Kidney Function Parameters Research Articles

Jian-Pi-Yi-Shen formula ameliorates renal fibrosis-induced anemia in rats with chronic kidney disease

Ethnopharmacological relevanceJian-Pi-Yi-Shen (JPYS) formula is an effective herbal therapy against renal injury, and JPYS has been clinically applied to ameliorate chronic kidney disease (CKD) and CKD-associated anemia. Increasing evidence supports the link between renal fibrosis and anemia in CKD. JPYS possessed anti-fibrosis effects in experimental CKD. Nevertheless, research on the mechanisms of JPYS in ameliorating renal anemia (RA) through suppressing renal fibrosis remains to be clarified. Aim of the studyOur study here was carried out to investigate the mechanisms of JPYS in protecting against RA. Materials and methodsAn adenine-induced anemia model in rats with CKD at three different time points was established, and bio-samples taken from each group were analyzed. Biochemical analysis was employed to detect kidney function and hematological parameters. Masson staining was used to evaluate renal fibrosis of rats. Western blot and immunohistochemistry were utilized to evaluate the expressions of fibrotic markers, erythropoietin (EPO) and hypoxia inducible factor-2α (HIF-2α) in the kidneys of rats. Subsequently, transcriptomic analysis was conducted to disclose the possible mechanisms of JPYS in treating RA. Finally, the expression levels of key targets were analyzed and validated by using Western blot and enzyme-linked immunosorbent assay (ELISA). ResultsJPYS treatment improved kidney function, suppressed renal fibrosis and enhanced hematological parameters in CKD rats. Moreover, JPYS treatment restored the increased expression levels of fibrotic markers and the declined EPO with time dependence. In parallel, data indicated JPYS treatment stimulated the translocation of HIF-2α into nucleus in the renal interstitium and thus promoted the expression of EPO. Transcriptomic profiling disclosed that activations of both nuclear factor kappa B (NF-κB) and transforming growth factor-β (TGF-β)/Smad pathways were closely associated with RA. Ultimately, experimental validation results presented that the increased expressions of target proteins from the above-mentioned two pathways in the kidneys were decreased significantly after JPYS treatment. ConclusionOur findings suggest that JPYS may improve RA by alleviating renal fibrosis, and the mechanisms of which involve in inhibiting the NF-κB and TGF-β/Smad pathways.

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

Ocimum basilicum and Lagenaria siceraria Loaded Lignin Nanoparticles as Versatile Antioxidant, Immune Modulatory, Anti-Efflux, and Antimicrobial Agents for Combating Multidrug-Resistant Bacteria and Fungi.

Lignin nanoparticles emerged as a promising alternative for drug delivery systems owing to their biodegradability and bioactive properties. This study investigated the antimicrobial activity of the ethanolic extract of Ocimum basilicum-loaded lignin nanoparticles (OB-LNPs) and Lagenaria siceraria seed oil-loaded lignin nanoparticles (LS-LNPs) to find a solution for antimicrobial resistance. OB-LNPs and LS-LNPs were tested for their antimicrobial potential against Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica, Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum canis. OB-LNPs and LS-LNPs were further tested for their anti-efflux activity against ciprofloxacin-resistant Salmonella enterica strains and for treating Salmonella infection in a rat model. We also investigated the antifungal efficacy of OB-LNPs and LS-LNPs for treating T. rubrum infection in a guinea pig model. Both OB-LNPs and LS-LNPs showed strong antimicrobial potential against S. Typhimurium and T. rubrum infections. LS-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-4 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.125-1 µg/mL. OB-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-2 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.25-2 µg/mL. OB-LNPs and LS-LNPs downregulated the expression of ramA and acrB efflux pump genes (fold change values ranged from 0.2989 to 0.5434; 0.4601 to 0.4730 for ramA and 0.3842-0.6199; 0.5035-0.8351 for acrB). Oral administration of OB-LNPs and LS-LNPs in combination with ciprofloxacin had a significant effect on all blood parameters, as well as on liver and kidney function parameters. Oxidative stress mediators, total antioxidant capacity, and malondialdehyde were abolished by oral administration of OB-LNPs and LS-LNPs (0.5 mL/rat once daily for 5 days). Interferon-γ and tumor necrosis factor-α were also reduced in comparison with the positive control group and the ciprofloxacin-treated group. Histopathological examination of the liver and intestine of OB-LNPs and LS-LNPs-treated rats revealed an elevation in Salmonella clearance. Treatment of T. rubrum-infected guinea pigs with OB-LNPs and LS-LNPs topically in combination with itraconazole resulted in a reduction in lesion scores, microscopy, and culture results. In conclusion, OB-LNPs and LS-LNPs possess immunomodulatory and antioxidant potential and can be used as naturally derived nanoparticles for drug delivery and treatment of Salmonellosis and dermatophytosis infections.

Ganoderma pfeifferi Bres. and Ganoderma resinaceum Boud. as Potential Therapeutic Agents: A Comparative Study on Antiproliferative and Lipid-Lowering Properties.

Medicinal mushrooms, especially Ganoderma species, hold immense promise for the production of a wide range of bioactive compounds with various effects. The biochemical potential of indigenous fungal strains, specific to a region, could play a critical role in the continuous search for novel strains with superior activities on a global scale. This research focused on the ethanolic (EtOH) and hot-water (H2O) extracts of fruiting bodies of two wild-growing Ganoderma species: G. pfeifferi and G. resinaceum, with the aim of assessing their nutritional (total carbohydrate content-TCC) and mineral composition in relation to bioactive properties: antioxidant, antiproliferative and lipid-lowering. Atomic absorption spectrophotometry (AAS) revealed that G. pfeifferi is a promising source of minerals that are essential for numerous physiological functions in the human body like bone health and muscle and nerve function, with Ca (4.55 ± 0.41 mg/g d.w.) and Mg (1.33 ± 0.09 mg/g d.w.) being the most abundant macroelement present. Zn, Mn, and Cr were particularly notable, with concentrations ranging from 21.49 to 41.70 mg/kg d.w. The EtOH extract of G. pfeifferi demonstrated significantly elevated levels of TCC, essential macromolecules for energy and structural functions in the body, with higher quantities of all three standard carbohydrates detected in this type of extract. Similar to the revealed composition, the same species, G. pfeifferi, stood out as the most prominent antioxidant agent, with the H2O extract being stronger than EtOH in the ABTS assay (86.85 ± 0.67 mg TE/g d.w.), while the EtOH extract displayed the highest anti-OH• scavenging ability (IC50 = 0.18 ± 0.05 μg/mL) as well as the most notable reducing potential among all. The highest antiproliferative effect against the breast cancer cell line (MCF-7), were demonstrated by the H2O extracts from G. resinaceum with the most pronounced activity after 24 h (IC50 = 4.88 ± 0.50 μg/mL), which surpasses that of the standard compound, ellagic acid (IC50 = 33.94 ± 3.69 μg/mL). Administration of both Ganoderma extracts mitigated diabetic lipid disturbances and exhibited potential renal and hepatic protection in vivo on white Wistar rats by the preservation of kidney function parameters in G. resinaceum H2O pre-treatment (urea: 6.27 ± 0.64 mmol/L, creatinine: 50.00 ± 6.45 mmol/L) and the reduction in ALT levels (17.83 ± 3.25 U/L) compared to diabetic control groups treated with saline (urea: 46.98 ± 6.01 mmol/L, creatinine: 289.25 ± 73.87 mmol/L, and ALT: 60.17 ± 9.64 U/L). These results suggest that pre-treatment with G. resinaceum H2O extracts may have potential antidiabetic properties. In summary, detected microelements are vital for maintaining overall health, supporting metabolic processes, and protecting against various chronic diseases. Further research and dietary assessments could help determine the full potential and applications of the two underexplored Ganoderma species native to Serbia in nutrition and health supplements.

Analysis of factors predisposing to increased number of complications and mortality in patients with Fournier’s gangrene

Introduction and objective: Fournier’s gangrene is an infectious disease affecting the soft tissues of the groin area. The primary cause is bacterial infection of the tissues, which can quickly lead to necrosis and even systemic infection. Analysing the risk factors allows for estimating the potential course and complications of the disease. Materials and methods: An analysis was conducted on a group of 53 patients with Fournier’s gangrene hospitalised between 2010 and 2022 in the Military Institute of Medicine – National Research Institute, to assess the most common risk factors with a view to determining if their occurrence affects the length of hospitalisation, the severity of the disease, inflammatory parameters, kidney function, and mortality. Results: Diabetes, infection with resistant bacteria, and previous urological procedures did not significantly affect any of the examined parameters. Cardiovascular diseases, poor social status, and other cancers significantly increased the severity of the disease determined by the Fournier’s Gangrene Severity Index (FGSI). Cardiovascular diseases significantly worsened kidney function parameters. Cardiovascular and gastrointestinal diseases were the only ones significantly increasing mortality in the studied group. Hospitalisation during the COVID-19 pandemic only led to a significant increase in inflammatory parameters. No correlation was found between the number of risk factors and the length of hospitalisation, while a positive correlation was shown between the risk factors and the FGSI score. Conclusions: Patients diagnosed with Fournier’s gangrene and having cardiovascular or gastrointestinal diseases should undergo closer clinical observation to reduce mortality and the risk of complications. Patients with a higher number of risk factors present a more severe course of infection, as assessed by the FGSI.

Toxicological Effects of Colloidal Silver Nanoparticles on Rat Health: Assessing Physiological, Hematological, Biochemical, and Behavioral Parameters

Introduction: Nanotechnology, a rapidly evolving field, has introduced silver nanoparticles (AgNPs) as promising materials with diverse applications. Their unique properties have revolutionized industries, raising concerns about potential health implications. This study aims to comprehensively evaluate the toxicological effects of AgNPs on rat health through a multidimensional approach, encompassing physiological, hematological, biochemical, and behavioral assessments. Methodology: Colloidal AgNPs with a minimum purity of 99.98% were synthesized using an inductive coupled plasma (ICP) method. Sixty male specific-pathogen-free (SPF) Wistar rats were exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs, alongside a control group. Throughout the exposure period, comprehensive assessments, including body weight changes, food intake, water consumption, hematological and biochemical parameters, and behavioral evaluations, were systematically conducted. The statistical analysis employed a combination of one-way ANOVA and Kruskal-Wallis tests for robust data interpretation. Results: Rats exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs displayed no significant changes in food intake, water consumption, or blood parameters compared to the control group. However, a notable reduction in body weight was observed in the high-dose group, suggesting a potential dose-dependent impact. Biochemical analyses indicated no significant differences in liver and kidney function parameters for the low-dose group, but the high-dose group exhibited potential elevation in liver enzymes, necessitating further scrutiny. Behavioral assessments revealed no significant alterations in open-field behavior or cognitive function, indicating minimal impact on exploratory and cognitive abilities within the tested doses. Conclusion: AgNPs demonstrated minimal impact on certain parameters, the high-dose group exhibited notable body weight reduction and potential liver enzyme alterations, warranting further investigation. Behavioral assessments indicated no significant cognitive effects. These findings emphasize the importance of continued research for informed regulatory decisions and the safe utilization of AgNPs in consumer products.

Analysis of physical traits, clinical parameters, and energy metabolism of invivo- and invitro-derived Flemish newborn calves during the first day of life.

Studies investigating physiological deviations from normality in newborn calves derived from invitro fertilization procedures remain important for the understanding of factors that reduce calf survival after birth. The aim of this study was to investigate parameters affecting health and welfare of newborn Flemish calves derived from invitro embryo production (IVP) in the first hours of life in comparison to invivo-derived calves. Physical traits of newborn calves and fetal membranes (FM) were recorded soon after birth. Newborn venous blood samples were collected at several time points within the first 24 h of life for analyses of energy substrates, electrolytes, blood gases, acid-base balance, blood chemistry, and haematology. A liver biopsy was taken within the first hour after birth for analysis of gene expression of key enzymes of the fructolytic and glycolytic pathways. Newborn IVP calves were heavier and larger at birth, which was associated with heavier FM. At several time points during the first 24 h of life, IVP-derived calves had altered rectal temperature, blood gases, electrolyte concentrations, blood parameters for liver, kidney and muscle function, and acid-base balance, plasma lipid metabolism, and hemogram parameters. The relative mRNA abundances for triokinase and lactate dehydrogenase-B were greater in IVP calves. In summary, IVP-derived newborn calves were at higher risk of clinical problems after birth, which was markedly greater in heavier and larger calves. Such animals take longer to adapt to extrauterine life and should receive a special attention during the immediate neonatal period.

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events.

Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage. Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg). The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK's ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1β and TNF-α, besides downregulation of NF-κB and IL-1β expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features. These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.

A hormonal side effect of anabolic steroids among a sample of Baghdad male bodybuilders

Anabolic-androgenic steroids (AAS) are used widely, but in illegal ways mostly by young men as performance-enhancing and image-enhancing drugs (IPED). long-term usage of AAS, usually in conjunction with other illegal substances, can have extremely detrimental impacts on the reproductive system. The primary goal of this study was to examine any possible detrimental effects of AAS on sex hormone levels, a liver and kidney function in individuals who frequent fitness centers in Iraq-Baghdad. In this research, there are 60 participants (20–37 years old); 30 athletes who visited the different gyms in Baghdad/ Iraq and used AAS such as testosterone, Boldenone, Cybontae, Deca Durabellin; and 30 athletes who did not take any synthetics hormones and serve as control. All participants answered the questionnaire form which included their age, the type of used AAS, when they started to take it, and the total usage number per week. The blood (5 ml) was drawn from every participant to separate the serum. The serum was used to measure some hormones (Testosterone, FSH, LH, prolactin and Estrodiol) and liver and kidney function parameters. The results showed a significantly lower level of testosterone and FSH in the AAS-users’ bodybuilding group compared to the control group. In comparison with the control group, there was a notable rise in the PRL level in the serum of AA users. However, when comparing the serum levels of LH and Estrodiol in the AAS-user group to those in the control group, no discernible variations were seen. AAS users had a significantly higher level of ALT and lower ALP than controls, although there is no difference in AST levels between the two groups. The creatine level was significantly higher in the AAS-user compared to the control group, but not urea. In conclusion, the effects of AAS and other supplements on sex hormones and kidney, liver function, and vary depending on how long they are used, with the effects of AAS being more pronounced. Therefore, there is a need for culturally sensitive measures to prevent steroid abuse among youth.

Microplastics exposure altered hematological and lipid profiles as well as liver and kidney function parameters in albino rats (Rattus norvegicus).

The global occurrence of microplastics and their poorly understood health implications underscore the need for scientific investigation. This study aimed to assess the effects of microplastics exposure. Twenty-five (25) albino rats (Rattus norvegicus) were divided into five (5) groups, each consisting of five rats. Group 1 (the negative control) received normal feed; group 2 (the positive control) was administered a 10 % lead acetate solution; and groups 3, 4, and 5 were administered 1 %, 5 %, and 10 % microplastic solutions, respectively. The rats were monitored for 28 days, after which blood samples were taken for hematological and lipid profiles as well as liver and kidney function parameters. The results revealed dose-dependent significant (p < 0.05) alterations in the health indices of the treated rats and the positive control compared with the negative control. Specifically, the hematological parameters, including the white blood cells (WBC) and its subtypes, were reduced, indicating immunosuppressive effects, and the red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), platelets, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were reduced, indicating anemia. The 1 % and 5 % microplastic solutions raised the lipid profiles of the treated rats, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), while the 10 % concentration decreased them, causing hyperlipidemia and hypolipidemia, respectively. The liver function parameters, including total protein (TP), albumin (ALB), aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), were elevated, indicating liver damage. Elevation of kidney function parameters, including sodium ion (Na+), potassium ion (K+), chloride ion (Cl-), urea, and creatinine (CRT), were noticed, suggesting kidney injuries. It can be inferred from these results that microplastics are toxic. Hence, human exposure to microplastics should be reduced to a minimum.

Cardioactive and Antihypertensive Properties of Tinospora crispa: An In vivo Approach

Tinospora crispa, a potent medicinal plant with multiple clinical indications, has a recorded history of ethnopharmaceutical use as an antihypertensive and has also been reported for its cardioactive properties. The antihypertensive and cardioactive properties of the plant were investigated in two different animal models of hypertension (ethanol-induced and digoxin-induced). In both models, the plant’s ethanolic extract was observed to exert a dose-dependent effect. Furthermore, treatment with the ethanolic extract resulted in no undesirable changes in liver and kidney function parameters such as serum SGOT, SGPT and creatinine levels. The ethanolic extract of the plant may, therefore, be considered safe and effective for the treatment of hypertension, although further extensive research into this is warranted. Dhaka Univ. J. Pharm. Sci. 23(1): 1-6, 2024 (June)

Protective Effects of Aqueous Extract of Piper nigrumWhole Fruits Against Tramadol-induced Hepato-and Nephrotoxicity in Wistar Rats

Tramadol, a widely used analgesic, is becoming more abused in most countries. Hence, this study aims to investigate the protective effects of aqueous extract of Piper nigrum whole fruits on tramadol-induced toxicity in male Wistar rats. Six groups (A-F) of male Wistar rats were exposed to a 14-day oral treatment. Specifically, the control group, induced group (tramadol at 60 mg/kg), reference drug group (Vitamin C at 250 mg/kg) and the extract groups (250, 500, and 1000 mg/kg). The levels of liver cellular markers ALT, AST and ALP as well as the kidney function parameters (urea, creatinine and uric acid) showed a significant(p&lt;0.05) increase following the administration of 60 mg/kg of tramadol and a significant reversal was observedfollowing the administration of extract in a dose dependent manner. However, K+and HCO3-showed a significant(p&lt;0.05) decrease and were also reversed following the administration of extract in a dose dependent manner. Tramadol also showed a significant(p&lt;0.05) increase inthe concentration of WBC and LYM, and a significant(p&lt; 0.05) decrease inthe levels of RBC, HGB, HCT, RDW-SD, RDW-CV, and MPV. The reference drug and the extract showed significant (p&lt; 0.05) reversal inthe levels of these biochemical parameters. Histological examination revealed normal liver and kidneyarchitecture in all groups, indicating no signs of inflammation or damage. These findings revealed that the aqueousextracts from whole fruits of P. nigrum at concentrations of 250 and 500 and 1000 mg/kg may potentially offer protection and general improvement in the overall health status and function of the hematopoietic system.

Long-Term Renal Function with Cardiac Contractility Modulation Therapy

Introduction: Cardiac implantable electrical devices are able to affect kidney function through hemodynamic improvements. The cardiac contractility modulation (CCM) is a device-based therapy option for patients with symptomatic chronic heart failure (HF) despite optimized medical treatment. The long-term cardiorenal interactions for CCM treated patients are yet to be described. Methods: CCM recipients (n = 187) from the Mannheim Cardiac Contractility Modulation Observational Study (MAINTAINED) were evaluated in the long-term (up to 60 months) for changes in serum creatinine, estimated glomerular filtration rate (eGFR), other surrogate markers of kidney function, and the chronic kidney disease (CKD) stage distribution. With regard to kidney function at baseline, the patients were furthermore grouped to either advanced CKD (aCKD, CKD stage ≥3, eGFR≤59 mL/min/1.73 m2, n = 107) or preserved kidney function and mild CKD (pCKD, CKD stages 1–2, eGFR≥60 mL/min/1.73 m2, n = 80). The groups were compared for differences regarding kidney function, New York Heart Association classification (NYHA), biventricular systolic function, HF hospitalizations and other parameters in the long-term (60 months). Results: CKD stage distribution remained stable during the entire follow-up (p = 0.65). An increase in serum creatinine (1.47 ± 1 vs. 1.6±1 mg/dL) with a corresponding decline of eGFR (58.2 ± 23.4 vs. 54.2 ± 24.4 mL/min/1.73 m2, both p < 0.05) were seen after 60 months but not before for the total cohort, which was only significant in pCKD patients in terms of group comparison. Mean survival (54.3 ± 1.3 vs. 55.3 ± 1.2 months, p = 0.53) was comparable in both groups. Improvements in NYHA (3.11 ± 0.46 vs. 2.94 ± 0.41–2.28 ± 0.8 vs. 1.94 ± 0.6) and LVEF (24.8 ± 7.1 vs. 22.9 ± 6.6–31.1 ± 11.4 vs. 35.5 ± 11.1%) were likewise similar after 60 months (both p < 0.05). The aCKD patients suffered from more HF hospitalizations and ventricular tachycardias during the entire follow-up period (both p < 0.05). Conclusions: The kidney function parameters and CKD stage distribution might remain stable in CCM treated HF patients in the long-term, who experience improvements in LVEF and functional status, regardless of their kidney function before. An impaired kidney function might be associated with further cardiovascular comorbidities and more advanced HF before CCM, and could be an additional risk factor of HF complications afterward.

Evaluation of Serum Biochemical Parameters in Male Wistar Rats Administered with Azadirachta Indica Silver Nanoparticles

The excessive exposure to silver nanoparticles (AgNPs) has raised concerns about their possible risks to the human health. This study investigated the effects of administering silver nanoparticles on serum biochemical parameters in male wistar rats. Synthesis of AgNPs from AgNO3 and plant extract was achieved using standard methods. At the same time, the characteristic peak of the synthesized AgNPs was determined using a UV-VIS spectrophotometer at a resolution of 1 nM. The crystal structure of AgNPs was determined using the Fourier Transform Infrared Spectroscopy (FTIR), while kidney and liver function parameters were carried out using serum with the aid of biochemical kits. A total of sixteen male wistar rats were randomly allotted into four experimental groups of four rats per group. Group 1 served as the control and received potable water. Groups two, three and four were orally administered with varying concentrations of silver nanoparticles (AgNPs) at 100, 250 and 500 mg/kg daily for two weeks respectively. Following cessation of treatments, rats were sacrificed under anaesthetization, and serum samples were collected for analysis. The result revealed that the absorption characteristic peak of the ultraviolet-visible spectrum of the silver nanoparticles synthesized was 450 nM. It was also observed that the urea, creatinine, and potassium ion (K+) had no significant difference (P&gt;0.05). However, the values of total bilirubin (11.00±3.68 mg/dl) and Sodium ion (140.00±3.54) in group 4 decreased significantly (P&lt;0.05) when compared to group 2, 3 and the control group. Also, it was observed that there is a significant increase (P&lt;0.05) in the value of Chloride ion in all the administered group when compared to the control. Synthesized silver nanoparticles from A. indica also affected the level of liver parameters such as ALT, ALP, TP AST, and Albumin in a non-significant way. This study found no evidence of hazardous effects from silver nanoparticles, which could be attributed to the minimal dosage of AgNPs or the nanoparticles' source.

Is resveratrol really effective in kidney disease?: A different perspective than ever before

Background Chronic kidney disease (CKD) is a global health problem and it is stated that the use of resveratrol supplement contributes to the protection of kidney health. In this study, it was aimed to evaluate the effect of resveratrol supplementation on kidney function, inflammation and histopathological findings in rats with experimental adenine-induced kidney damage. Methods Three different groups of 10 randomly selected rats were formed. The first group was the negative control group, the second group was the uremic control group (KDG), and the third group was the group in which uremia was created and resveratrol was applied (RG). Kidney damage was induced by administration of 200 mg/kg adenine. Resveratrol supplementation was administered at 20 mg/kg after kidney damage. Serum urea, creatinine, indoxyl sulfate (IS), p-cresol, glomerular filtration rate, C-reactive protein (CRP); interleukin (IL)-6 and tumor necrosis factor (TNF)-α gene expression levels and histopathological findings were evaluated. Results It was determined that resveratrol supplement applied after the formation of connective tissue in renal failure didn’t have an improvement effect on the urine amount, kidney function and inflammatory parameters and histopathological changes (p > 0.05). Just, the increase in the CRP value of KDG (p < 0.05) was not observed in RG. Conclusion The findings suggest that resveratrol administered after kidney damage with adenine has no effect on kidney disease.

#2120 Impact on CKD classification and comorbidities using GFR estimated by European Kidney Function Consortium equation in kidney transplant recipients

Abstract Background and Aims In 2020, European Kidney Function Consortium (EKFC) proposed a new equation that estimates glomerular filtration rate (GFR) in European population. Few studies have compared EKFC with CKDEPI, particularly in kidney transplant (KT) recipients. Chronic Kidney Disease (CKD) classification by KDIGO is used not only by nephrologists who evaluate more parameters of kidney function, but also by every other specialist who are going to be guided mainly by this stage. Our objective is to compare EKFC equation and CKDEPI in classifying CKD in KT patients and its relationship with associated comorbidities. Method We conduct a retrospective observational study including all KT performed at our centre from 1993 to 2022 with survival greater than one year. We collect creatinine, haemoglobin (Hb), phosphorus (P−), potassium (K+), and bicarbonate (Bic) values at three months and one-year post-transplant. We define anaemia as Hb &amp;lt; 11 g/dl, hyperphosphataemia as serum P− &amp;gt; 4.5 mg/dl, hyperkalaemia as serum K+ &amp;gt; 5 mEq/ml, and acidosis as Bic &amp;lt; 22 mEq/L. We calculate estimated GFR (eGFR) using CKDEPI and EKFC equations, classify CKD stage according to KDIGO, and compare both results in terms of correlation and differences. We use Kappa Coefficient and Chi-Square by contingency tables, and ROC curves with homogeneity test for prediction of these comorbidities. We use SPSS and MedCalc as statistics programs. Results We include 968 KT, with median age at the time of transplant 52.75 year [41.25-61.27]. 294 KT (30.4%) are in women. Comorbidity frequencies are depicted in Table 1. ROC analysis shows no significant differences in predicting acidosis at one year, hyperphosphataemia at any time, hyperkalaemia at 3rd month, anaemia at any time, and composite event at any time. We find significant differences in favour to CKDEPI for acidosis at 3rd month (ΔAUC 0.00575 95% CI [0.00182-0.00969]; p = 0.0042) and for hyperkalaemia at one year (ΔAUC = 0.00853 [0.00161-0.0154]; p = 0.0157). Through contingency tables we compare classification into stages, finding very good agreement based on the Kappa coefficient (κ) but significant differences by Chi-Square. With κ = 0.905, EKFC reclassifies 70 patients, 7.23% overall, but not significantly down nor upstaging (31 vs 39). It reclassifies more men than women: 8.46% vs 4.42%. In 10-year age groups, the largest reclassification occurs in the 70-80 years group, a 17.07% with κ = 0.774, all cases upstaged. At one-year eGFR, contingency tables also show a very good agreement based on κ but significant differences by Chi-Square. EKFC reclassifies 83 KT (κ = 0.887), 8.57% overall. It reclassifies 7.48% women and 9.05% men. In 10-year age groups, the largest reclassification occurs in 20-30 years group with 17.24% (κ = 0.767) and 14.81% in 70-80 years (κ = 0.796). All patients in these groups were upstaged. We resume graphically the reclassification of the groups in Fig. 1, observing how EKFC upstages CKD (worsen CKD stage) in high eGFR stages, and downstages CKD in low eGFR stages. Conclusion Estimation of GFR in KT recipients using the new EKFC equation yields similar results to CKDEPI, showing very good agreement for CKD classification although there is a non-negligible percentage of reclassification, which may be clinically relevant in terms of treatment indications and diagnostic tests. It is to a worse CKD stage in high eGFR and to a better stage in low eGFR, and when EKFC reclassification percentage is greater—in the extreme ages of our cohort—it is always by upstaging. Except for minimal differences which we consider clinically inconsequential, we find no significant differences between both equations in discriminating presence of hyperphosphatemia, hyperkalaemia, anaemia or acidosis.

#1493 Upregulated miR-205 as a biomarker of diet-induced obesity-related glomerulopathy

Abstract Background and Aims Obesity is a modifiable risk factor for the development and progression of chronic kidney disease (CKD). Pathways through which obesity might cause renal disease are not completely understood, as not all obese subjects develop CKD. In terms of deepening the knowledge of the preliminary steps of obesity-related renal damage, our group has developed a diet-induced obese murine model with obesity related glomerulopathy (ORG). The objective of this study was to investigate ORG at a cellular, structural and transcriptomic level as a way to discover the triggering pathogenic phenomena of ORG and evaluate potential biomarkers. Method Thirty Wistar rats were randomized into two groups: control rats (n = 15), which were fed with standard diet (SD) and study rats (n = 15), which were fed with high-fat diet (HFD). After 10 weeks, weight, parameters of kidney function, renal histological features, transcriptomic changes, miRNA and mRNA isolation were compared. Results HFD gained significantly more weight (55.8%) than SD(29.2%), p = 0.001. Albuminuria was also significantly higher in HFD (10,384.04) compared with SD (5,845.45), p = 0.001. HFD rats showed typical lesions of early-stages of ORG, with a predominance of mesangial matrix increase (MMI) and podocyte hypertrophy (PH). All histologic lesions correlated with genes differentially expressed (DE) in kidneys of HFD group and, both MMI and PH, also correlated with specific miRNAs DE in the urine of HFD group. The functional analysis showed 4 miRNAs DE in the kidneys of HFD group that negatively regulates PTEN gene, which promotes podocyte endocytosis of lipids in ORG. The electronic microscope confirmed the spaces of lipid vacuoles in the podocytes of HFD rats. Between those 4 miRNAs DE, miR-205 was also found to be upregulated in the urine of HFD group. Conclusion Wistar rats fed with HFD for 10 weeks developed early-stages of ORG, with a specific targetome of miRNAs and gene expression. The upregulation of miR-205 in kidney and its isolation in urine is associated with lipid endocytosis of podocytes, which takes place in the early-stages of ORG and could become a plausible biomarker of early-stages of ORG and open new avenues for future therapeutics research.

#2615 Altered peroxidasin expression pattern in IgA nephropathy

Abstract Background and Aims PXDN is a multifunctional heme peroxidase responsible for the crosslinking of type IV collagen protomers at basement membranes, playing a crucial role in the extracellular matrix dynamics. In renal pathophysiology, increased PXDN expression has been associated with pro-fibrotic and pro-carcinogenic mechanisms and we have shown that PXDN is expressed throughout all kidney compartments since the early stages of nephrogenesis. However, the role of PXDN in kidney health and disease remains largely unknown. In this work we performed a comparative analysis of PXDN expression between renal biopsy samples from IgA nephropathy (IgAN) patients and healthy kidney biopsy samples. IgAN was the selected CKD model due to its straightforward diagnosis by standard protocols for histopathological evaluation of kidney biopsies, and to the fact that the renal outcomes are consistently associated with several key pathologic features, including tubular atrophy and interstitial fibrosis. Correlations between PXDN expression and IgAN disease and kidney function parameters as well as with ECM proteins were also explored. Method Fluorescence immunohistochemistry for PXDN was performed in biopsy samples from IgAN patients (n = 20) and in biopsies from healthy kidney donors (n = 7). Proximal tubules were assessed by anti-CD15 fluorescent staining. Collagen III (COLIII) deposition was investigated in IgAN samples (n = 7) by immunofluorescence. Brightfield images were manually segmented into glomeruli, proximal and distal tubules, and interstitium, using QuPath software, and the fluorescence intensity measurements were obtained with ImageJ/Fiji. Results Results showed that, in comparison with healthy kidney samples, PXDN is significantly decreased in proximal and distal tubules of IgAN patients (P &amp;lt; 0.001 and P &amp;lt; 0.05, respectively) whereas it is increased in IgAN interstitium (P &amp;lt; 0.001). When IgAN samples were stratified by the presence or absence of chronic lesions (glomerular sclerosis and interstitial fibrosis) we observed that in the proximal tubules, PXDN is decreased even in areas without lesions while in the distal tubules the expression is compromised only in the lesioned areas. In the interstitium, PXDN shows a tendency of increase from healthy tissue to IgAN in areas without and with tubulointerstitial fibrosis, presenting a significant increase in the lesioned areas (P &amp;lt; 0.001). Concerning ECM deposition, results showed a significant correlation between the expression of PXDN and COLIII in sclerotic glomeruli (R = 0.8214; P = 0.0341) and in the tubulointerstitial fibrotic areas (R = 0.93; P = 0.0067). Moreover, although no differences were observed in the glomerular expression of PXDN between healthy and IgAN samples, when considering eGFR, a significant increase of PXDN was observed in both non-lesioned and sclerotic glomeruli from IgAN patients with eGFR bellow 60 ml/min/1,73 m2. In the interstitium, the expression of PXDN was also increased in tubulointerstitial fibrotic areas of IgAN patients with eGFR bellow 60 ml/min/1,73 m2, in comparison with the same areas in patients with higher eGFR values. Conclusions Overall, our study shows a differential expression of PXDN in IgAN, with loss in the tubular region that relates with the state of interstitial fibrosis, and gain in the glomerular and interstitial region where it correlates with COLIII compartment-specific deposition and with kidney function as assessed by eGFR. These data support, for the first time, the enrollment of PXDN in the topographic mechanism of IgA-mediated kidney lesion that deserves further investigations. Given that sclerosis and fibrosis are a common pathogenic mechanism of CKD, irrespective of the underlying etiology, we postulate that PXDN may serve as a novel therapeutic target for this disease.

Evaluating the Nephroprotective and Hepato-protective Effects of Hypoestes rosea in Acetaminophen-Induced Toxicity in Albino Rats

The leaves of Hypoestes rosea are in use as traditional medicine in the Niger Delta areas in Nigeria and the Western part of Cameroun for the management of different ailments in children, such as anaemia, malaria, fever and other ailments. Regardless of its uses, scanty studies evaluating its organ protective effects exist. Therefore, this research study evaluates the nephroprotective and hepato-protective effects of Hypoestes rosea in acetaminophen-induced toxicity in Albino rats. The objectives of this research study are to evaluate the protective effect of Hypoestes rosea on the kidney and the liver of albino rats. Acetaminophen, which is frequently used as an analgesic and antipyretic drug at high doses, can be harmful to vital organs of the body, affecting the liver and kidneys. In this study, effects of an aqueous extract of Hypoestes rosea (AEHr) on liver function parameters and kidney function parameters of acetaminophen induced-toxicity in albino rats were evaluated using acute (15 days) and sub-chronic (30 days) duration of study and study group comprising of prophylactic (pre-treatment) and therapeutic (post-treatment) phases with six experimental groups in each phase. A total of 112 adult apparently healthy Albino rats weighing (180-220g) were used for this study, divided into six experimental groups of extract control (EC), negative control (NC), positive control (PC), AEHr100mg/kg b w., AEHr 200mg/kg b w., and AEHr 300mg/kg b w. groups each of six rats. At the end of the research study period, blood samples were collected through jugular puncture for liver and kidney function parameters. Results showed that acetaminophen-induced toxicity in albino rats caused toxicity to the kidney and toxicity to the liver, as evidenced by the raised levels of potassium, urea, creatinine and low bicarbonate from the renal function parameters and also as evidenced by significant elevation of bilirubin and liver enzymes with a significantly low total protein and albumin levels from the liver function parameters when compared with other experimental groups. Conversely, AEHr at different concentrations in a dose-dependent pattern at the different treatment phases and different duration periods were able to repair the injury to the kidney and liver caused by acetaminophen induction to normal. Consequently, the findings of this research propose that Hypoestes rosea contains active ingredients accountable for the nephroprotective and hepato-protective abilities in rats and can be recommended for more studies using higher mammals.

Factors Associated with Length of Hospitalization in Patients with Diabetes and Mild COVID-19: Experiences from a Tertiary University Center in Serbia.

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy.