Indices Of Renal Function Research Articles

Role of myo-inositol in acute kidney injury induced by cisplatin

There is an increasing evidence suggesting that myo-inositol (MI) may be a renoprotective factor. Our previous study revealed that decreased MI concentrations and increased excretion are often observed in animal models of renal injury and in patients with nephropathy. However, the role of MI supplementation in renal injury remains unclear. In this study, we aimed to explore the role of MI in cisplatin-induced acute kidney injury (AKI). We established a model of acute kidney injury caused by cisplatin (CDDP). Male Kunming mice were randomly divided into six groups: Sham (normal saline), CDDP (15 mg/kg), + MI (150 mg/kg), + MI (300 mg/kg), + MI (600 mg/kg) and MI (600 mg/kg). Human renal tubular epithelial cell line HK-2 cells were likewise separated into six groups at random: Control (normal saline), CDDP (20 µM), + MI (200 µM), + MI (400 µM), + MI (800 µM) and MI (800 µM). After the model was established, renal function indexes were subsequently detected, and experiments such as pathological staining analysis and protein expression analysis were performed. Our results showed that cisplatin administration led to AKI and apoptosis in mice and HK-2 cells, accompanied by markedly increased levels of MIOX, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), whereas exogenous MI significantly attenuated kidney injury and HK-2 cell damage induced by cisplatin both in vivo and in vitro by inhibiting excessive apoptosis. Overall, our findings demonstrate that exogenous MI can reduce excessive apoptosis, thus playing a protective role in cisplatin-induced AKI, indicating that exogenous MI may be used as an adjunctive treatment modality in cisplatin-induced AKI.

Study on the mechanism of Shenkang injection in the treatment of chronic renal failure based on the strategy of "Network pharmacology-Molecular docking-Key target validation".

To explore the potential mechanism of Shenkang injection (SKI) in the treatment of chronic renal failure based on network pharmacology and molecular docking technology, and to verify the core targets and key pathways by using the renal failure model. The active components and targets of Shenkang injection were retrieved by TCMSP database, and the disease related targets were obtained by OMIM, GeneCards and other databases. Then, the intersection was obtained, and were imported into String database for PPI analysis. After further screening of core targets, GO and KEGG analysis were performed. Autodock software was used to predict the molecular docking and binding ability of the selected active ingredients and core targets. Chronic renal failure (CRF) model was established by adenine induction in rats, and the pathological observation of renal tissues was conducted. Meanwhile, the effects of Shenkang injection and its active components on core targets and pathways of renal tissues were verified. The results of network pharmacology showed that the main components of Shenkang injection might be hydroxysafflor yellow A (HSYA)、tanshinol、rheum emodin、Astragaloside IV. Through enrichment analysis of core targets, it was found that Shenkang injection may play an anti-chronic renal failure effect through PI3K-Akt signaling pathway. Molecular docking results showed that the above pharmacodynamic components had strong binding ability with the target proteins PI3K and Akt. The results of animal experiments showed that renal function indexes of Shenkang injection group and pharmacodynamic component group were significantly improved compared with model group. HE staining results showed that the pathological status of the kidney was significantly improved in SKI and pharmacodynamic component treatment groups. Immunohistochemical results showed that the renal fibrosis status was significantly reduced in SKI and pharmacodynamic component treatment groups. q-RTPCR and WB results showed that the expression levels of PI3K and Akt were significantly decreased in the treatment groups (P< 0.05). Shenkang injection may inhibit PI3K-Akt signaling pathway to play an anti-chronic renal failure role through the pharmacodynamic component hydroxysafflor yellow A (HSYA), tanshinol, rheum emodin, Astragaloside IV.

CircRNA itchy E3 ubiquitin protein ligase improves mitochondrial dysfunction in sepsis-induced acute kidney injury by targeting microRNA-214-3p/ATP-binding cassette A1 axis

Background Circular RNAs (circRNAs) are promising biomarkers and therapeutic targets for acute kidney injury (AKI). In this study, we investigated the mechanism by which circRNA itchy E3 ubiquitin protein ligase (circ-ITCH) regulates sepsis-induced AKI. Methods A sepsis-induced AKI mouse model was created using LPS induction and circ-ITCH overexpression. Circ-ITCH levels were confirmed via RT-qPCR. Kidney tissue changes were examined through various stains and TUNEL. Enzyme-linked immunosorbent assay (ELISA) gauged oxidative stress and inflammation. Mitochondrial features were studied with electron microscopy. RT-qPCR and western blotting assessed mitochondrial function parameters. Using starBase, binding sites between circ-ITCH and miR-214-3p, as well as miR-214-3p and ABCA1, were predicted. Regulatory connections were proven by dual-luciferase assay, RT-qPCR, and western blotting. Results Circ-ITCH expression was downregulated in LPS-induced sepsis mice. Overexpression of circ-ITCH ameliorates indicators of renal function (serum creatinine [SCr], blood urea nitrogen [BUN], neutrophil gelatinase-associated lipocalin [NGAL], and kidney injury molecule-1 [Kim-1]), reduces renal cell apoptosis, mitigates oxidative stress markers (reactive oxygen species [ROS] and malondialdehyde [MDA]), and diminishes inflammatory markers (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF-α]). Moreover, circ-ITCH overexpression alleviated mitochondrial damage and dysfunction. Furthermore, circ-ITCH acts as a sponge for miR-214-3p, thereby upregulating ABCA1 expression. In addition, the miR-214-3p inhibitor repressed oxidative stress, inflammation, and mitochondrial dysfunction, which was reversed by circ-ITCH knockdown. Further cellular analysis in HK-2 cells supported these findings, highlighting the protective role of circ-ITCH against sepsis-induced AKI, particularly through the miR-214-3p/ABCA1 axis. Conclusion The novel circ-ITCH/miR-214-3p/ABCA1 pathway plays an essential role in the regulation of oxidative stress and mitochondrial dysfunction in sepsis-induced AKI.

Impact of Using Natural Herbal Materials for Acupoint Application Combined with an Evidence-Based Supervision Method on Improving Renal Function and Lifestyle Treatment in Hemodialysis Patients

Natural herbal materials are commonly derived from plants, minerals, and animals, and compared to synthetic drugs, are closer to natural resources. Here, we analyzed the impact of using evidence-based supervision in combination with natural herbal materials for acupoint application on renal function and lifestyle treatment in hemodialysis patients, with the aim to provide evidence for clinical practice. We selected 80 patients who underwent hemodialysis treatment in our hospital between September 2021 and December 2022 as the research subjects. All of the research subjects were randomly divided into observation and control groups, with 40 cases in each group. The control group received conventional nursing interventions, while the observation group received interventions using acupuncture point application of natural Traditional Chinese medicine herbal materials combined with evidence-based supervision. The main endpoints were to compare the nursing intervention effects between the two groups, including patients’ renal function indicators and quality of life. The natural Chinese medicinal herb Atractylodes macrocephala contains eucalyptol-type sesquiterpene lactones, which exhibit various activities, especially in anti-inflammatory aspects, with a definite effect on the prevention and treatment of renal fibrosis in hemodialysis patients. Clinical studies have shown that the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) in the observation group were lower than those in the control group, while the GQOLI-74 scores of the observation group were higher than those of the control group (all P &gt;0.05). Natural Chinese medicines are natural biobased materials that are often described as compound drugs in practical clinical applications, containing multiple components that can work synergistically to produce comprehensive therapeutic effects. Among them, Atractylodes macrocephala has a definite effect on the prevention and treatment of renal fibrosis in hemodialysis patients. The use of natural Chinese medicinal materials in acupoint application combined with evidence-based supervisory methods has shown precise clinical effects in hemodialysis patients, not only by improving renal function but also significantly enhancing their quality of life.

Differential effects on renal function and glucose metabolism of renal dependent bezafibrate and non-renal dependent pemafibrate in patients with hypertriglyceridemia.

Among fibrates as triglyceride-lowering agents, bezafibrate and fenofibrate are predominantly renally excreted, while pemafibrate is mainly hepatically metabolized and biliary excreted. To elucidate possible different properties among fibrates, this retrospective observational study examined the changes in clinical laboratory parameters, including indices of renal function and glucose metabolism, in cases of switching from bezafibrate to pemafibrate. In 93 patients with hypertriglyceridemia, the average values of laboratory parameters including serum creatinine, estimated glomerular filtration rate (eGFR), plasma glucose, and hemoglobin A1c on respective two occasions before and after switching from bezafibrate to pemafibrate were evaluated. Triglycerides, low-density and high-density lipoprotein cholesterol, creatine kinase, and uric acid did not change before and after switching from bezafibrate to pemafibrate. Serum creatinine significantly decreased and eGFR significantly increased after switching from bezafibrate to pemafibrate (p<0.001, respectively). Plasma glucose tended to increase (p=0.070) and hemoglobin A1c significantly increased (p<0.001) after switching to pemafibrate. The degrees of changes in creatinine, eGFR, glucose, and hemoglobin A1c before and after drug switching were not affected by the presence or absence of coexisting disease, and with or without drug treatment including statin and renin-angiotensin system inhibitor. Our findings indicate that switching from bezafibrate to pemafibrate produces a significant decrease in serum creatinine and increases in eGFR and hemoglobin A1c in patients with hypertriglyceridemia, suggesting that the effects on renal function and glucose metabolism differ among fibrates.

Association of Normal and Mutated APOL1 G2 Rs60910145 alleles with SCD, Body Mass Index, and Renal Function Biomarkers and Indices

Purpose of the study: The current study aimed to detect the frequency of normal and mutated APOL1 alleles in sickle cell disease (SCD) patients and test their relation with Microalbuminuria, Creatinine, Urea, Glomerular Filtration Rate (GFR), and Body Mass Index (BMI). Patients and Methods: The study included 156 SCD subjects. Serum Creatinine (mg/dl) and Urea (mg/dl) as well as Microalbuminuria (mg/l) level were measured by using Biosystems kit (Biosystems, Barcelona, Spain) and Mindary BA88A semi-automated biochemistry analyzer. Glomerular filtration rate and body mass index were calculated by equations. Blood DNA extraction was achieved by using the modified G-DEX™IIb Genomic DNA Extraction Kit protocol. The PCR was done for the detection of the APOL1 G2 rs60910145 alleles by using allele-specific PCR and primers. Results: The CC allele was more frequent in study cases (66.7%) than TT allele. The frequency of a mutated allele (CC) was insignificantly higher in males (67.8%) than in females (65.2%) and in rural (70.9%) than urban areas. It is also higher in Shankhab compared to other tribes and subjects 26-37 years compared to other, P˃0.05. Interstingly, the subjects who carry the CC allele showed a significantly higher level of Microalbuminuria, Creatinine, BMI, and Urea compared to those carry TT allele. Moreover, GFR is also higher in subjects who carry CC than TT allele but it is not significant. Conculsion: Altogether, the study findings highlighted the link of normal and mutated APOL1 G2 rs60910145 alleles with SCD and displayed the significant value of mutated APOL1 allele in the prediction of early nephropathy in SCD patients.

Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.

Clinical Significance of Serum Creatinine, Urea Nitrogen and Uric Acid Levels in Patients with Chronic Renal Failure

Chronic renal failure (CRF) is a clinical syndrome characterized by chronic progressive renal parenchymal damage caused by various reasons, resulting in obvious atrophy of the kidney and inability to maintain basic functions. Metabolite retention, imbalance of water, electrolyte and acid-base balance, and systemic involvement of various systems are the main manifestations in clinic. Due to its complicated metabolic disorder, once it develops to the stage of renal failure or even the end stage of uremia, it is often more difficult to treat other renal diseases. Therefore, early detection, early diagnosis and early treatment of chronic renal failure are of great significance to improve the therapeutic effect of patients. In this project, 150 subjects were divided into chronic renal failure group (75 cases) and healthy group (75 cases). By analyzing the data of renal function indexes (blood creatinine, urea nitrogen, uric acid) of patients with chronic renal failure and healthy control group, the clinical significance of blood creatinine, urea nitrogen and uric acid level detection for chronic renal failure was discussed, and the importance of blood creatinine, urea nitrogen and uric acid monitoring for chronic renal failure was explained, providing scientific basis for timely prevention or delay of chronic renal failure. Biochemical tests were carried out on 150 serum samples from the combined healthy group of chronic renal failure. the values of uric acid, urea nitrogen and serum creatinine detected by the two groups were counted and treated with statistical methods. the results showed that the values of urea nitrogen, uric acid and serum creatinine in the chronic renal failure group were significantly higher than those in the healthy group, and the same indexes in the two groups were compared, P&lt;0.05. statistics showed that the difference of the same data between the two groups was significant. Serum uric acid, urea nitrogen and creatinine are easy to detect and the test results are relatively accurate. The results can be used for auxiliary diagnosis of patients with chronic renal failure and have clinical significance for diagnosis of patients with chronic renal failure.

Association between paraben exposure and renal function index among the general Taiwanese

Association between paraben exposure and renal function index among the general Taiwanese

Potential Effects of Digoxin on Renal Functions in Patients With Congestive Heart Failure.

Renal dysfunction is a common complication among patients with congestive heart failure (CHF) and can significantly impact their management, especially when medications like digoxin are involved. The clearance of digoxin is closely tied to the glomerular filtration rate (GFR), which suggests that the safety and efficacy of digoxin may vary with renal function. Therefore, this study aimed to assess the potential effects of digoxin on renal function in patients diagnosed with CHF at a tertiary hospital in the Asir region of Saudi Arabia. A retrospective study examined the records of 30 CHF patients treated with digoxin. Renal function markers like estimated GFR (eGFR), creatinine, blood urea nitrogen (BUN), albumin, and urine levels were compared before and after digoxin treatment. Liver enzymes and other relevant parameters were also examined. A statistical analysis using t-tests was conducted to evaluate the changes in renal function indicators before and after digoxin treatment. The mean eGFR decreased significantly from 65.4 ± 8.9 mL/min/1.73m2 before digoxin to 57.7 ± 7.8 mL/min/1.73m2 after (p = 0.001). Creatinine, BUN, albumin, and urine levels showed no significant changes. Digoxin significantly increased aspartate aminotransferase (AST) from 34.5 ± 11.6 U/L to 53.8 ± 14.6 U/L (p = 0.002), alanine aminotransferase (ALT) from 38.5 ± 12.6 U/L to 55.3 ± 17.6 U/L (p = 0.013), and creatine kinase from 117.7 ± 22.5 U/L to 133.9 ± 15.8 U/L (p = 0.012). Hemoglobin decreased significantly from 12.8 ± 1.4 g/dL to 12.1 ± 1.4 g/dL (p = 0.034). No significant changes occurred in myoglobin, troponin, bilirubin, platelets, potassium, calcium, or chloride levels. Effects on kidney function did not differ significantly by gender or age, except blood urea nitrogen was higher in patients over 50 years (8.3 ± 2.3 vs. 5.6 ± 2.7 mg/dL, p = 0.015). This study suggests digoxin may adversely affect renal function in CHF patients, as evidenced by reduced eGFR. However, the small retrospective design limits definitive conclusions. Further prospective research with larger samples is warranted to elucidate digoxin's renal effects in CHF patients.

Effect of sitagliptin combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in early diabetic nephropathy.

Early diabetic nephropathy (DN) is a complication of diabetes mellitus. It mainly affects kidney microvessels and glomerular function, and its timely and effective treatment is critical for early DN. However, the effects of treatments comprising simple Western medicine are not optimal. With the promotion and implementation of integrated Chinese and western medicine treatments, remarkable results have been achieved for many diseases. To this end, we explored the clinical efficacy of integrated traditional Chinese and western medicines for the treatment of early DN. To investigate the effect of sitagliptin tablets combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in patients with early DN. Through a retrospective analysis, 123 patients with early DN were admitted to the endocrinology clinic of the Changzhou NO. 7 People's Hospital from January 2021 to October 2022 and were selected as study subjects. After rigorous screening, 100 patients with early DN were enrolled. The control group (CG, n = 50) and the observation group (OG, n = 50) were divided according to the treatment method. The CG were treated with sitagliptin, and the OG were treated with sitagliptin plus the Yiqi yangyin huoxue decoction. Both groups were treated for 3 mo. For both groups, the baseline data and clinical efficacy were compared, and changes in blood glucose levels, lipid levels, renal function, and hematological indicators before (T0) and after (T1) treatment were assessed. The total effective rate for the OG was 94.00% and that of the CG was 80.00% (P < 0.05). After treatment (T1), the levels of fasting blood glucose, 2 h postprandial glucose, total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in OG patients were obviously lower than those in the CG (P < 0.05), and cystatin C, homocysteine, urinary microalbumin, and blood creatinine values in OG patients were also obviously lower than those in the CG (P < 0.05); erythrocyte deposition, plasma viscosity, whole blood high shear viscosity, and whole blood low shear viscosity were markedly lower in OG patients than in the CG (P < 0.05). Sitagliptin combined with Yiqi yangyin huoxue decoction has a remarkable effect when used to treat patients with early DN. Further, it is helpful in improving hemorheological indices and controlling disease progression.

The therapeutic effects of fermented milk with lactic acid bacteria from traditional Daqu on hypertensive mice

Lactic acid bacteria (LAB), a type of microorganism widely used in functional foods, has gained notable research attention in recent years. Certain strains possess the proteolytic ability to release potentially antihypertensive peptides from dairy proteins, which prompted us to explore the LAB strains from an understudied and unique ingredient, Daqu. We screened for 67 strains of LAB strains from traditional Daqu using the calcium dissolution ring method. Sixteen strains exhibiting angiotensin-converting enzyme inhibition (ACE-I) activity exceeding 50% were chosen for 16S rDNA sequencing and safety assessment. It is noteworthy that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 exhibited significant ACE-I activity, which was the result of strain fermentation in reconstituted skim milk. These 2 strains did not exhibit hemolytic activity or antibiotic resistance. They also did not produce biogenic amines and showed high survival rates in the gastrointestinal tract. Additionally, Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 fermented milk exhibited a notable reduction in blood pressure levels in spontaneously hypertensive rats (SHR) compared with negative controls in SHR. Importantly, no adverse effect was observed in normal Wistar-Kyoto rats. Through the analysis of physiological, serum, and urine-related indicators, it was observed that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 have the potential to promote weight gain in SHR, alleviate excessive heart rate, improve renal function indicators, and effectively regulate blood sugar and uric acid levels in SHR. These 2 strains showed optimal properties in lowering blood pressure and have the potential to be used in functional dairy products in the future.

LncRNA 152 attenuates lipopolysaccharide-induced acute kidney injury in rats by regulating the FGF23/Klotho/MAPK axis.

This study aimed to explore the effect and related mechanisms of LncRNA 152 in acute kidney injury (AKI). QRT-PCR was used to detect the expression of LncRNA 152, FGF23 and Klotho in the serum of patients with AKI. Subsequently, Sprague Dawley (SD) rats were induced into AKI animal model by lipopolysaccharide (LPS). Then, H&E staining was performed to observe the pathological changes in the rat kidney tissues; qRT-PCR to detect the expression of LncRNA 152, FGF23 and Klotho in the rat kidney tissues; biochemical assay and ELISA to assess the levels of renal function indexes and inflammatory factors in rat serum, as well as oxidative stress indexes in kidney tissues; and western blot to measure the protein expressions of FGF23, Klotho, p-p38 and p38 in rat kidney tissues. LncRNA 152 was significantly down-regulated in serum of AKI patients and kidney tissues of AKI rats. In AKI patients, LncRNA 152 was negatively correlated with FGF23 expression while positively correlated with Klotho expression. LncRNA 152 overexpression reduced the levels of blood urea nitrogen (BUN), creatinine (Cr) and cystatin C (Cys-C) and inflammatory factors in serum of AKI rats and attenuated pathological damage and oxidative stress of kidney tissues. In addition, LncRNA 152 overexpression also decreased FGF23 expression and p-p38/p38 ratio while up-regulated Klotho expression in the kidney tissues of AKI rats. LncRNA 152 attenuates oxidative stress and inflammatory responses by regulating the FGF23/Klotho axis and inhibiting the MAPK signalling pathway in rat kidney tissues, thereby ameliorating LPS-induced AKI.

Comparison of the effect of hemodialysis and peritoneal dialysis in the treatment of end-stage renal disease.

To compare the clinical effects of hemodialysis (HD) and peritoneal dialysis (PD) in the treatment of end-stage renal disease (ESRD) patients. Clinical data of ESRD patients who received HD (n=74) and PD (n=77) for more than 12 months in the First People's Hospital of Tonglu County from October 2020 to November 2021 were retrospectively selected. Renal function indexes, blood pressure, and complication rates in the two groups before the first dialysis and at the end of the observation period were compared. After the dialysis, the urea nitrogen (BUN) levels decreased in both groups, and were significantly lower in the PD group compared to the HD group. Urea clearance index (Kt/V) increased, and were significantly higher in the PD group compared to the HD group (P<0.05). After the dialysis, albumin (ALB) and cardiac ejection fraction (EF) levels significantly increased, and ALB levels were significantly higher in the HD group while EF levels were significantly higher in the PD group (P<0.05). Levels of whole parathyroid hormone (iPTH), systolic blood pressure, and diastolic blood pressure indicators in both groups decreased compared to before the dialysis, and were significantly lower in the PD group compared to the HD group of patients (P<0.05). PD was associated with significantly lower total incidence of complications compared to HD (P<0.05). Peritoneal dialysis is more effective in maintaining the hemodynamic stability for ESRD patients, reducing blood pressure level, improving the clearance rate of molecular substances, and protecting the renal function of patients compared to hemodialysis.

Effects of liraglutide on extraglycemic inflammatory markers and renal hemodynamic parameters in diabetic kidney disease (DKD).

Diabetic kidney disease (DKD) was the leading cause of kidney disease, which has been a crucial public health. Liraglutide is a drug, widely used for DKD treatment globally. However, the extraglycemic inflammatory markers and renal hemodynamic parameters of DKD patients treated with liraglutide has been not reported. In this study, 160 patients with early DKD were enrolled, 80 cases in the control group and 80 cases in the treatment group, respectively. The individuals in the control group were treated with metformin, while the individuals in the treatment group were treated with liraglutide and metformin for 3 months. The urinary microalbumin and urinary creatinine was measured to calculate the ratio (UACR), while the Doppler ultrasound were measured before and after treatment. After 3 months of treatment, body mass index (BMI), waist circumference (WC) and low-density lipoprotein cholesterol (LDL) in the treatment group were significantly decreased compared with before and after treatment in the control group; the levels of cystatin and UACR in treatment group were lower than before treatment and control group; The end-diastolic blood flow velocity (EDV) of renal artery and segment artery in treatment group was significantly higher than that before treatment and control group; The levels of CRP, TNF-α and IL-6 in the treatment group after treatment were lower than those before treatment and those in the control group. After 3 months of treatment, blood cystatin in the treatment group decreased significantly compared with before treatment and after treatment in the control group, with statistical significance After 3 months of treatment, the EDV of renal artery and renal segment in treatment group was significantly higher than that before treatment and control group, the peak systolic blood flow velocity (PSV) and EDV of renal interlobar artery in treatment group were significantly higher than those before treatment and control group. The resistance index (RI) was significantly lower than that before treatment and control group. Liraglutide can reduce inflammatory indicators, renal artery blood flow and renal function indicators in early DKD patients.

Celastrol attenuates diabetic nephropathy by upregulating SIRT1-mediated inhibition of EZH2related wnt/β-catenin signaling.

Proteinuria is an independent risk factor for the progression of diabetic nephropathy (DN) and an imbalance in podocyte function aggravates proteinuria. Celastrol is the primary active ingredient of T. wilfordii, effective in treating DN renal injury; however, the mechanisms underlying its effect are unclear. We explored how celastrol prevents DN podocyte damage using in vivo and in vitro experiments. We randomly divided 24 male C57BLKS/J mice into three groups: db/m (n=8), db/db (n=8), and celastrol groups (db/db+celastrol, 1mg/kg/d, gavage administration, n=8). In vivo experiments lasted 12weeks and intervention lasted ten weeks. Serum samples and kidney tissues were collected for biochemical tests, pathological staining, transmission electron microscopy, fluorescencequantitation polymerase chain reaction, and western blotting analysis. In vitro experiments to elaborate the mechanism of celastrol protection were performed on high glucose (HG)-induced podocyte injury. Celastrol reduced blood glucose levels and renal function index in db/db mice, attenuated renal histomorphological injury and glomerular podocyte foot injuries, and induced significant anti-inflammatory effects. Celastrol upregulated silent information regulator 2 related enzyme 1(SIRT1) expression and downregulated enhancer of zeste homolog (EZH2), inhibiting the wnt/β-catenin pathway-related molecules, such as wnt1, wnt7a, and β-catenin. SIRT1 repressed the promoter activity of EZH2, and was co-immunoprecipitated with EZH2 in mouse podocyte cells (MPC5). SIRT1 knockdown aggravated the protective effects of celastrol on MPC5 cells. Celastrol protected podocyte injury via SIRT1/EZH2, which participates in the wnt/β-catenin pathway. Overall, celastrol-mediated SIRT1 upregulation inhibited the EZH2-related wnt/β-catenin signaling pathway to attenuate DN and podocyte injury, providing a theoretical basis for celastrol clinical application.

The value of plasma presepsin as a diagnostic and prognostic biomarker for sepsis in Southern China.

Presepsin is a soluble CD14 subtype that has been considered as a novel marker for patients with sepsis.This study explored the clinical value of presepsin for sepsis in Southern China, and further established models for diagnosis and prognosis of sepsis through using machine learning (ML), by combining presepsin and other laboratory parameters. 269 subjects (105 infected patients, 164 sepsis and septic shock) and 198 healthy controls were enrolled. Laboratory parameters (hematological parameters, coagulation parameters, liver function indices, renal function indices, and inflammatory markers) were collected. Plasma presepsin was tested by chemiluminescence enzyme immunoassay. ML of DxAI™ Research platform was used to establish diagnostic and prognostic models. Sensitivity, specificity, and other performance indicators were used to evaluate the performance of each model. The level of presepsin was obviously increased in sepsis and sepsis shock, compared with that of infected and healthy group (all P < 0.0001). Presepsin concentration was positively correlated with positive blood culture and 30-day mortality in sepsis and septic shock patients. Through ROC curve analysis, Hb, UREA, APTT, CRP, PCT, and presepsin were incorporated into machine learning to construct diagnosis models. Ada Boost model had the best diagnostic efficiency (AUC: 0.94 (95% CI 0.919-0.968) in the training set and AUC: 0.86 (95% CI 0.813-0.900) in validation set). Furthermore, AST, APTT, UREA, PCT, and presepsin were included in the prognosis ML models, and the Bernoulli NB model had greater predictive ability for 30-day mortality risk of sepsis (AUC: 0.706), which was higher than that of PCT (AUC: 0.617) and presepsin (AUC: 0.634) alone. Machine-learning model based on presepsin and routinely laboratory parameters showed good performance of diagnostic and prognostic ability for sepsis patients.

Neutrophil elastase in dexmedetomidine alleviating sepsis-related renal injury in rats.

This research was to investigate the mechanism of neutrophil elastase (NE) in dexmedetomidine (DEX) alleviates sepsis-related renal injury in rats. Sixty healthy male SD rats aged 6-7weeks were randomly assigned to the control group (Sham group (S group)), Model group (M group), Model+DEX group (M+DEX group), and Model+DEX+Elaspol group (M+DEX+Elaspol (sivelestat) group), with 15 rats in each group. The renal morphology and pathological changes of different groups of rats after modeling were observed, and renal tubular injury was scored. Serum samples were collected at 6h, 12h, and 24h after modeling, and the rats were sacrificed. Renal function indicators, including neutrophil gelatinase-associated lipoprotein (NGAL), kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), NE, serum creatinine (SCr), and blood urea nitrogen (BUN), were analyzed by enzyme-linked immunosorbent assay at different time periods. The level of NF-кB in renal tissue was detected by immunohistochemistry. It was revealed that the general color of renal tissue in M group was dark red, swollen, and congested, and the renal tubular epithelial cells were significantly enlarged, with obvious vacuolar degeneration and inflammatory cell infiltration. Compared with M group, the color and morphology of renal tissue in M+DEX group and M+DEX+Elaspol group were improved, and the amount of inflammatory cell infiltration was reduced. The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M group were significant different from S group 12h after the operation (P<0.001). The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M+DEX group were significant different from M group (P<0.01). The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M+DEX+Elaspol group were significant different from those in M group at 12h after the operation (P<0.001). NE plays an active role in the reduction of sepsis-related renal injury in rats by inhibiting the inflammatory response.

Polygonum cuspidatum Sieb. et Zucc. Extracts improve sepsis-associated acute kidney injury by inhibiting NF-κB-mediated inflammation and pyroptosis

Ethnopharmacological relevancePolygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) is a herbaceous perennial plant in the Polygonaceae family that produces biofunctional stilbenes and quinones. The dried rhizome and root of P. cuspidatum in traditional oriental medicine have been used for ameliorating inflammatory illnesses, diabetes, gout, cancer, and other ailments. Aim of the studyThis work aimed to investigate the protective effects of P. cuspidatum extracts (PCE) on sepsis-associated acute kidney injury (SA-AKI) and its underlying mechanism. Materials and methodsThe potential mechanisms by which PCE improved SA-AKI were preliminarily predicted by network pharmacology. The dry powders of PCE were obtained using the freeze-drying method. A mouse model of SA-AKI was established by intraperitoneal injection of lipopolysaccharide (LPS). The protective effects of PCE on SA-AKI in vivo were studied using pathological and biochemical methods. LPS-stimulated HK-2 cells were prepared for in vitro evaluation. The qPCR and immunoblotting assays were performed to confirm the mechanism involved. ResultsThe network pharmacology results indicate that emodin (Emo) and polydatin (PD) are potential active components of P. cuspidatum ameliorating SA-AKI. The experimental results showed that PCE improved renal function indices (creatinine, urea nitrogen, and urinary protein) in SA-AKI mice. Mechanistically, PCE mitigated oxidative stress, regulated the expression levels of pyroptosis-related proteins, and repressed the production of inflammatory cytokines by inactivating nuclear factor-kappa B (NF-κB) signaling in vivo. Similar results were observed in LPS-stimulated HK-2 cells in the presence of Emo or PD. ConclusionsOur results demonstrated that PCE and active ingredients (Emo and PD) in PCE ameliorated SA-AKI by suppressing oxidative stress, inflammation, and pyroptosis.

The impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney: A retrospective cohort study

IntroductionThe preoperative examination of kidney transplantation includes HLA antibody screening to initially determine the presence of preexisting donor-specific antibody (DSA) that mediates hyperacute rejection. Recipients with positive HLA antibodies require further HLA specificity analysis to type the antigen and determine the antigen mismatches between the donor and recipient. However, recipients with suspected antibodies would have no further HLA specificity analysis. It is unclear whether suspected HLA antibodies would affect renal graft function. This study aimed to explore the impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney and thus determine the necessity of routinely performing the HLA specificity analysis in recipients with suspected HLA antibodies preoperatively. MethodsThis is a single-center retrospective cohort study. 179 kidney transplant recipients (KTRs) were included and further divided into HLA antibody-negative group (Group 1) and HLA antibody-suspected groups (Group 2) based on the result of the pretransplant HLA antibody screen test. And the antibody-suspected group was further divided into a low-mismatched group (Group A) and a high-mismatched group (Group B) according to the HLA specificity analysis. We tracked the renal function indexes, biochemical indexes, and posttransplant adverse events within 5 years after transplantation and explored the necessity of further HLA specificity analysis in recipients with pretransplant suspected HLA antibodies. ResultsThere was no statistically significant difference in demographics between HLA antibody-negative group and HLA antibody-suspected groups. At 5 years of follow-up, the KTRs in HLA antibody-negative group had significantly higher eGFR levels, lower serum creatinine levels, and less urinary protein compared to those in antibody-suspected group. Meanwhile, the KTRs in low-mismatched group also had significantly higher eGFR levels, lower serum creatinine levels, and less proteinuria compared to those in high-mismatched group. Correlation analysis showed that the age of KTRs, urinary protein levels and the load capacity of HLA mismatches were associated with eGFR levels of KTRs at 5 year posttransplant. ConclusionKTRs with suspected HLA antibodies before kidney transplantation have worse graft function than the preoperative HLA antibody-negative recipients in the long-term posttransplant follow-up. The specific load capacity of HLA mismatches, the age of the recipient and the urinary protein was found to be negatively correlated with long-term posttransplant renal outcomes. It is necessary to undergo further HLA specificity analysis for recipients with suspected HLA antibodies in HLA antibody screen test to explicit HLA mismatches and improve long-term posttransplant outcomes.