Kidney Disease Research Articles

Fitwalking: A New Frontier for Kidney Patients. A Center' s Experience.

Physical inactivity is common in patients with chronic kidney disease (CKD) and is an important modifiable risk factor for mortality, morbidity, and reduced quality of life. The present single-centre pilot study evaluated the possibility of performing structured physical exercise using a specific walking model, Fitwalking, in a population of patients with CKD and, according to the American College of Rheumatology guidelines, also in a population with immuno-rheumatological disease. Patients were recruited from the nephrology, haemodialysis, peritoneal dialysis, transplantation, and immuno-rheumatology outpatient clinics. After general and functional clinical evaluation and exercise prescription at the Department of Sports Medicine, we performed scientifically proven tests on CKD (Six-minute walk test and Sit to stand test), before and after the Fitwalking technique training course, and again after 6 and 12 months, to evaluate its effectiveness and identify any critical issues. We enrolled 80 patients, (41 males, 51.2%), mean age 53±12 years; the clinical data showed statistically significant improvements in systolic, average, and differential blood pressure, average speed, and physical strength. Participants also adapted to muscle fatigue, experienced a reduction in BMI with stable lean mass and reduced fat mass, and reported improved perceptions of physical and mental health, and quality of life. All enrolled patients successfully completed the process. A specific prescription was used that provided health education and allowed for the implementation of structured physical activity that could be performed safely and independently even after the training period. The activity was sustainable thanks to the training of in-house medical and nursing staff, demonstrating that it is possible to overcome this type of barrier to physical activity in CKD and in immuno-rheumatological patients.

Renal diseases in children at the university of Gondar hospital, Ethiopia: pattern and outcome

Background: In developing countries, renal diseases in children are becoming common causes of morbidity and mortality. In Ethiopia, there are no adequate data about patterns and outcome of these disorders. We conducted this study to provide evidences on patterns and outcome of renal diseases in children admitted to a tertiary hospital in Gondar, Ethiopia. Methods: A retrospective record review of all pediatric patients admitted with renal diseases over a period of two-years (January 2022-December 2023) to the university of Gondar hospital (UoGH), was conducted. Results: A total of 456, comprising 231 (50.7%) females and 225 (49.3%) males, patients were studied. Majority (37.7%) of patients were below 5 years of age. Renal diseases accounted for 3.6% of all admissions during the 2-years period. Common renal problems were urinary tract infection (UTI) (29%), acute glomerulonephritis (AGN) (24.1%), nephrotic syndrome (18.6%), acute kidney injury (AKI) (14.3%), nephroblastoma (9%) and chronic kidney diseases (CKD) (2.4%). Finally; 71.9% were discharged improved and 10.5% died. The highest case fatality rates were in patients with rapidly progressive glomerulonephritis (36.7%) followed by CKD (36.4%), and AKI (21.5%). Conclusions: This study revealed high prevalence and mortality rate of renal diseases in children. The major causes of death were AGN/RPGN, CKD and AKI. All the above evidences clearly disclosed that establishment of a pediatric nephrology unit and get a trained pediatric nephrologist in our university hospital is critical.

Formulae for estimation of kidney function as an approach to calculating drug doses: A scoping review

Background: The kidneys are the main organ for drug excretion, and it is critical to assess kidney function when designing dosage regimens for drugs that undergo renal elimination. Various formulae have been used to estimate kidney function and safely adjust doses. Objective: This research reviewed studies that assessed patients' kidney function with various approaches to provide appropriate choices of kidney function estimation formulas based on patients' age and clinical conditions. Method: The search involved browsing scientific articles in PubMed and ScienceDirect with the keywords (("assessment") AND ("GFR") AND ("formula")) OR ("renal function") AND ("human")) AND (“Creatinine”). The articles included were those available in full text and English. Thirty articles addressing the formulae for kidney function assessment were reviewed. Result: The Schwartz formula is more appropriate for pediatric and adult patients, whereas the creatinine-based chronic kidney disease epidemiology (CKD-EPI) formula can be used in geriatrics, obese patients, and patients already known to have decreased kidney function. The cystatin C-based CKD-EPI formula is for patients with HIV and post-transplant patients. Conclusion: This study identified that physiological conditions, especially patients’ age and pathology, should be considered in devising formulae to estimate kidney function to accurately calculate safe drug doses.

EFEKTIVITAS PENDIDIKAN KESEHATAN MENGGUNAKAN VIDEO TERHADAP KEPATUHAN PEMBATASAN CAIRAN PADA PASIEN HEMODIALISA DI KLINIK PANDAONI MEDIKA JAKARTA

Chronic kidney disease is a metabolic disease that can be seen in a decrease in kidney function. Patients with chronic kidney failure who do hemodialysis have a lot of fluid overload problems that cause an increase in IDWG. Patients who have excess fluids need to limit fluids. One effort to increase adherence is to provide education in advance to increase knowledge about the disease by providing health education using video. The purpose of this study was to determine the effectiveness of health education using video on compliance with fluid restrictions in hemodialysis patients at the Klinik Pandaoni Medika Jakarta. This study used a quantitative approach with a quasi-experimental design with two control groups for pre- and post-tests. The sampling technique used was purposive sampling on a total sample of 78 respondents. The analysis used is a paired sample t-test and an independent t-test. After the intervention was carried out and the results obtained, the intervention group experienced an average decrease indicating the influence of health education using video (p = 0.000), while in the control group the average compliance value increased with a value of p = 0.002, which indicated the influence of health education using video with a bad influence on the level of adherence to fluid restriction in the control group. There were differences in adherence to fluid restriction in the intervention group and the control group (p = 0.000).

An LC-MS/MS method for the simultaneous determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma and its clinical application in patients with chronic kidney disease.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry method for the determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma samples. Strata-X 33 μm solid-phase extraction cartridges were used for the extraction of the catecholamines from human plasma samples. The catecholamines were separated in a 150 × 3 mm Shim-pack GIST C18-AQ column with 3μm particle size, placed in an oven at 40°C and perfused with 82% mobile phase A (acetonitrile-H2O; 90:10, v/v) + 0.4% acetic acid and 18% mobile phase B (deionized H2O) + 0.2% formic acid at a flow rate of 340 μl/min in isocratic mode. The injected volume was 4 μl and the run lasted 4 min. The method was linear from 0.1 to 20 ng/ml and the lower limit of quantification was 0.1 ng/ml for all analytes. The method was applied to evaluate the plasma levels of catecholamines in plasma of patients with chronic kidney disease and allowed the detection for the first time of circulating levels of the novel catecholamines 6-bromodopamine and 6-cyanodopamine.

Revitalizing the Gut Microbiome in Chronic Kidney Disease: A Comprehensive Exploration of the Therapeutic Potential of Physical Activity

Revitalizing the Gut Microbiome in Chronic Kidney Disease: A Comprehensive Exploration of the Therapeutic Potential of Physical Activity

Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial.

The SELECT trial previously reported a 20% reduction in major adverse cardiovascular events with semaglutide (n = 8,803) versus placebo (n = 8,801) in patients with overweight/obesity and established cardiovascular disease, without diabetes. In the present study, we examined the effect of once-weekly semaglutide 2.4 mg on kidney outcomes in the SELECT trial. The incidence of the pre-specified main composite kidney endpoint (death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent estimated glomerular filtration rate (eGFR) < 15 ml min-1 1.73 m-2, persistent ≥50% reduction in eGFR or onset of persistent macroalbuminuria) was lower with semaglutide (1.8%) versus placebo (2.2%): hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.63, 0.96; P = 0.02. The treatment benefit at 104 weeks for eGFR was 0.75 ml min-1 1.73 m-2 (95% CI 0.43, 1.06; P < 0.001) overall and 2.19 ml min-1 1.73 m-2 (95% CI 1.00, 3.38; P < 0.001) in patients with baseline eGFR <60 ml min-1 1.73 m-2. These results suggest a benefit of semaglutide on kidney outcomes in individuals with overweight/obesity, without diabetes.ClinicalTrials.gov identifier: NCT03574597 .

Metabolomic and Physiological Effects of a Cardiorenal Protective Diet Intervention in African American Adults with Chronic Kidney Disease

Metabolomic and Physiological Effects of a Cardiorenal Protective Diet Intervention in African American Adults with Chronic Kidney Disease

Impact of lactate/albumin ratio on prognostic outcomes in patients with concomitant heart failure and chronic kidney disease.

Previous studies have linked the lactate/albumin (L/A) ratio to poor outcomes in various conditions, but its connection to mortality in patients with both heart failure (HF) and chronic kidney disease (CKD) remains unclear. Using data from 1537 patients in MIMIC-IV, this study examined the relationship between L/A ratio and in-hospital and one-year mortality, employing Cox models, Kaplan-Meier (KM) analysis, and restricted cubic splines (RCS). The non-survivor group showed higher L/A ratios than survivors (1.04 ± 0.78 vs. 0.58 ± 0.29, p < 0.001), indicating a significant link between higher L/A ratios and mortality. Cox analysis identified the L/A ratio was significantly related to all-cause mortality both in-hospital (HR 2.033; 95% CI 1.576-2.624; p < 0.001) and one-year (HR 1.723; 95% CI 1.428-2.078; p < 0.001). The association between L/A ratio and mortality was non-linear and increasing. The KM survival curves demonstrated significantly poorer survival outcomes for the high L/A group compared to the low L/A group, a difference that was statistically validated by a significant log-rank test (log-rank p < 0.001). L/A ratio has a significant association with poor prognosis in patients with HF and CKD patients in a critical condition. This finding demonstrates that L/A ratio might be useful in identifying patients with HF and CKD at high risk of all-cause death. Further large-scale prospective studies are needed to verify these results and inform clinical decisions.

Evaluation of stem cell therapies in companion animal disease models: A concise review (2015-2023).

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [1]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [1]. The majority of studies were performed in dogs (n=28), with additional studies in horses (n=9) and cats (n=8). Disease models included those related to musculoskeletal disease (osteoarthritis, tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy) and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies is needed. Enhanced understanding of the temporal course of disease processes using advanced -omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem cell-based therapies could include use of stem-cell derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness.

The impact of comorbidities on prolonged mechanical ventilation in patients with chronic obstructive pulmonary disease

BackgroundIn patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, approximately 10% of them are considered to be at high risk for prolonged mechanical ventilation (PMV, > 21 days). PMV have been identified as independent predictors of unfavorable outcomes. Our previous study revealed that patients aged 70 years older and COPD severity were at a significantly higher risk for PMV. We aimed to analyze the impact of comorbidities and their associated risks in patients with COPD who require PMV.MethodsThe data used in this study was collected from Kaohsiung Medical University Hospital Research Database. The COPD subjects were the patients first diagnosed COPD (index date) between January 1, 2012 and December 31, 2020. The exclusion criteria were the patients with age less than 40 years, PMV before the index date or incomplete records. COPD and non-COPD patients, matched controls were used by applying the propensity score matching method.ResultsThere are 3,744 eligible patients with COPD in the study group. The study group had a rate of 1.6% (60 cases) patients with PMV. The adjusted HR of PMV was 2.21 (95% CI 1.44–3.40; P < 0.001) in the COPD patients than in non-COPD patients. Increased risks of PMV were found significantly for patients with diabetes mellitus (aHR 4.66; P < 0.001), hypertension (aHR 3.20; P = 0.004), dyslipidemia (aHR 3.02; P = 0.015), congestive heart failure (aHR 6.44; P < 0.001), coronary artery disease (aHR 3.11; P = 0.014), stroke (aHR 6.37; P < 0.001), chronic kidney disease (aHR 5.81 P < 0.001) and Dementia (aHR 5.78; P < 0.001).ConclusionsAge, gender, and comorbidities were identified as significantly higher risk factors for PMV occurrence in the COPD patients compared to the non-COPD patients. Beyond age, comorbidities also play a crucial role in PMV in COPD.

Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

BackgroundRenal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes.MethodsThis retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression.ResultsThe prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only.ConclusionsClinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

A comparison of two weaning strategies for non-invasive ventilation in chronic obstructive pulmonary disease patients with acute respiratory failure.

Non-Invasive Ventilation (NIV) is a crucial therapy for managing acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) with hypercapnic respiratory failure. Research has shown that NIV can decrease the rate of endotracheal intubation, length of hospital and Intensive Care Unit stays, and mortality. There are three main strategies for weaning patients off NIV: gradual reduction of NIV duration, gradual reduction of NIV pressure support, and immediate cessation of NIV. To compare the rate of successful withdrawal of COPD patients with acute hypercapnic respiratory failure, one group will use a stepwise reduction of duration of NIV, while the other group will use a stepwise reduction of pressure support. This study was a prospective observational study conducted at the Department of Pulmonary Medicine, Institute of Chest Diseases, Government Medical College, Kozhikode, over a period of 15months. The study population consisted of all COPD patients admitted to the Pulmonary Medicine ward or ICU with acute hypercapnic respiratory failure who were managed with non-invasive ventilation (NIV) without the need for invasive mechanical ventilation. Exclusions included patients requiring NIV for respiratory diseases other than COPD, those with significant comorbiditieslike acute left ventricular failure or fluid overload states as in chronic kidney disease, COVID-19 positive patients, patients on home NIV, patients who needed intubation early in treatment, and patients unwilling to participate in the study. The sample size was 140. Initial NIV settings and other management decisions prior to enrolment in the study were made by the treating physician according to standard protocols. Once weaning criteria were met (i.e., arterial pH > 7.35, SpO2 ≥ 90% at an FiO2 ≤ 50%, respiratory rate ≤ 25 breaths per minute, heart rate ≤ 120 beats per minute, systolic BP > 90mm Hg, and no signs of respiratory distress), patients were assigned to either group 1 or group 2 by purposive sampling. Group 1: stepwise reduction of duration of NIV use, with a reduction to 16h per day on day 1 of enrolment, 12h on day 2 (including 6-8h of nocturnal NIV), 6-8h on day 3, and NIV withdrawal on day 4. Group 2: stepwise reduction of pressure support, with pressure support reduced by 2-4cm every 4-6h until Inspiratory Positive Airway Pressure is < 8cm H2O and Expiratory Positive Airway Pressure is < 4cm H2O, followed by NIV withdrawal. The clinical outcome was classified as either improved or weaning failure. Improved was defined as an objective or subjective sense of improvement. Weaning failure was defined as the presence of any of the following: respiratory rate ≥ 25/minute or increase of ≥ 50% from baseline, heart rate ≥ 140/minute or increase of ≥ 20% from baseline, SpO2 ≤ 90% on FiO2 ≥ 50%, arterial pH ≤ 7.35, or respiratory distress. Data was collected using a pro forma that included demographic details, smoking status, GOLD COPD category, comorbidities, and vital signs. ABG parameters, NIV settings at the time of hospital admission, at the time of study enrolment, and 48h after weaning were also recorded. Independent sample t-test was used to test the statistical significance of the difference between means of variables between the two groups. Pearson Chi square test and Fisher's exact test were used to compare categorical variables between the groups. A p-value of < 0.05 was considered statistically significant. NIV was successfully withdrawn in 56/70 (80%) and 50/70 (71.4%) patients in Groups 1 and 2, respectively. This difference was not statistically significant. The length of hospital stay was longer in the stepwise reduction of duration group (Group 1), but this was not statistically significant. On comparison of two methods of NIV withdrawal, it was found that neither method is superior to the other in terms of weaning failure, intubation rates, and average length of hospital stay.

Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities.

Multiple common cardiovascular comorbidities produce coronary microvascular dysfunction. We previously observed in swine that a combination of diabetes mellitus (DM), high fat diet (HFD) and chronic kidney disease (CKD) induced systemic inflammation, increased oxidative stress and produced coronary endothelial dysfunction, altering control of coronary microvascular tone via loss of NO bioavailability, which was associated with an increase in circulating endothelin (ET). In the present study, we tested the hypotheses that (1) ROS scavenging and (2) ETA+B-receptor blockade improve myocardial oxygen delivery in the same female swine model. Healthy female swine on normal pig chow served as controls (Normal). Five months after induction of DM (streptozotocin, 3 × 50mgkg-1 i.v.), hypercholesterolemia (HFD) and CKD (renal embolization), swine were chronically instrumented and studied at rest and during exercise. Sustained hyperglycemia, hypercholesterolemia and renal dysfunction were accompanied by systemic inflammation and oxidative stress. In vivo ROS scavenging (TEMPOL + MPG) reduced myocardial oxygen delivery in DM + HFD + CKD swine, suggestive of a vasodilator influence of endogenous ROS, while it had no effect in Normal swine. In vitro wire myography revealed a vasodilator role for hydrogen peroxide (H2O2) in isolated small coronary artery segments from DM + HFD + CKD, but not Normal swine. Increased catalase activity and ceramide production in left ventricular myocardial tissue of DM + HFD + CKD swine further suggest that increased H2O2 acts as vasodilator ROS in the coronary microvasculature. Despite elevated ET-1 plasma levels in DM + HFD + CKD swine, ETA+B blockade did not affect myocardial oxygen delivery in Normal or DM + HFD + CKD swine. In conclusion, loss of NO bioavailability due to 5 months exposure to multiple comorbidities is partially compensated by increased H2O2-mediated coronary vasodilation.

Estimated Glomerular Filtration Rate Slope as an Endpoint in Cardiovascular Trials.

End stage kidney disease can be a slow process and it may be challenging to achieve required follow-up for sufficient events. Therefore, a surrogate kidney endpoint, such as estimated glomerular filtration rate (eGFR) slope maybe attractive to assess the kidney in cardiovascular trials, especially heart failure (HF). eGFR slope can generate informative results in a shorter follow-up period, has decreased risk of type-2 error, and is less sensitive to eGFR shifts compared with other surrogate kidney endpoints (eGFR decline≥40% or doubling creatinine). However, eGFR slope has its limitations with acute effects, heterogeneity in slope calculation/reporting, and deviations from linearity. eGFR slope is a kidney endpoint which may be well-suited for HF trials. Cross-collaborated guideline recommendations are needed to optimize the use of eGFR slope as a kidney endpoint in patients with HF.

Selection of Vascular Access for Hemodialysis in Elderly Patients with End Stage Kidney Disease

Selection of Vascular Access for Hemodialysis in Elderly Patients with End Stage Kidney Disease

Association between alcohol consumption and chronic kidney disease: a population-based survey.

Alcohol consumption is associated with both beneficial and harmful effects, and the role of alcohol consumption in chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the relationship between alcohol consumption and CKD or estimated glomerular filtration rate (eGFR). This study enrolled adults from the second Taiwanese Survey on Prevalences of Hypertension, Hyperglycemia, and Hyperlipidemia, conducted in 2007. Participants were categorized into frequent drinkers, occasional drinkers, and nondrinkers. The amount of alcohol consumption was assessed by standard drinks per week. The primary outcome was the presence of CKD, and the secondary outcome was the eGFR. Among 3967 participants with a mean age of 47.9years and a CKD prevalence of 11.7%, 13.8% were frequent drinkers, and 23.1% were occasional drinkers. The average amount of alcohol consumed was 3.3 drinks per week. Frequent drinkers (odds ratio [OR] 0.622, 95% confidence interval [CI] 0.443-0.874) and occasional drinkers (OR 0.597 95% CI 0.434-0.821) showed a lower prevalence of CKD than nondrinkers. Consumption of a larger number of standard drinks was associated with a lower prevalence of CKD (OR 0.872, 95% CI 0.781-0.975). Frequent drinkers and those who consumed a larger number of standard drinks per week showed higher eGFRs. Within the range of moderate alcohol intake, those who consumed more alcohol had a higher eGFR and reduced prevalence of CKD. The potentially harmful effects of heavy drinking should be taken into consideration, and alcohol intake should be limited to less than light to moderate levels.

IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via integrin α5/FAK in diabetic kidney disease.

Podocyte apoptosis or loss is the pivotal pathological characteristic of diabetic kidney disease (DKD). Insulin-like growth factor-binding protein 2 (IGFBP2) have a proinflammatory and proapoptotic effect on diseases. Previous studies have shown that serum IGFBP2 level significantly increased in DKD patients, but the precise mechanisms remain unclear. Here, we found that IGFBP2 levels obviously increased under a diabetic state and high glucose stimuli. Deficiency of IGFBP2 attenuated the urine protein, renal pathological injury and glomeruli hypertrophy of DKD mice induced by STZ, and knockdown or deletion of IGFBP2 alleviated podocytes apoptosis induced by high concentration of glucose or in DKD mouse. Furthermore, IGFBP2 facilitated apoptosis, which was characterized by increase in inflammation and oxidative stress, by binding with integrin α5 (ITGA5) of podocytes, and then activating the phosphorylation of focal adhesion kinase (FAK)-mediated mitochondrial injury, including membrane potential decreasing, ROS production increasing. Moreover, ITGA5 knockdown or FAK inhibition attenuated the podocyte apoptosis caused by high glucose or IGFBP2 overexpression. Taken together, these findings unveiled the insight mechanism that IGFBP2 increased podocyte apoptosis by mitochondrial injury via ITGA5/FAK phosphorylation pathway in DKD progression, and provided the potential therapeutic strategies for diabetic kidney disease.

A Thorough Literature Review of the Potential Benefits and Drawbacks of Long-Term Aspirin Use for the Primary Prevention of Cardiovascular Disease.

This article examines the role of aspirin in the primary prevention of cardiovascular disease. It highlights findings from major studies such as ASPREE (ASPirin in Reducing Events in the Elderly), ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events), and ASPREE-XT (ASPirin in Reducing Events in the Elderly - eXTension) , among others. The review focuses on aspirin's role in primary prevention for specific populations including older adults, diabetics, hypertension patients, rheumatoid arthritis patients, kidney transplant recipients, and those with specific lipoprotein(a) genotypes, among other groups. We review these studies, noting aspirin's role in reducing events such as myocardial infarctions and its potential for increasing bleeding risks. The review also considers the implications for patients with kidney disease, referencing the Chronic Renal Insufficiency Cohort (CRIC) study and the International Polycap Study-3 (TIPS-3) trial. Additionally, it addresses the shifting paradigms in guidelines from the US Preventive Services Task Force and other entities, underscoring the importance of individualized aspirin use by balancing benefits against bleeding risks. The article further explores the concept of platelet reactivity, discusses strategies for improving adherence to aspirin therapy, and identifies existing research gaps, such as the phenomenon of aspirin resistance. It concludes by suggesting potential areas for future investigation to enhance understanding and application of aspirin in cardiovascular disease prevention.

Unraveling the role of natriuretic peptide clearance receptor (NPR3) in glomerular diseases

Natriuretic peptides (NPs) are cardio-derived hormones that have a crucial role in maintaining cardiovascular homeostasis. Physiological effects of NPs are mediated by binding to natriuretic peptide receptors 1 and 2 (NPR1/2), whereas natriuretic peptide receptor 3 (NPR3) acts as a clearance receptor that removes NPs from the circulation. Mouse studies have shown that local NP-signaling in the kidney glomerulus is important for the maintenance of renal homeostasis. In this study we examined the expression of NPR3 in kidney tissue and explored its involvement in renal physiology and disease by generating podocyte-specific knockout mice (NPR3podKO) as well as by using an NPR3 inhibitor (NPR3i) in rodent models of kidney disease. NPR3 was highly expressed by podocytes. NPR3podKO animals showed no renal abnormalities under healthy conditions and responded similarly to nephrotoxic serum (NTS) induced glomerular injury. However, NPR3i showed reno-protective effects in the NTS-induced model evidenced by decreased glomerulosclerosis and reduced podocyte loss. In a ZSF1 rat model of diabetic kidney injury, therapy alone with NPR3i did not have beneficial effects on renal function/histology, but when combined with losartan (angiotensin receptor blocker), NPR3i potentiated its ameliorative effects on albuminuria. In conclusion, these results suggest that NPR3 may contribute to kidney disease progression.