Increase In Creatinine Levels Research Articles

Effects of Helianthus annuus seeds on antioxidants, lipid profile and serum urea and creatinine in obesity induced rats using high fat diet

High-fat diets have been strongly associated with common metabolic diseases. Clinical practices often link these diseases, such as hyperlipidemia and oxidative stress resulting from the accumulation of reactive oxygen species, to severe conditions like cancer, diabetes, atherosclerosis, and cardiovascular diseases. Managing these conditions is often financially demanding. Helianthus annuus seeds, known to be non-toxic even at doses greater than 5000mg/kg in rats, with an LD50 greater than 5000mg/kg, has demonstrated efficacy in reducing elevated blood sugar levels and BMI in both animal and human studies. Therefore, further research is needed to explore the potential effects of sunflower seeds on antioxidants, lipid profiles, and serum urea and creatinine levels in rats induced with obesity using a high-fat diet. In this study, overnight fasting blood samples were collected to conduct lipid profile tests (HDL, LDL, VLDL, and triglycerides). These tests utilized a photometric system with procedures derived from the Diasys-G Emmany kit and the measurement and precipitation method. The modified Jaffe technique for in-vitro measurement of creatinine in serum was employed to measure urea and creatinine levels. The experiment involved 27 Wistar rats weighing between 350 and 400 grams, randomly divided into 9 groups, with 3 rats in each group. Group 1 served as the control, while groups 2 to 9 were subjected to various conditions: high-fat diets alone for 6 weeks (group 2), high-fat diets with high (5000mg/kg body weight), medium (3000 mg/kg body weight), or low (2000 mg / kg body weight) doses of Helianthus annuus seeds powder for 6 weeks (groups 3, 4, and 5, respectively). Additionally, there were variations in duration and doses in groups 6 to 9, where rats were fed high-fat diets 20 g/ kg / day /rats for 5 weeks and then supplemented with Helianthus annuus seeds powder (5000 mg / kg, 3000 mg / kg and 2000 mg / kg per rat for group 6,7,8 or Metformin 70 mg / kg per rat for group 9) for 1 week. The results revealed a significant (P < 0.05) increase in serum cholesterol, triglyceride, and low-density lipoprotein (LDL) levels in rats across all groups compared to the control. However, all groups supplemented with Helianthus annuus seeds alongside high-fat diets displayed a significantly increased HDL level (P < 0.05) compared to rats fed only high-fat diet alone. Creatinine levels were significantly increased in all Helianthus annuus seeds -supplemented groups compared to the high-fat diet alone, while urea levels showed no significant differences among the groups. Furthermore, rats in all Helianthus annuus seeds -supplemented groups alongside high-fat diets demonstrated a significantly increased glutathione reductase activity (P < 0.05) compared to the control and high-fat diet alone. The study indicated that sunflower seeds significantly bolster antioxidant protection, elevate HDL levels, and increase creatinine levels in rats fed high-fat diets, suggesting potential beneficial effects in mitigating the adverse impacts of high-fat diets on health parameters.

Diagnostic efficacy of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for early detection of acute kidney injury in dogs with leptospirosis or babesiosis.

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3mg/dL within 48h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice.

#474 Features of the functional state of the kidney in patients with chronic heart failure with metabolic syndrome

Abstract Background and Aims to study the features of the functional state of the kidneys in patients with chronic heart failure with intermediate ejection fraction, depending on the representation of components of metabolic syndrome Method To achieve the objectives, 197 male patients with chronic heart failure (CHF) of ischemic origin II - III functional class (FC) according to NYHA, aged 40-60 years with a history of myocardial infarction of 6 months, were examined. up to 5 years. Depending on the presence of MS components, 3 groups of patients were identified: group I (n = 70), patients without MS (CHF FC II -38, CHF FC III - 32 patients); Group II (n = 67) patients with various combinations of dyslipidemia (HDL-C &amp;lt;1.03 mmol/l; LDL-C &amp;gt;3.0 mmol/l) with AO, hypertension and HTG (CHF FC II -35, CHF FC III - 32 patients); Group III (n = 60) patients with various combinations of dyslipoproteinemia (DLP) and type 2 diabetes mellitus (DM2) with AO, hypertension and HTG (CHF FC II -26, CHF FC III - 34 patients). When diagnosing MS, the International Diabetes Federation diagnostic criteria for MS were used (IDF, 2009). The study of the functional state of the kidneys included determination of the level of serum creatinine, urinary albumin excretion (determination of microalbuminuria (MAU ≥300 mg/l), glomerular filtration rate (GFR), calculated using the GFR EPI formula. Results when studying the parameters of the functional state of the kidneys in patients with CHF HFmrEF group 1, MAU was identified in 10 patients (35.7%) out of 28. Serum creatinine clearance in this group was 89.0 ± 8.49 μmol /l, and the GFR level was 88.58 ± 8.36 ml/min. With the development of MS in group II patients, 16 out of 28 patients had MAU (53.6%). A decrease in GFR was also found by 11.3% ( P &amp;lt; 0.05) with an increase in serum creatinine levels by 12.7% (P &amp;lt; 0.01), in contrast to the data from group I of the study. Further analysis of the parameters of renal function in group III of CHF HFmrEF revealed a significant decrease in GFR (by 23.0%; P &amp;lt; 0.01) with a significant increase in blood creatinine levels (by 21.8%; P &amp;lt; 0.01) in relation to the data Group I. Also in group III of patients with CHF and MS (+DM2 ), microalbuminuria was detected in 24 patients (85.7%) out of 32 . When comparing indicators of renal function between study groups II and III, there was a significant difference in the level of blood creatinine clearance and glomerular filtration rate by 11.3% and 10.1% (P &amp;lt; 0.05), respectively. Conclusion MS in patients with CHF HFmrEF aggravates renal dysfunction, which developed as one of the main pathogenetic links of CHF. Evidence of the importance of MS in the nature of the clinical manifestations of CHF HFmrEF is the established dependence of the identified disorders on the severity of MS.

#2945 Albuminuria – a neglected cause of referral to Nephrology

Abstract Background and Aims Albuminuria has been a recognized marker of cardiovascular risk for several years. Since 2012, the KDIGO guidelines have included this marker in the definition of chronic kidney disease (CKD), regardless of the Glomerular Filtration Rate (GFR). Despite this, a decade after, albuminuria is rarely researched as a marker of kidney disease, especially in Primary Health Care. We aim to assess the percentage of patients referred from the Health Centre to the Nephrology consultation of a district hospital, with an indication of the albuminuria value and also which percentage considered it the main cause of referral. Method Retrospective observational study of all patients referred from the Health Centre to the Nephrology consultation, from January 2022 to May 2023. A statistical analysis was carried out using Microsoft Excel 2016 (Microsoft ™). Results A total of 248 patients were referred and accepted for the nephrology consultation, 52.4% female, average age 74.8 years, with almost 80% (n = 198) of patients aged 65 or over and 41.5% (n = 103) aged over 80. The reasons for referral were: 53.6% due to an increase in creatinine levels; 21% due to imaging alterations; 19% due to a reduction in GFR and only 6.4% (16 patients) due to a urinary alteration, which included the presence of albuminuria. Only 26.2% (n = 65) of the patients referred had mentioned the value of albuminuria, and of these, around 73% (n = 49) already had an albuminuria value greater than or equal to 30 mg/dL; however, in only 14 of these patients (5.6% of all the patients referred) was albuminuria the main reason for the referral. Of the 49 patients with albuminuria: 44 patients (89.8%) had cardiovascular disease (around 98% with hypertension and around 28% with HF) and 34 patients (69.4%) had diabetes; 32 patients (65.3%) were medicated with ACE inhibitors/ARBs and only 13 patients (26.5%) were medicated with iSGLT2. The percentages of use of ACEIs/ARAs and iSGLT2 remain the same when analyzing the 14 patients who were referred for albuminuria. Conclusion Albuminuria remains an overlooked marker of CKD despite being an early marker and for which there are several interventions that seem to prevent the worsening and progression of CKD. It is imperative to train doctors, especially family doctors, in the early diagnosis of CKD, particularly in the presence of albuminuria and to implement measures to control it.

#259 Predictive capacity and comparison of new biomarkers for AKI in patients undergoing non-cardiac surgery

Abstract Background and Aims The diagnosis of AKI, according to the KDIGO guidelines, is still based on a tangible increase in serum creatinine which, however, cannot be detected until 24-48 hours after renal damage. Unfortunately, it has not been possible to identify among the various new biomarkers the one that is potentially able to detect AKI early, to intervene promptly to preserve renal function. The aim of this study was to analyze, in a population of patients undergoing major non-cardiac surgery, the most recent urinary biomarkers to evaluate their predictive potential for AKI and compare them with creatinine levels. Method 22 patients (18 males, 4 females) with an average age of 76 (67-85) years were enrolled for the study. 22 urine samples were analyzed by: Results Carrying out a correlation between the new biomarkers for AKI (Nephrocheck, NGALds and SEPP1) with creatinine levels at different times (pre-operative, post-operative and 24 h post-operative) shows a significant correlation only with NGALds (respectively p = 0.017, p = 0.035 and p = 0.012) (Table). Subdividing patients based on the increase in creatinine levels from pre-operation to 24 hours post-operation, the only biomarker that showed an increase in values ​​was NGALds, while the others showed levels discordant with creatinine. Conclusion By analyzing the new biomarkers and comparing them with the creatinine data, it emerged that NGALds alone significantly correlated with the latter at different times. The other urinary biomarkers (Nephrocheck and SEPP1) showed no correlation with creatinine levels. Based on this outcome, it could be assumed that NGALds is the biomarker which, due to its characteristics already stated in numerous studies and its correlation with creatinine, could be used and replace the latter as an early biomarker of AKI.

#1312 Warfarin-related nephropathy in two patients with mechanical valves

Abstract Background and Aims Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical valves required long-term anticoagulant therapy, and warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical valves constitute a special group among the entire anticoagulant population. Method The present study recorded two patients receiving warfarin therapy for mechanical valve presented to the hospital with gross hematuria and progressive creatinine levels. Results The first patient was a 56-year-old female, who had previously undergone mechanical aortic valve replacement surgery nine months ago and was prescribed warfarin, was admitted to the hospital due to the occurrence of gross hematuria six days before hospitalization. Additionally, her creatinine levels exhibited a rapid increase from 120.5umol/L to 207.5 μmol/L within three days. Laboratory analysis revealed a creatinine level of 167.8 μmol/L, albumin level of 39.6 g/L, and an INR value of 2.08. The urinary test results indicated the presence of urinary protein (+) and urinary occult blood (3+). The quantification of urinary protein over a 24-hour period was measured at 0.69 g. The immunoglobulin, complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. The second patient was a 63-year-old male, who has been diagnosed with hypertension for the twenty years, underwent Bentall+Sun's surgery for type A aortic dissection five years ago. Following the surgery, the patient was prescribed warfarin. The patient was admitted to the hospital due to persistent gross hematuria for a duration of twenty days and an increase in creatinine levels. Upon admission, laboratory analysis revealed a creatinine level of 169.9μmol/L (which was within the normal range one year ago), and an INR of 2.69. The urinary test indicated the presence of urinary protein (2+) and urinary occult blood (3+). Urinary protein quantification was 3.06 g/24 hours. The serum IgA level was measured at 4.55 g/L (normal range: 1.0-4.2 g/L). The complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. Pathology of two patients all showed red blood casts and tubular injury consistent with ARN and underlying IgA nephropathy (Fig. 1). The two patients was administered a daily dosage of 20 mg of prednisolone and an oral dosage of 50 mg of cyclophosphamide every other day. During a subsequent follow-up after a two-month period, the first patient's creatinine had decreased to 109.2μmol/L, and the urine protein quantification was recorded as 119.7 mg/24 hours. The second patient's creatinine had decreased to 159.2 μmol/L, and the quantification of urine protein was recorded at 310 mg/24 hours. Conclusion Clinicians should maintain a state of increased alertness with regards to the potential occurrence of WRN who exhibit hematuria and elevated creatinine levels while on warfarin therapy, even if their INR remains within the normal range. Considering most patents of WRN have an underlying glomerular disease (mostly IgA nephropathy), the use of steroids and immunosuppressive drugs may appear to be an attractive option, particularly in patients who are unable to replace warfarin with direct oral anticoagulants (NOACs).

#210 Effects of serum magnesium level on kidney disease progression and major cardiovascular outcome in patients with chronic kidney disease

Abstract Background and Aims Magnesium is known for its anti-inflammatory, anti-apoptotic, and anti-oxidative effects, potentially inhibiting renal fibrosis. Additionally, it is believed that magnesium can inhibit vascular calcification, potentially improving cardiovascular outcomes. However, this remains a topic of controversy. This study aims to investigate the association between serum magnesium levels and CKD progression as well as cardiovascular outcomes. Method We analyzed 1,893 patients from The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD), which is a prospective cohort study. These patients were categorized into three groups based on their baseline magnesium levels: Mg1 (hypomagnesemia, &amp;lt;1.8 mg/dL), Mg2 (normomagnesemia, 1.8-2.4 mg/dL), and Mg3 (hypermagnesemia, &amp;gt;2.4 mg/dL). The primary outcome was defined as meeting one or more of the following criteria during the follow-up period: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate. The secondary outcome was a composite of major adverse cardiovascular events (MACEs). We used Cox proportional hazard regression model. Results A total of 673 patients (35.6%) experienced the composite renal outcome. The Mg1 group showed significantly increased adverse renal outcomes compared to the Mg2 group (HR, 1.885; 95% CI, 1.137-3.124; p = 0.013), however, Mg3 group did not show a significant difference (HR, 0.927; 95% CI, 0.783-1.097; p = 0.379). The composite cardiovascular outcome occurred in 138 patients (7.3%). The risk of composite cardiovascular outcomes significantly increased in the Mg1 group compared to the Mg2 group (HR 3.472; 95% CI, 1.492-8.076; p = 0.003). However, we observed no statistically significant differences in the Mg3 group (HR 1.021; 95% CI, 0.689; p = 0.913). The cubic spline curves demonstrated a U-shaped association between serum magnesium levels and both renal and cardiovascular outcomes. Conclusion Hypomagnesemia is associated with the progression of renal disease and a significant increase in MACEs. Beyond a certain level, hypermagnesemia may also be associated with worsening renal and cardiovascular outcomes.

Effect of three oral pathogens on the TMA-TMAO metabolic pathway

BackgroundTrimethylamine-N-oxide (TMAO) is produced by hepatic flavin-containing monooxygenase 3 (FMO3) from trimethylamine (TMA). High TMAO level is a biomarker of cardiovascular diseases and metabolic disorders, and it also affects periodontitis through interactions with the gastrointestinal microbiome. While recent findings indicate that periodontitis may alter systemic TMAO levels, the specific mechanisms linking these changes and particular oral pathogens require further clarification.MethodsIn this study, we established a C57BL/6J male mouse model by orally administering Porphyromonas gingivalis (P. gingivalis, Pg), Fusobacterium nucleatum (F. nucleatum, Fn), Streptococcus mutans (S. mutans, Sm) and PBS was used as a control. We conducted LC-MS/MS analysis to quantify the concentrations of TMAO and its precursors in the plasma and cecal contents of mice. The diversity and composition of the gut microbiome were analyzed using 16S rRNA sequencing. TMAO-related lipid metabolism and enzymes in the intestines and liver were assessed by qPCR and ELISA methods. We further explored the effect of Pg on FMO3 expression and lipid molecules in HepG2 cells by stimulating the cells with Pg-LPS in vitro.ResultsThe three oral pathogenic bacteria were orally administered to the mice for 5 weeks. The Pg group showed a marked increase in plasma TMAO, betaine, and creatinine levels, whereas no significant differences were observed in the gut TMAO level among the four groups. Further analysis showed similar diversity and composition in the gut microbiomes of both the Pg and Fn groups, which were different from the Sm and control groups. The profiles of TMA-TMAO pathway-related genera and gut enzymes were not significantly different among all groups. The Pg group showed significantly higher liver FMO3 levels and elevated lipid factors (IL-6, TG, TC, and NEFA) in contrast to the other groups. In vitro experiments confirmed that stimulation of HepG2 cells with Pg-LPS upregulated the expression of FMO3 and increased the lipid factors TC, TG, and IL-6.ConclusionThis study conclusively demonstrates that Pg, compared to Fn and Sm, plays a critical role in elevating plasma TMAO levels and significantly influences the TMA-TMAO pathway, primarily by modulating the expression of hepatic FMO3 and directly impacting hepatic lipid metabolism.

High body mass index and triglyceride levels at health checkups increase the risk of new-onset chronic kidney disease and worsening renal function: the TAMA MED Project-CKD.

Health checkups are important in patients with chronic kidney disease (CKD), which is not easily accompanied by subjective symptoms. CKD can be caused or aggravated by factors that have not yet been identified. This retrospective cohort study included 7 483 patients who underwent specific annual health checkups at a medical institution in Tama City, did not have CKD in 2012, and continued to undergo checkups (aged 40-74years). We examined the risk factors for new-onset CKD and 1.5-fold increase in serum creatinine levels among laboratory values from 2012 to 2020. Age, body mass index (BMI), triglyceride levels, atrial fibrillation, and medication for hypertension (HT) and diabetes mellitus were independent risk factors for proteinuria, whereas current smoking, BMI, systolic blood pressure (SBP), and medication for HT were independent risk factors for estimated glomerular filtration rate < 60mL/min/1.73m2. SBP, triglyceride levels and medication for HT were risk factors for a 1.5-fold increase in serum creatinine levels during course of the study. The cut-off values of BMI for eGFR < 60mL/min/1.73m2 were 22.2 (men 24.7, women 22.1) kg/m2 and fasting triglyceride levels for a 1.5-fold increase in serum creatinine level were 171 (men 247, women 170) mg/dL, respectively. Health checkups provide information to prevent new-onset CKD and worsening of renal function. It is necessary to increase the rate of health checkups and visits to medical institutions after health checkups as well as to use these results for health guidance.

A Comprehensive Pathophysiologic, Histologic, and Biochemical Analysis of Buthus paris (C. L. Koch, 1839) Venom.

Buthus species, including B paris, are classified as one of the most dangerous scorpion genera in Morocco, implicated in several cases of human death. Our objective is to characterize, for the first time, the toxicity and histopathologic and biochemical impacts of B paris venom. We investigated the experimental pathophysiology of B paris venom by examining histologic changes in vital organs (heart, kidneys, liver, and lungs) and assessing biochemical enzymatic markers (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase, urea, and creatinine) in mice injected subcutaneously with 2 doses of 400 and 450 mg·kg-1. Our results showed that the subcutaneous median lethal dose of B paris venom was around 0.52 mg·kg-1. Histologic findings revealed significant tissue damage in the previously mentioned vital organs, confirmed through biochemical analysis indicating impaired heart and liver functions. Additionally, an increase in urea, creatinine, and glucose levels occurred following B paris venom injection. Our findings show that B paris venom exhibits a high level of experimental toxicity. These results highlight the potentially lethal nature of this venom and emphasize the potential medical importance of this species.

Incidental Finding of Deranged Renal Function in Elderly Patients Presenting with Fractures in a Tertiary Care Hospital

Objective: To determine the incidental rate of renal impairment among elderly women with fractures who reported to the Orthopaedic OPD at a tertiary care Hospital. Methodology: This prospective cohort study was done at Orthopaedic department and OPD Fauji Foundation Hospital, Rawalpindi during a period of one year from March 2022 to February 2023. A total of 147 females aged &gt;60 years presented with Hip fractures, surgically managed and who had history of normal pre-fracture renal function were included. A 5ml blood sample was obtained and sent to the Hospital diagnostic laboratory to evaluate the renal profile, serum calcium and vitamin D levels. All the information was recorded via pre-structured study proforma. Results: The study enrolled 147 elderly participants with an average age of 66.82 years. Among the participants, 24 patients (16.3%) experienced Acute Kidney Injury (AKI), with 9.5% having stage-I AKI, 4.8% with stage II AKI, and 2.0% with stage III AKI. Before sustaining the hip fracture, the mean serum creatinine level was 67.04 µmol/L, and following the fracture, it increased to 81.95 µmol/L (p-value &lt; 0.0001). The severity of AKI did not exhibit a statistically significant correlation with the age of the patients. However, there was a statistically significant increase in serum creatinine levels among patients based on the duration of their fractures (p-value &lt; 0.001). Conclusion: The incidence of Acute Kidney Injury (AKI) in elderly patients following hip fractures was found to be 16.3%, with varying stages of severity.

Successful chimney endovascular aortic repair with reconstruction of three visceral branches for huge saccular juxtarenal abdominal aortic aneurysm after trans-thoracoabdominal esophagectomy

BackgroundConventional graft replacement for a juxtarenal abdominal aortic aneurysm (JRAAA) remains challenging for high-risk patients since it often requires the reconstruction of some visceral arteries.Case PresentationA 76-year-old woman was diagnosed with an 87 × 48 mm saccular JRAAA. Open graft replacement was contraindicated because of frailty and a past history of trans-thoracoabdominal esophagectomy. Chimney endovascular aortic repair (ChEVAR) with three chimney endografts was successfully performed without any endoleaks, and each visceral circulation was kept intact. The patient was discharged uneventfully on postoperative day 8. Significant shrinkage of the aneurysmal sac and preservation of flow through each chimney graft were observed on computed tomography 6 months postoperatively, with no significant increase in serum creatinine levels on laboratory testing.ConclusionsChEVAR can be a useful surgical option instead of conventional operations, especially for high-risk cases.

Fermented Unripe Plantain Juice Ameliorates Diclofenac-Induced Hepatic and Renal Dysfunction in Wistar Rats

Diclofenac administration has been associated with several health problems in human including gastrointestinal tract problems, renal toxicity, among others. Several medicinal plants are been used locally for the treatment of several diseases. The aim of this study was to investigate the potential of fermented unripe plantain juice (FUPJ) in ameliorating diclofenac-induced ulcer and renal dysfunction. Twenty (20) healthy adult Wister rats weighing between 110g to 200g were randomly divided into four groups of five rats each. Group I served as control, received distilled water and feeds, Group 2 received 10mg/kg body weight of diclofenac only, Group 3 received 10mg/kg body weight of diclofenac only and post treated with 200mg/kg body weight of FUPJ and Group 4 received 200mg/kg body weight of FUPJ. The diclofenac was administered IP and fermented unripe plantain extract was administered orally for fourteen (14) days. The results showed that diclofenac administration caused a significant increase (p&lt;0.05) in serum levels of creatinine and a significant decrease (p&lt;0.05) in antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) compared to the control group. Additionally, diclofenac administration caused ulceration in the gastric mucosa. However, treatment with FUPJ significantly reduced (p&lt;0.05) the levels of creatinine, urea, and MDA and increased (p&lt;0.05) the levels of antioxidant enzymes in a dose-dependent manner. The highest dose of FUPJ (200mg/kg) showed the most significant reduction in the levels of the tested parameters and prevented the gastric mucosal ulceration. In conclusion, FUPJ has the potential to ameliorate diclofenac-induced ulcer and renal dysfunction through its antioxidant and anti-inflammatory properties.

Silymarin and MSC-exosomes ameliorate thioacetamide-evoked renal fibrosis by inhibiting TGF-β/SMAD pathway in rats

BackgroundTGF-β1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis.AimThis study aimed to evaluate the kidney protective potentials of silymarin (SM) and exosomes of mesenchymal stem cells against the nephrotoxin thioacetamide (TAA) in rats.Methods32 female rats were randomly assigned into four groups: the control group, the TAA group, the TAA + SM group, and the TAA + Exosomes group. The kidney homogenates from all groups were examined for expression levels of TGF-β receptors I and II using real-time PCR, expression levels of collagen type I and CTGF proteins using ELISA, and the expression levels of nuclear SMAD2/3/4, cytoplasmic SMAD2/3, and cytoplasmic SMAD4 proteins using the western blot technique.ResultsCompared to the control group, the injection of TAA resulted in a significant increase in serum levels of urea and creatinine, gene expression levels of TβRI and TβRII, protein expression levels of both collagen I and CTGF proteins, cytoplasmic SMAD2/3 complex, and nuclear SMAD2/3/4 (p-value < 0.0001), with significantly decreased levels of the co-SMAD partner, SMAD4 (p-value < 0.0001). Those effects were reversed considerably in both treatment groups, with the superiority of the exosomal treatment regarding the SMAD proteins and the expression levels of the TβRI gene, collagen I, and CTGF proteins returning to near-control values (p-value > 0.05).ConclusionUsing in vitro and in vivo experimental approaches, the research discovered a reno-protective role of silymarin and exosomes of BM-MSCs after thioacetamide-induced renal fibrosis in rats, with the advantage of exosomes.

Pharmacokinetics and Nephrotoxicity of Polymyxin MRX-8 in Rats: A Novel Agent against Resistant Gram-Negative Bacteria.

MRX-8 is a novel polymyxin for carbapenem-resistant Gram-negative infections that has been recently evaluated in Phase I clinical trials. Herein, its pharmacokinetics (PK) and nephrotoxicity in rats are reported for the first time. This study aimed at pre-clinical PK and safety assessments. An LC-MS/MS method was developed to determine concentrations of MRX-8 and its major deacylation metabolite, MRX-8039, in rat plasma. Animals were administered a single dose of MRX-8 (2, 4, 6, and 8 mg/kg) or comparator polymyxin B (PMB) (4 and 8 mg/kg) to compare the kidney injury known for the polymyxin drug class. Nephrotoxicity was evaluated using serum creatinine, blood urea nitrogen (BUN) biomarkers, and renal histopathology. In rats, MRX-8 displayed linear PK within the range of 2-8 mg/kg, with approximately 4% of MRX-8 converted to MRX-8039. MRX-8 induced only mild increases in serum creatinine and BUN levels, with an apparent decrease in nephrotoxicity within 24 h, in contrast to PMB, which exhibited a significant and more persistent toxicity. Additional nephrotoxicity biomarkers (plasma NGAL and urinary NGAL, KIM-1, and TIMP-1) have confirmed attenuated MRX-8 kidney injury. Histopathology has revealed significantly greater cellular/tissue toxicity for PMB as compared to MRX-8 (variances of p = 0.008 and p = 0.048 vs. saline control, respectively). Thus, MRX-8 induces a mild and reversible kidney injury in rats compared to PMB. These data support a continued evaluation of the novel polymyxin in human trials.

Lupus Nephritis Outcomes after Stopping Immunosuppression.

Background/Objectives: Immunosuppression (IS) is a standard therapy for lupus nephritis (LN). Data on the outcomes of patients with LN after the discontinuation of immunosuppression remain uncertain. This study aimed to evaluate the outcomes and results of patients with lupus nephritis (LN) who ceased immunosuppressive (IS) therapy. Methods: Records were obtained on the clinical and laboratory features of LN patients who were treated at our Lupus Unit. They included median values and ranges for various numerical variables such as patient age, disease duration, and treatment duration. Categorical variables such as gender, LN class, IS treatment type, and patient outcomes, which were categorized as either "stable" or "flare experienced", were presented as percentages and frequencies. A flare in LN was characterized by a two-fold increase in serum creatinine levels and a rise in proteinuria following the cessation of IS medication. Results: Outcomes were assessed for 45 patients with LN who ceased IS therapy after achieving remission. The patients' median age was 55 years (29-78). The median duration of treatment was 4 years (0.5-14). The LN histology distribution was class V = 24.4%, class IV = 17.8 %, class III = 17.8%, class III + IV = 15.6%, class III + V = 6.7%, class IV + V = 2.2%, and class II + IV and II = 2.2%. At the discontinuation of IS treatment, creatinine levels were elevated in 9/45 (20%) patients. Furthermore, 28.9% of patients relapsed after IS treatment discontinuation. Patients with anti-Smith antibodies (anti-Sm) were observed to have a higher occurrence of relapses, with six patients experiencing flare compared to four patients who remained stable (p = 0.03). Five (38.5%) of the patients with flares had high creatinine levels after IS discontinuation. Conclusions: Most of our patients maintained clinical remission and stable levels of LN parameters after IS treatment discontinuation. Those with a high serum creatinine level, ongoing proteinuria, depleted complement levels, and the presence of anti-Sm antibodies were more likely to experience flares after the discontinuation of IS therapy.

The Impact of Prenatal Alcohol Exposure on the Autonomic Nervous System and Cardiovascular System in Rats in a Sex-Specific Manner.

Fetal Alcohol Spectrum Disorder (FASD) is a consequence of prenatal alcohol exposure (PAE) associated with a range of effects, including dysmorphic features, prenatal and/or postnatal growth problems, and neurodevelopmental difficulties. Despite advances in treatment methods, there are still gaps in knowledge that highlight the need for further research. The study investigates the effect of PAE on the autonomic system, including sex differences that may aid in early FASD diagnosis, which is essential for effective interventions. During gestational days 5 to 20, five pregnant female Wistar rats were orally administered either glucose or ethanol. After 22 days, 26 offspring were born and kept with their mothers for 21 days before being isolated. Electrocardiographic recordings were taken on the 29th and 64th day. Heart rate variability (HRV) parameters were collected, including heart rate (HR), standard deviation (SD), standard deviation of normal-to-normal intervals (SDNN), and the root mean square of successive differences between normal heartbeats (RMSSD). Additionally, a biochemical analysis of basic serum parameters was performed on day 68 of the study. The study found that PAE had a significant impact on HRV. While electrolyte homeostasis remained mostly unaffected, sex differences were observed across various parameters in both control and PAE groups, highlighting the sex-specific effects of PAE. Specifically, the PAE group had lower mean heart rates, particularly among females, and higher SDNN and RMSSD values. Additionally, there was a shift towards parasympathetic activity and a reduction in heart rate entropy in the PAE group. Biochemical changes induced by PAE were also observed, including elevated levels of alanine transaminase (ALT) and aspartate aminotransferase (AST), especially in males, increased creatinine concentration in females, and alterations in lipid metabolism. PAE negatively affects the development of the autonomic nervous system, resulting in decreased heart rate and altered sympathetic activity. PAE also induces cardiovascular abnormalities with sex-specific effects, highlighting a relationship between PAE consequences and sex. Elevated liver enzymes in the PAE group may indicate direct toxic effects, while increased creatinine levels, particularly in females, may suggest an influence on nephrogenesis and vascular function. The reduced potassium content may be linked to hypothalamus-pituitary-adrenal axis overactivity.

A Retrospective Study Comparing Pharmacomechanical Thrombectomy with Catheter-Directed Thrombolysis for Acute Deep Venous Thrombosis

PurposeThis study aims to conduct a comparative analysis of the clinical efficacy and safety between pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) in the context of acute lower-extremity deep venous thrombosis (LEDVT). Materials and MethodsA retrospective review of our institution's patient database spanning from February 2011 to December 2019 was performed to identify cases of acute LEDVT. The patients were categorized into two distinct groups based on the thrombolytic interventions administered: the PMT group, specifically denoting PMT with AngioJet in our investigation, and the CDT group. Comprehensive data sets encompassing patient demographics, risk factors, procedural specifics, thrombolysis grading, and complications were collected. Subsequent follow-up evaluations at the two-year mark post-treatment included assessments of post-thrombotic syndrome (PTS) and the quality of life (QOL). ResultsAmong the 348 patients identified (mean age: 50.12 ± 15.87 years; 194 females), 200 underwent catheter-directed thrombolysis (CDT) during the early stage (2011 to 2017), while 148 received pharmacomechanical thrombectomy (PMT) between 2017 and 2019. Baseline data between the two groups exhibited no statistically significant differences. Thrombus scores significantly decreased in both cohorts post-therapy (each p < 0.001).Patients subjected to PMT demonstrated higher thrombolysis rates (77.35±9.44% vs 50.85±6.72%), reduced administration of the thrombolytic agent urokinase [20(20-20) vs 350(263-416), p < 0.001], larger limb circumference differences (above the knee: 6.03±1.76cm vs 4.51±1.82cm, p < 0.001; below the knee: 2.90±1.16cm vs 2.51±0.90cm, p < 0.001), and shorter lengths of stay (7.19±3.11 days vs 12.33±4.77 days, p < 0.001). However, the PMT group exhibited a higher decline in hemoglobin levels (13.41±10.59 g/L vs 10.88±11.41 g/L, p = 0.038) and an increase in creatinine levels [9.58(2.32-15.82) umol/L vs 4.53(2.87-6.08) umol/L, p < 0.001] compared to the CDT group. No statistically significant differences were observed in the numbers of balloon angioplasty, stent implantation (each p > 0.050), and minor and major complications between the two groups. At the 1-year follow-up, post-thrombotic syndrome (PTS) occurred in 13.51% of the PMT group compared to 26% of the CDT group (p = 0.025), with a higher incidence of moderate-severe PTS in the CDT group (8% vs 2.7%, p = 0.036). At the 2-year follow-up, PTS was observed in 16.2% of the PMT group and 31.5% in the CDT group, p = 0.004. Preoperative and postoperative D-values of SF-36 PCS and SF-36 MCS showed no statistically significant between-group differences. ConclusionIn our institutional experience, both pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) have proven to be effective and safe therapeutic approaches for managing acute lower-extremity deep venous thrombosis (LEDVT). PMT, in particular, demonstrated superior efficacy in achieving thrombosis resolution and mitigating the risk of post-thrombotic syndrome, affirming its role as a favorable intervention in this clinical context.

The Incidence of Abnormal Preoperative Testing Among Elective Surgery Patients in a Referral Hospital in Southern Saudi Arabia.

Background Preoperative investigations are important to assess the clinical condition of patients who undergo elective surgical procedures. However, there is still debate about the usefulness of performing preoperative investigations. We aimed to determine the prevalence of routine preoperative investigation abnormalities among elective general surgery patients. Methodology This retrospective hospital-record-based study was conducted at the King Abdullah Hospital in Bisha Province, southern Saudi Arabia. General and clinical data of 968 patients who underwent elective surgical interventions from February 2022 to January 2023 were retrieved and analyzed. Result A total of 968 patients (578 females and 390 males) aged between 14 and 80 years were included in the study. Four hundred and eleven (42.5%) patients were in the age groupof 40 years and above. The commonly detected comorbidities among the patients were diabetes (15%), hypertension (12%), respiratory diseases (7.5%), and cardiac diseases (2.5%). Abnormalities related to hemoglobin (31%), total leucocyte count (12.7%), and platelets (8.5%) were found in 968 patients. Around 15% of patients had increased creatinine levels. Hypokalemia was observed in 6.8% of patients. Increased liver enzymes were reported in limited proportions (10% to 14%) of patients. Slightly abnormal radiological findings were reported for chest X-ray (CXR) (2.8%), electrocardiogram (ECG) (2%), and Doppler echocardiography (Echo) (0.8%). A statistically significant association between the age of the patient and abnormal findings of ECG (p <.001), Echo (p = .001), and CXR (p <.001). Cardiac abnormalities were commonly associated with patients of ≥ 40 years. Abnormal cardiac findings (CXR, ECG, Echo) were significantly (p<.05) increased with the presence of diabetes, hypertension, and cardiovascular comorbidities. Conclusions Preoperative testing revealed limited proportions of abnormal findings among patients with elective surgical procedures. Routine ordering of many preoperative investigations without specifications may not predict postoperative complications of the patients. Therefore, undertaking preoperative testing should be guided by targeted history, physical examination, clinical risk factors, and type of surgical procedure intended to be performed.

Impact of Amphetamine and Captagon abuse on the liver and renal function

Background. Addiction is a multifaceted brain disorder characterized by compulsive substance use despite harmful consequences. The physiological effects of drugs, such as amphetamines and captagon, on organ functions remain a significant concern, with varying impacts based on substance type and duration of use. Aim of study. This study aimed to investigate the impact of amphetamine and captagon abuse on liver and kidney functions. By comparing physiological parameters between individuals with substance abuse history and a control group, the study sought to elucidate the health implications of long-term drug use. Methods. The study involved 50 participants: 30 with a history of substance abuse and 20 healthy controls. It assessed liver and kidney functions using biochemical and ELISA tests to measure AST, ALT, ALP, Total Serum Bilirubin, Serum Albumin, Serum Creatinine, and Blood Urea. Results. The study revealed a significant difference between drug users and controls, with drug users exhibiting higher levels of urea and serum creatinine. Liver function tests showed increased GOT, GPT and ALP levels in drug users. Furthermore, total serum bilirubin was significantly higher in drug users, indi­cating liver impairment. Age-related analysis showed more severe renal and liver dysfunction in older drug users, with notable increases in urea and serum creatinine levels with age (p=0.001 and p=0.009, respectively). Conclusion. Both amphetamines and captagon pose a significant health risk to renal and liver functions. This underscores the need for awareness and interventions targeted at mitigating the health implications of substance abuse, highlighting the importance of continuous monitoring and treatment strategies for affected individuals.