Renal Parameters Research Articles

A prospective, multicentre study evaluating safety and efficacy of a fixed dose combination of Remogliflozin etabonate, Vildagliptin, and Metformin in Indian patients with type 2 diabetes mellitus (Triad-RMV)

AimsThe ICMR INDIAB-17 study revealed a diabetes prevalence of 11.4% in India, emphasizing the need for effective treatment for glycemic control. A Phase IV study was conducted to evaluate the safety and efficacy of a Fixed Dose Combination (FDC) of Remogliflozin, Metformin and Vildagliptin (RMV) in Type 2 Diabetes Mellitus (T2DM) patients uncontrolled on Metformin plus SGLT2 inhibitor or Metformin plus DPP4 inhibitor dual therapy.MethodsA total of 215 patients (mean age: 46.4 years; 64% male, 36% female) were enrolled across multiple centers in India. The study population included patients with a baseline HbA1c ≥ 8% at the time of screening. The primary objective was to assess safety based on treatment-emergent adverse events (TEAEs), while the secondary. aim was to evaluate effectiveness in terms of glycemic (HbA1c, fasting plasma glucose, postprandial glucose) and extra-glycemic measures (renal and lipid parameters). Statistical analysis was conducted using paired t-tests and the Wilcoxon signed-rank test for within-group comparisons, and the Bonferroni correction was applied to adjust for multiple comparisons. Effectiveness was evaluated at baseline, week 12, and week 24.ResultsThe study demonstrated statistically significant reductions in mean HbA1c levels from baseline to both week 12 and week 24 (p < 0.00001). At 24, weeks, 45.1% of patients achieved target HbA1c levels of ≤ 7%. Significant reduction was also observed in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels. Renal parameters remained stable or improved, and lipid profile parameters, including LDL-C and triglycerides, showed favorable changes. Adverse events of special interest, including hypoglycemia and urinary tract infections, were reported in 4.7% of patients, with no serious adverse event recorded.ConclusionsThe twice daily triple FDC of RMV was well tolerated, safe and effective in patients with Type 2 Diabetes Mellitus uncontrolled on dual drug therapy of Metformin plus SGLT2i or Metformin plus DPP4i. The treatment led to significant improvements in glycemic control and other metabolic parameters over 24 weeks, without compromising renal function or causing serious adverse events.Trial registrationCTRI, CTRI/2022/05/042581. Registered 17 May 2022, https//ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=68,757&EncHid=36127.16500&modid=1&compid=19.

Risk of renal dysfunction in patients with dengue fever: a case-control study

Dengue fever, a mosquito-borne infection, is typically caused by the Dengue virus, leading to various illnesses, including dengue fever and severe dengue fever. This study aims to investigate the outcome of dengue fever severity as renal dysfunction in patients. For this case-control study, blood samples of the patients (N=66), including 31 D-W (Dengue without warning signs), 20 D+W (Dengue with warning signs), and 15 SDF (Severe dengue fever), as well as controls (N=45) of same age groups, were obtained. The renal parameters were determined and statistically analyzed using a one-way ANOVA and chi-square/Fisher exact test. The intergroup comparison showed that phosphorous, calcium, and sodium presented a marked decrease (P &lt; 0.001) in dengue patient groups compared to controls. However, a significant increase (P &lt; 0.05) in chloride was indicated in dengue patient groups. Moreover, a prominent potassium reduction (P = 0.036) was observed in the dengue subjects group compared to controls. Among the renal parameters, creatinine presented a significant elevation (P &lt; 0.002) while uric acid was significantly (P = 0.004) dropped in dengue patients groups as compared to controls. This study's results suggest that dengue infection's severity may be associated with aberrant electrolyte imbalance and renal impairment. This study indicates that dengue affects normal kidney functions and harms the patients' health. Keywords: electrolytes; renal profile; dengue fever; severe dengue fever

Predictive Factors for Urinary Tract Infections in Patients with Type 2 Diabetes

Background/Objectives: Patients with diabetes (DM) are at an increased risk of infection, with urinary tract infections (UTIs) being common among individuals with type 2 DM (T2D). The aim of this study was to determine the prevalence and risk factors for UTIs among hospitalized T2D patients from Timișoara, Romania. Methods: The hospital records of 1139 T2D adult inpatients who were ordered to provide urine cultures during hospitalization were reviewed. Results: The prevalence of UTIs among T2D patients was 19.7%, and was higher in women than in men (27.5% vs. 9.8%, p &lt; 0.0001). Patients with UTIs presented a significantly older age, a longer duration of DM, a higher BMI, higher levels of HbA1c, higher renal function parameters, and more frequent DM-related complications and comorbidities than patients without UTIs. The following predictors were associated with increased UTI risk: age (OR = 1.05, p &lt; 0.0001); duration of DM (OR = 1.04, p &lt; 0.0001); BMI (OR = 1.05, p &lt; 0.0002); HbA1c levels (OR = 1.58, p &lt; 0.0001); female gender (OR = 3.47, p &lt; 0.0001); and the presence of retinopathy (OR = 1.47, p = 0.0118), chronic kidney disease (OR = 3.98, p &lt; 0.0001), distal symmetric polyneuropathy (OR = 7.65, p &lt; 0.0001), and cerebrovascular disease (OR = 4.88, p &lt; 0.0001). The use of sodium-glucose co-transporter 2 (SGLT2) inhibitors did not influence the risk of developing UTIs. Conclusions: T2D patients with prolonged disease duration, poor glycemic control, and DM-related complications are at an increased risk of developing UTIs. Therefore, a targeted therapeutic strategy addressing these risk factors is essential.

Higher plasma levels of endocannabinoids and analogues are correlated with a worse cardiometabolic profile in middle-aged adults.

The increase in age-related comorbidities, such as cardiometabolic diseases, has become a global health priority. There is a growing need to find new parameters capable of improving the detection of cardiometabolic risk factors, and circulating endocannabinoids (eCBs) are a promising tool in this context. Here, we aimed to investigate the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors in middle-aged adults. Seventy-two individuals (54% women; 53.6 ± 5.1 years old) were included in this study. Plasma levels of eCBs and analogues were determined using liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy X-ray absorptiometry. Cardiometabolic risk factors (i.e., glucose and lipid profile, blood pressure, liver and renal parameters, and gonadal hormones) were also assessed. The plasma levels of 1- and 2-arachidonylglycerol (1-AG&2-AG) were positively correlated with adiposity (all r ≥ 0.23, P < 0.05). Interestingly, the plasma levels of 1-AG&2-AG, arachidonoylethanolamide, and palmitoyl-ethanolamide were positively correlated with the homeostatic model assessment index - Insulin Resistance (HOMA-IR) (all r ≥ 0.32, P < 0.01). Our results also showed that high levels of 1-AG&2-AG, arachidonoylethanolamide, linoleoyl ethanolamide, and palmitoleoyl ethanolamide were correlated with poorer liver (all r ≥ 0.27, P < 0.05), kidney (all r ≥ 0.24, P < 0.05), and gonadal function parameters (testosterone: all r > 0.26, P < 0.05, SHBG: 1-AG&2-AG r=-0.33, P < 0.01). The plasma levels of some eCBs and analogues are correlated with a worse cardiometabolic profile in middle-aged adults.

Effects of Current Therapies on Disease Progression in Fabry Disease: A Narrative Review for Better Patient Management in Clinical Practice.

Fabry disease (FD) is a rare lysosomal storage disorder that is characterized by renal, neurological, and cardiovascular dysfunction. Four treatments are currently available for patients with FD; three enzyme replacement therapies (ERTs; agalsidase alfa, agalsidase beta, and pegunigalsidase alfa) and one pharmacological chaperone (migalastat). This review focuses on the evidence for the benefits of ERTs and migalastat, and provides an overview of their impact on disease manifestations and quality of life (QoL). Agalsidase beta is associated with renal, neurological, and cardiovascular benefits, and may prevent renal disease progression. Agalsidase alfa provides stabilizing effects across all main organ systems, although minor sex-specific differences exist in patients with more advanced baseline disease. The benefits of agalsidase alfa and agalsidase beta are similar but depend on the extent of baseline disease. Some data indicate that agalsidase beta may be preferable over the longer term. Both agalsidase alfa and agalsidase beta are associated with improved gastrointestinal and pain symptoms, as well as improved QoL. Patients with advanced end-organ damage tend not to respond as optimally to ERTs as those who initiate ERTs before irreversible organ fibrosis develops, highlighting the need for early treatment initiation. Migalastat, which is only approved for patients with amenable missense gene variants, generally stabilizes renal parameters and provides cardiovascular benefits. Migalastat also improves diarrhea and pain, and stabilizes QoL (although ERT may be more effective for pain management), but the neurological effects of migalastat have not been studied. Real-world data raise concerns about effective in vivo amenability of some genetic variants. Future studies with direct treatment comparisons in patients with FD are needed.

Therapeutic Potential of Silica Nanoparticles, Cisplatin, and Quercetin on Ovarian Cancer: In Vivo Model

The present study evaluated the effect of silica nanoparticles, quercetin, and cisplatin against ovarian cancer. Cisplatin is a potent antineoplastic agent but has greater toxicity against cancer. Quercetin is a powerful flavonoid with remarkable anti-cancer activity due to its anti-apoptotic nature. Forty female albino rats were randomly divided into eight groups, with five rats per group. Group 1 (G1) was normal control, G2 received Carboxymethylcellulose; G3 was the normal control and treated with quercetin, G4 was given silica nanoparticles, G5 was treated with cisplatin. G6 was the tumor control. Tumor induction was done by 7, 12-dimethylbenz (a) anthracene (DMBA), G7 was treated with quercetin-cisplatin-silica nanoparticles, and in G8 quercetin-cisplatin silica nanoparticles were used to treat the induced tumor. Chemically synthesized silica nanoparticles were characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and Fourier Transform Infrared (FTIR). After the treatment, animals were sacrificed and tested for biochemical and hormonal assays. G6 displayed increased body weight and a significant rise in CA125 as compared to G1. G6 also exhibited an altered hormonal profile, with a particular increase in estrogen, FSH, and testosterone, along with reduced LH and progesterone levels. Lipid profile, liver enzymes, and renal parameters (urea and creatinine) increased in G6, but G8 significantly ameliorated all damaging effects of DMBA as observed in G6. The current study revealed that silica nanoparticles combined with cisplatin and quercetin demonstrated greater protection against drastic changes induced by carcinogens in ovarian cancer mice models.

Safety Study of Fluralaner Solution on Poultry Red Mite: A Clinical Study Screening of the Optimal Dose and Focusing on Hepatic and Renal Parameters

Safety Study of Fluralaner Solution on Poultry Red Mite: A Clinical Study Screening of the Optimal Dose and Focusing on Hepatic and Renal Parameters

Role of Hepatic and Renal Biomarkers in Diagnosing Preeclampsia

Objective: The study aims to gain insight into the importance of hepatic and renal biochemical parameters AST, ALT, bilirubin, urea, creatinine, urinary protein to creatinine ratio, and novel marker cystatin C in the domain of preeclamptic patients. Methodology: This prospective cohort study was conducted in Central Park Medical College and Teaching Hospital Lahore from Sep 2023 to Apr 2024 on 300 subjects. Inclusion criteria were pregnant women over 18 years of age, gestational age of 20 weeks, and singleton pregnancy. Women with preexisting hypertension, kidney disease, or other diseases causing liver dysfunction were excluded. Blood and urine samples were collected to measure AST, ALT, bilirubin, urea, creatinine, urinary protein to creatinine ratio, and novel marker cystatin C and data was analysed using an independent t test and Chi-square test by SPSS version 26. Results: ALT, AST, and bilirubin levels were higher (45±12 p&lt;0.001, mean±SD 55±15 U/L, mean±SD: 1.5±0.4 mg/dL) in preeclamptic women. Creatinine, urine protein to creatinine ratio, and cystatin C (mean±SD: 1.0±0.2 mg/dl, mean±SD: 300±100 mg/g, p 1.2±0.3ng/mL) were raised in preeclamptic women as compared to the control group. Conclusions: Serum creatinine, urine protein/creatinine ratio, and cystatin C and creatinine were found in women with preeclampsia compared to women without preeclampsia.

Effects of iopromide contrast agents on kidney iNOS expression and tubular histopathology alterations

Contrast-induced acute kidney injury is a common complication marked by reduced kidney function within 48 hours of contrast administration. The aim of this study was to evaluate renal function, anatomy, and molecular changes at 24 hours, 48 hours, and 72 hours post-iodinated contrast media (ICM) administration. This true-experimental study used a post-test-only control group design. Rats underwent unilateral nephrectomy, followed by intravenous injection of ICM using iopromide 370 mg iodine/mL per rat at a dose of 231 mg iodine, and were then divided into four groups: control (C), rats terminated at 24 hours after iopromide administration (E24), rats terminated at 48 hours after iopromide administration (E48), and rats terminated at 72 hours (E72) after iopromide administration, with eight rats per group. Renal function (BUN and SCr levels) remained unchanged after 24, 48, and 72 hours of iopromide administration. Iopromide increased renal tubular damage, as shown by higher histopathological scores for loss of brush border and tubular necrosis, except for proteinaceous casts, where histopathological scores increase especially within the first 24 hours and decrease after 72 hours. Iopromide significantly altered iNOS expression in the glomerulus at 24 and 48 hours, and iNOS expression was decreased after 72 hours. iNOS expression in the intrarenal vascular and tubules was unaffected by iopromide administration. In conclusion, this study found no changes in renal function parameters, improvement in proteinaceous casts, and increased iNOS expression in the glomerulus, offering new insights into the effects of contrast on kidneys.

Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p &lt; 0.001). Here we report an assessment of laboratory parameters from this study. Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters. Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels. Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).

Blue toe syndrome - systemic cholesterol crystal embolism secondary to cardiovascular procedures: a forensic autopsy report of two cases.

Blue toe syndrome, also referred to as cholesterol crystal embolism is characterized by the distal embolization of cholesterol crystals originating from ruptured atherosclerotic plaques. This condition commonly arises in the context of cardiovascular procedures. Emboli from the thoracoabdominal aorta primarily affect the downstream extremities and intra-abdominal viscera, often resulting in fatal atheroembolic renal failure. Owing to its insidious and delayed onset, antemortem diagnosis of cholesterol crystal embolism is often underrecognized. Two cases of blue toe syndrome secondary to cardiovascular procedures are presented. In Case 1, the patient died 35 days after coronary angioplasty, whereas in Case 2, the patient developed toe necrosis 95 days after endovascular aortic repair, leading to progressive renal failure over the following five years. A comprehensive forensic autopsy included external examination, skin biopsy, histopathological examination of major organs, and serum biochemical evaluation of renal function parameters. Two cases of blue toe syndrome secondary to cardiovascular procedures are presented. In Case 1, the patient died 35 days after coronary angioplasty, whereas in Case 2, the patient developed toe necrosis 95 days after endovascular aortic repair, leading to progressive renal failure over the following five years. A comprehensive forensic autopsy included external examination, skin biopsy, histopathological examination of major organs, and serum biochemical evaluation of renal function parameters. This report underscores the importance of including systemic cholesterol crystal embolism in the differential diagnosis of blue toe syndrome, particularly in patients with a history of cardiovascular procedures. Fingertips serve as reliable indicators of impaired blood perfusion. To assess blue toe syndrome accurately, we highlight the value of focusing on the toe tips where cholesterol crystal embolism can be consistently detected.

Gait abnormalities and longitudinal fall risk in older patients with end-stage kidney disease and sarcopenia

BackgroundSarcopenia, gait disturbance, and intradialytic hypotension are among the various factors that contribute to fall risk. This study aimed to investigate the relationship between risk of sarcopenia, hemodialysis (HD) session, and long-term fall risk in older end-stage kidney disease (ESKD) patients by analyzing their spatiotemporal gait characteristics.MethodsWe recruited 22 non-demented patients aged ≥ 65 years who were undergoing maintenance HD. Participants were divided into two groups based on their SARC-F score (< 4 and ≥ 4) to identify those with higher and lower risk of sarcopenia. Demographics, comorbidities, and renal parameters were compared between groups. Inertial measurement unit-based technology equipped with triaxial accelerometry and gyroscope was used to evaluate gait characteristics. The gait task was assessed both before and after dialysis using the Timed-Up and Go (TUG) test and a 10-meter walking test at a regular pace. Essential gait parameters were thoroughly analyzed, including gait speed, stride time, stride length, double-support phase, stability, and symmetry. We investigated the interaction between the dialysis procedure and gait components. Outcome of interest was any occurrence of injurious fall during follow-up period. Logistic regression models were employed to examine the relationship between baseline gait markers and long-term fall risk.ResultsThe SARC-F ≥ 4 group showed various gait abnormalities, including longer TUG time, slower gait speed, longer stride time, shorter stride length, and longer double support time compared to counterpart (SARC-F < 4). After HD sessions, the SARC-F ≥ 4 group showed a 2.0-second decrease in TUG task time, an 8.0 cm/s increase in gait speed, an 11.6% lower stride time, and a 2.4% increase in gait symmetry with significant group-time interactions. Shorter stride length and longer double support time were associated with injurious falls during the two-year follow-up.ConclusionOur study demonstrated the utility of triaxial accelerometers in extracting gait characteristics in older HD patients. High-risk sarcopenia (SARC-F ≥ 4) was associated with various gait abnormalities, some of which partially improved after HD sessions. These gait abnormalities were predictive of future falls, highlighting their prognostic significance.

Abstract 4124931: Usefulness of the AHEAD Score for Prediction of All-cause Death in Patients With Acute and Chronic Coronary Syndromes

Background: The AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been introduced to predict all-cause death (ACD) in patients with heart failure. There is no information available on the utility of this score for the prediction of ACD in patients with coronary artery disease (CAD). Hypothesis: The AHEAD score may provide superior predictive value for ACD compared to the CHADS 2 score, which has been reported to be useful for predicting poor clinical outcomes in patients with acute (ACS) and chronic coronary syndromes (CCS). Methods: This retrospective multicenter cohort study analyzed data of the patients who underwent percutaneous coronary intervention for ACS or CCS between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The AHEAD score was calculated by assigning 1 point each for atrial fibrillation, hemoglobin &lt;13 mg/dL for men and &lt;12 mg/dL for women, age &gt;70 years, elevated creatinine levels (&gt;130 μmol/L), and diabetes mellitus. The CHADS 2 score was calculated as previously reported. The study endpoint was ACD. Results: In total, 9,033 patients were enrolled (median age, 72 years; 77% male; 3,920 with ACS and 5,113 with CCS). Higher AHEAD or CHADS 2 scores were significantly associated with a higher rate of left main disease or three-vessel disease in both patients with ACS and CCS. In addition, after accounting for multiple variables using Cox multivariate analysis, both the AHEAD (hazard ratio [HR], 1.83 [95% confidence interval, 1.63–2.06] for ACS and 1.66 [1.49–1.85] for CCS) and CHADS 2 scores (HR 1.27 [1.15–1.40] for ACS and 1.23 [1.12–1.35] for CCS) remained significantly associated with ACD. However, receiver operating characteristic curve analysis for predicting ACD revealed that the predictive value of the AHEAD score was significantly higher than that of the CHADS 2 score in both ACS and CCS (Figure). A significant difference was found in the rate of ACD among patients stratified by the AHEAD score in both groups (both P &lt;0.001). Conclusions: The AHEAD score had superior predictive value for ACD compared to the CHADS 2 score in patients with CAD, irrespective of ACS or CCS.

Evaluation of Severe ultrasound and gene diagnosis in cardiac index and shock patient index of shock patients.

The kidney is the most vulnerable organ in severe patients. In severe cases, the fatality rate of acute kidney damage is as high as 30% ∼ 60%. Severe ultrasound is a non-invasive method to evaluate renal blood flow. It can give a semi-quantitative score of renal blood flow and measure the Resistance Index (RI), which can reflect renal artery blood flow to a certain extent. There is little literature on hemodynamic regulation in septic shock patients, but almost no research report on the relationship between hemodynamics and RI exists. Therefore, this paper proposed the analysis of severe ultrasound and gene diagnosis in cardiac index and peripheral vascular RI of shock patients. This paper mainly expounded on detecting renal function parameters and RI in patients with viral shock to understand further the correlation between them and renal flow and RI. It could be seen from the experimental results that the P values before and after resuscitation in the two groups with and without elevated Cardiac Output (CO) were 0.41 and 0.12, respectively, which were more significant than 0.05. RI had no apparent relationship with CO, and RI could not be used as an evaluation index for patients with early septic shock.

EVALUATION OF SERUM PERIOSTIN AND PIIINP AS BIOMARKERS OF RENAL FIBROSIS AND FUNCTION DECLINE IN RENAL TRANSPLANT PATIENTS

This study aimed to evaluate the potential of serum periostin and N-terminal propeptide of type III procollagen (PIIINP) as biomarkers for predicting renal fibrosis and functional decline in renal transplant patients. We conducted a two-visit observational study among 86 renal allograft patients, reduced to 35 at the two-year follow-up due to the COVID-19 pandemic. Blood samples were collected at baseline and follow-up, while urine samples were collected only at follow-up. Serum levels of PIIINP and periostin were measured using ELISA kits, and various renal function parameters were assessed. Serum PIIINP levels showed a significant decrease over two years (p&lt;0.001, Wilcoxon test), while periostin levels significantly increased (p&lt;0.001, Wilcoxon test). These changes correlated with declines in renal function, as indicated by decreased serum albumin and creatinine clearance levels, and increased serum creatinine levels. Significant correlations were found between changes in PIIINP and creatinine clearance (Spearman coefficient = 0.352, p&lt;0.05), as well as between changes in periostin and creatinine clearance (Spearman coefficient = 0.626, p&lt;0.001). Our findings suggest that serum periostin and PIIINP levels are valuable biomarkers for assessing renal fibrosis and functional decline in renal transplant patients. These biomarkers may provide insights into disease progression and guide therapeutic interventions.

Network pharmacology combined with transcriptomics reveals that formononetin, a biologically component of Astragalus membranaceus (Fisch.) Bunge, inhibits the PI3K/AKT signaling pathway to improve chronic renal failure

Ethnopharmacological relevanceFormononetin (FMN), one of the main isoflavones isolated from Astragalus membranaceus (Fisch.) Bunge, has multiple pharmacological and renal-protective effects. Our previous study suggested FMN as a candidate compound for the treatment of chronic renal failure (CRF). However, the mechanism underlying the repressive effect of FMN on the development of CRF is still unknown. Aims of the studyTo investigate the protective effect of FMN on CRF using in vivo and in vitro models and elucidate the potential underlying mechanism. Materials and methodsAn in vivo model of adenine-induced CRF and an in vitro model of human proximal tubule epithelial cells (HK-2) stimulated with transforming growth factor (TGF)-β1 were used. Serum levels of renal function parameters and inflammatory cytokines were evaluated. Histological analysis was performed to determine the extent of renal injury and fibrosis. Network pharmacology and mRNA sequencing were used to explore the potential mechanism. PPI analysis and molecular docking were used to identify key targets. Polymerase chain reaction and western blotting were used to determine the mechanism underlying the effect of FMN on CRF. ResultsFMN decreased the levels of renal function biochemical markers, including serum creatinine, blood urea nitrogen, and 24 h urine protein content. Treatment with FMN improved renal tubule injury and extracellular matrix (ECM) components, including collagens I and III. In addition, FMN significantly inhibited epithelial-mesenchymal transition (EMT); decreased the expression of fibronectin, N-cadherin, vimentin, α-SMA, and TGF-β1; and restored the expression of E-cadherin. The effect of FMN on renal interstitial fibrosis contributed to decreasing the expression of PI3K, p-Akt, and interleukin (IL) 4, restoring the expression of nitric oxide synthase 3 (NOS3), and reducing the release of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-alpha), both in vivo and in vitro. FMN treatment improved renal function and deposition of ECM components, reduced protein levels of EMT markers in rat kidneys and HK-2 cells, decreased the release of inflammatory cytokines, and inhibited the PI3K/Akt signaling pathway. ConclusionsFMN treatment significantly reduced the release of inflammatory cytokines and inhibited the effects of the PI3K/Akt signaling pathway on the key targets IL-4 and NOS3. Our results suggest FMN therapy as a novel therapeutic strategy for treating CRF.

Correlation Between Renal Dimensions and Anthropometric Indices Using Computed Tomography in Adults Without Known Renal Disease: A Cross-Sectional Prospective Study

Background: Assessing renal volume as a potential indicator of renal function and related disorders is valuable for clinical decision-making. Computed tomography (CT) can accurately estimate actual kidney size. Objectives: This study aimed to evaluate the relationship between anthropometric parameters and renal dimensions measured by CT. Methods: Renal CT scan evaluations were performed on 634 individuals (308 males and 326 females) who had undergone abdominopelvic CT scans for indications unrelated to renal disease. Renal parameters, including length, width, depth, volume, and cortex length, were measured. Results: The mean age of participants was 53.5 ± 13.7 years (range: 18 - 86 years). Renal dimensions in males were larger than those in females. Additionally, the left kidney showed larger dimensions than the right kidney in both genders. Renal dimensions increased with age initially, but began to decrease after the sixth decade of life. A significant negative correlation was found between age and renal length, cortex, and left renal volume. In contrast, a significant positive correlation was observed between weight and both renal depth, length, volume, and left renal cortex, as well as between height and both renal length and volume on both sides. All dimensions except renal length were greater with increasing Body Mass Index (BMI). Conclusions: The results indicate a significant correlation between kidney dimensions and various anthropometric factors such as age, weight, height, and BMI. These findings provide valuable insights into kidney dimensions measured on CT scans, potentially aiding in the diagnosis and treatment of kidney diseases.

Association of cytochrome P450 CYP2C9 (rs1057910) gene polymorphism and ibuprofen response in preterm neonates diagnosed with patent ductus arteriosus

Background Patent ductus arteriosus (PDA) closure is one of the most significant changes necessary to transition to extrauterine life. The failure of closure in preterm infants has been associated with a variety of complications. Aim and objectives This study aim to investigate the correlation between cytochrome P450 CYP2C9 gene polymorphism and the response to ibuprofen treatment in preterm neonates with PDA. Subjects and methods This prospective study was conducted on 64 preterm neonates with patent ductus arteriosus (hsPDA). The neonates were treated with ibuprofen and diagnosed using clinical and echocardiographic examinations. The study was carried out at the Neonatal Intensive Care Unit (NICU), Pediatric Department, Kasr Alainy and ElMounira Pediatric Hospitals, Cairo University, in June 2018. Results A statistically significant difference in respiratory rate was observed between both groups ( p = 0.047). Additionally, there was a significant difference in the duration of treatment with ibuprofen ( p = 0.021). Treatment with ibuprofen had no impact on renal function parameters. The platelet count decreased after treatment with no statistical difference. Conclusion Use of Oral ibuprofen is a highly effective treatment for HsPDA in preterm neonates, demonstrating a remarkable success rate of 92.2% and fewer adverse effects. Whilst no correlation between the CYP2C9 (rs1057910) gene polymorphism and the efficacy of oral ibuprofen response, Other factors affecting the response of oral ibuprofen and subsequent PDA closure include gestational age, birth weight, Apgar score at 5 min, ductal diameter, RDS, and sepsis.

A clinical study on the efficacy and safety of poly-herbal formulation in managing functional dyspepsia

IntroductionFunctional dyspepsia is a common condition that affects millions of people worldwide. It is characterized by symptoms such as abdominal discomfort, bloating, and nausea, which can significantly impact a person's quality of life. While there are several pharmaceutical treatments available, many individuals are turning to herbal remedies as a safer and more natural alternative. This clinical study aimed to evaluate the efficacy and safety of poly-herbal formulation (PHF), marketed under brand names like Dizester® Herbal, Great Day®, etc. in patients suffering from functional dyspepsia compared to Pantoprazole, a commonly used pharmaceutical treatment. Materials & MethodsThe study included 80 patients, with 40 patients in each treatment arm. The primary objective was to assess the improvement in symptoms using various questionnaires at All India Institute of Medical Science Bhubaneswar, including the Reflux Disease Questionnaire, Short-Form Leeds Dyspepsia Questionnaire, GERD-Health Related Quality of Life Questionnaire, visual analogue scale (VAS) for pain, and Investigator's Symptomatic Assessment. The secondary objective was to evaluate the safety of PHF by assessing liver and renal function parameters and hemogram. Results & discussionThe results showed significant improvement in symptoms of GERD in the PHF group, which was comparable to the Pantoprazole group. The burning feeling behind the breastbone, pain behind the breastbone, burning feeling in the center of the upper stomach, acid taste in the mouth, and unpleasant movement of material upwards towards the mouth improved significantly from the beginning of the study to the follow-up visits. The mean VAS score reduced by 71.5 % in the PHF arm and 67.85 % in the Pantoprazole arm. Additionally, the study found no abnormal elevations in liver and renal function parameters in blood or any abnormal changes in hemogram, indicating the safety for use in patients with functional dyspepsia. Since the synthetic anti-dyspeptic drugs like proton pump inhibitors are known to have adverse effects, this natural alternative PHF shows promising results in a safer way. ConclusionIn conclusion, this study provides evidence for the efficacy and safety of PHF in improving symptoms of functional dyspepsia. The use of synthetic anti-dyspeptic medications has been associated with the occurrence of undesirable effects. In light of this, PHF has demonstrated encouraging outcomes in a manner that is considered safer.

Long-Term Cardiovascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a promising class of medications for type 2 diabetes (T2D) management. While their glucose-lowering effects are well-established, their long-term impact on cardiovascular outcomes remains a subject of ongoing research and debate. This systematic review aims to assess the long-term cardiovascular effects of GLP-1 RAs in adults with T2D compared to placebo, standard care, or other glucose-lowering medications. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies published from database inception to April 2024. Two independent reviewers screened the studies and extracted the data. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Secondary outcomes included individual components of MACE, hospitalization for heart failure, and all-cause mortality. We included 15 studies (eight RCTs and seven observational studies) involving over 180,000 participants. GLP-1 RAs were associated with a significant reduction in MACE compared to placebo or standard care (risk ratio: 0.88, 95% CI: 0.82-0.94, p<0.001). GLP-1 RAs also demonstrated superior cardiovascular protection compared to DPP-4 inhibitors and sulfonylureas. The benefits were particularly pronounced in reducing the risk of stroke and MI. Notably, some studies found larger cardiovascular benefits in frail patients. The effects on heart failure outcomes were mixed, with potential attenuated benefits in patients with baseline heart failure. GLP-1 RAs also showed promising effects on renal outcomes and metabolic parameters. The quality of evidence ranged from moderate to high across outcomes. This systematic review provides strong evidence that GLP-1 RAs offer significant cardiovascular benefits in adults with T2D, particularly in reducing MACE, stroke, and MI. The findings support current guidelines recommending GLP-1 RAs as preferred agents in patients with established cardiovascular disease or high cardiovascular risk. However, the variability in effects across different patient subgroups underscores the need for personalized treatment approaches. Future research should focus on head-to-head comparisons between different GLP-1 RAs, long-term follow-up studies, and investigation of combination therapies to further optimize the use of these agents in clinical practice.