and function. The RBCLS may also impact the renal prognosis of CKD patients.

Time-Averaged Hematuria as a Prognostic Indicator of Renal Outcome in Patients with IgA Nephropathy.

We aim to investigate the association of time-averaged hematuria (TA-hematuria) with the progression of IgA nephropathy (IgAN). Based on TA-hematuria during follow-up, 152 patients with IgAN were divided into a hematuria remission group (≤28 red blood cells [RBCs]/µL) and a persistent hematuria group (>28 RBCs/µL). The persistent hematuria group had a higher percentage of patients with macroscopic hematuria, lower levels of hemoglobin and TA-serum albumin, and more severe renal pathologic lesions. The composite endpoint is defined as a doubling of the baseline SCr level (D-SCr), or the presence of ESRD. During the mean follow-up of 58.08 ± 23.51 months, 15 patients (9.9%) reached the primary outcome of ESRD and 19 patients (12.5%) reached the combined renal endpoint. Kaplan-Meier analysis showed that the persistent hematuria group had a lower renal survival rate. The persistent hematuria patients who were incorporated with proteinuria (≥1.0 g/day) and low TA-serum albumin (<40 g/L) had the worst renal outcomes. Multivariate Cox regression indicated that TA-hematuria (hazard ratio [HR] = 0.004, 95% CI: 0.001, 0.008; p = 0.010) was independently associated with the progression of IgAN. Receiver operating characteristic analysis indicated the optimal TA-hematuria cutoff value for predicting the progression of IgAN was 201.21 RBCs/µL in females and 37.25 RBCs/µL in males.

An Identification Method for Rotor Direction Based on Charge Induction.

The detection of rotor motion is always key to ensure the normal operation of industrial sewing machines. This paper presents a novel method for rotor detection based on charge induction mechanism, which is suitable for industrial environments with high noise and electromagnetic radiation and is easy to install. Firstly, the principle of measuring rotor rotation based on charge induction is given. Then, the detection model of rotor direction identification based on two detection electrodes is established. Finally, details are given of the detection circuit design and the experiment that was carried out. The results show that the proposed method can effectively identify the noncontact rotor direction with and without occlusion, indicating that the method has excellent anti-interference capability. The accuracy of the method can be further improved by increasing the sampling rate and sampling points of the system.