Plasma Creatinine Concentration Research Articles

124 The Acute Effects of Supplementing a Meat-Based Diet with a Combination of Creatine, Carnitine and Choline, Taurine or Methionine on Post-Prandial Plasma Creatine and Creatinine Concentrations in Dogs

Abstract Creatine is an essential nitrogenous compound for cellular energy homeostasis in vertebrates. It is synthesized from the methylation of guanidinoacetate, a metabolite of arginine and glycine. Creatine is found in animal protein, however, when heat-processed for pet food, the creatine content decreases dramatically and creatinine is formed. Previous data from this study have been presented, however, the current objective was to define the postprandial plasma creatine and creatinine response in dogs fed a commercial meat-based diet (CON), top-dressed with a combination of creatine, carnitine and choline (CCC) or other nutrients involved in methyl metabolism, methionine (MET) or taurine (TAU). The control diet contained 0.195 g/kg creatine and 0.563 g/kg creatinine on an as-fed basis. Eight adult Beagles were fed one of the four diets for 7 days in a Latin Square design. On day 7, dogs had cephalic catheters placed and a series of blood samples were collected at fasted and up to 6 hours post-meal. Creatine and creatinine were analyzed using HPLC and data analyzed using Proc Glimmix in SAS (Version 9.4). Plasma creatine concentrations were greater in dogs fed CCC (103±10 µmol/L) compared with MET (72±7 µmol/L) at fasted (P< 0.05) and greater compared with all other treatments from 15 to 360 minutes post-meal (P< 0.05), with a peak concentration of 735±74 µmol/L at 90 min. Plasma creatinine concentrations were greater in dogs fed CCC from 60 to 180 min post-meal compared to all other treatments (P< 0.05), with a peak concentration of 223±13 µmol/L at 90 min. Both peak concentrations were outside of established reference ranges in dogs. These data suggest that when creatine is top-dressed for 7 days, plasma creatine remains increased at fasted and up to 6 hours post-meal, while plasma creatinine remains increased up to 3 hours post-meal, which has implications for energy production and methyl metabolism.

308 Evaluation of Implants and Precision Supplementation on Growth and Muscle Accretion in Beef Steers Post Weaning

Abstract Backgrounding or stocker operations attempt to add value to calves by efficiently adding weight and predominately taking advantage of the protein accretion phase of development, ultimately preparing calves for later stages of production. The objective of the current study was to evaluate the effects of an implant (Revalor-G) or implant plus supplementation on protein accretion patterns in backgrounded beef steers. A 56-day backgrounding study was conducted using Angus-based steers (n = 69; initial BW 233 ± 29 kg) grazing a cow pea and millet mixture. Steers were randomly assigned to one of three treatments (n = 23 steers per treatment): 1) grazing only (G), 2) grazing with implant (GI), or 3) grazing with implant plus individual animal supplementation via Super Smart Feeder at 0.75% BW (GIS). Steers were weighed and blood was collected every 14 days to determine plasma blood urea nitrogen (BUN) and creatinine concentrations. Ultrasound measurements of ribeye area and backfat were collected at days 0, 28, and 56 of study. Data were analyzed using the GLIMMIX function of SAS version 9.4. GIS steers had a greater (P ≤ 0.0004) body weight change than GI or G steers. GI and GIS steers had a greater (P ≤ 0.0117) ribeye area compared with G steers. GI steers had a greater (P < 0.0180) ribeye area to body weight ratio than G steers. When evaluating blood parameters, GI steers had a greater (P< 0.0009) plasma BUN concentration than GIS steers. No treatment differences were observed for plasma creatinine concentrations. G and GI steers had a greater (P ≤ 0.0290) BUN to creatinine ratio than GIS steers. Results of this study suggest that implanted steers may require additional supplementation to optimize growth and muscle accretion.

The in-vivo diuretic activity of methanolic extract of Quercus leucotrichophora A. Camus seeds

IntroductionTraditional healers' assertions that Quercus leucotrichophora A. Camus is a plant that has been used in traditional medicine to treat various urinary and renal diseases, thus the present study aims to investigate the diuretic activity of the methanolic extract of seeds in rats. MethodsDried course powder was extracted with methanol using soxhlet extraction. Male Wistar rats were given a control (normal saline, 15 ml), a reference medication (furosemide, 13 mg/kg), and three separate doses (250 mg/kg, 375 mg/kg, and 500 mg/kg) of the extract orally. Urine volume, urinary electrolytes, urine pH, and conductivity were measured to establish the extract's diuretic activity. The urine outflow was tested at 6, 12, and 24 h, as well as electrolyte content, pH, and conductivity. Creatinine, urea, aldosterone, and electrolyte concentrations in plasma and urine samples were also determined. The index kidney function was determined by analyzing kidney homogenate. One-way ANOVA was used to evaluate the data. ResultsThe findings demonstrated that the extract increased diuresis in a dose-dependent manner, i.e., at 500 mg/kg, the extract exhibited significant diuretic effects (p < 0.001) as compared to the reference medicine, furosemide. The urinary excretion of Na+, K+, and Cl− was also significantly increased (p < 0.001) at all doses. The effectiveness of the extract as a diuretic was further established by biochemical analysis. These results confirm the historic usage of the herb as a diuretic and the importance of maintaining indigenous knowledge. ConclusionCollectively, the data provided here indicated that using a methanolic extract of Quercus leucotrichophora seeds to cause diuresis is a viable option.

Safety, Efficacy, and Relapse of Nirmatrelvir-Ritonavir in Kidney Transplant Recipients Infected With SARS-CoV-2

IntroductionThe efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs).MethodsIn this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied.ResultsA total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads.ConclusionNR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.

Effect of guanidinoacetic acid supplementation on nitrogen retention and methionine methyl group flux in growing steers fed corn-based diets.

Six ruminally cannulated Holstein steers (256 ± 14 kg) were used in a 6 × 6 Latin square design to assess effects of guanidinoacetic acid (GAA) supplementation on N retention and methionine (Met) methyl group flux in growing cattle fed corn-based diets. Factorial treatments were two levels of Met (0 or 5 g/d) and three levels of GAA (0, 7.5, or 15 g/d) delivered by continuous abomasal infusion. Periods were 10 d in length and included 6 d of treatment adaptation, 3 d for total fecal and urine collections, and 1 d for blood sampling and flux measurements. Urinary N linearly increased (P < 0.01) with GAA supplementation and decreased (P < 0.05) with Met supplementation. Fecal N excretion was unaffected (P ≥ 0.42) by treatment. Retained N was not affected by GAA supplementation, but it was increased (P < 0.01) by Met supplementation. Use of methionine for transmethylation reactions, as well remethylation of homocysteine, was not affected by GAA supplementation when Met was not supplemented, but tended to be linearly increased by GAA supplementation when Met was supplemented (GAA-linear × Met interaction; P = 0.07), with the increases matching the amount of GAA provided. This response suggests that methylation reactions for compounds other than GAA were reduced by GAA supplementation when Met supply was deficient. Plasma concentrations and urinary excretion of creatine increased linearly (P = 0.03 and P = 0.06, respectively) when GAA was supplemented. There was a linear increase (P < 0.01) in urinary GAA excretion with GAA supplementation. Neither plasma concentration nor urinary excretion of creatinine was affected (P ≥ 0.17) by treatment. No treatment differences (P ≥ 0.13) were observed for plasma haptoglobin concentrations. Plasma urea-N linearly increased (P < 0.05) with GAA supplementation. Concentrations of Met and taurine increased (P < 0.05) when Met was supplemented. Plasma arginine was greatest at the intermediate level of supplemental GAA (quadratic, P < 0.05). The increase in N retention when Met was supplemented demonstrates Met was limiting in the corn-based diet. Supplementation of GAA alone or with Met as a methyl donor did not increase N retention in growing steers, perhaps because creatine production was favored over protein deposition as a use for Met.

Effect of Methanolic Extract of Carica papaya Seed on Renal Function and Antioxidant Activities Following Ibuprofen-induced Toxicity on Male Wistar Rats

In this study, the effect of methanolic seed extract of Carica papaya (MSECP) was investigated to ascertain its effect on the renal function and antioxidants activities following ibuprofen induced renal toxicity. Phytochemical screening of crude extract revealed the presence of alkaloids, flavonoids, glycosides, saponins and tannins while anthraquinone and phlobatannins were found to be absent. Thirty (30) healthy male Wistar rats were divided into 5 groups. Group A (received feed and water only); Group B received 80mg/kg of ibuprofen only; Group C received 80mg/kg of ibuprofen + 150mg/kg of MSECP; Group D received 80mg/kg of ibuprofen + 300mg/kg of MSECP; Group E (received 80mg/kg of ibuprofen and treated with 600mg/kg of (MSECP). The administration of the extract lasted for 21 days within hours of 7-8 am via oral gavage. After 21 days the animals were anesthetized with 25% Urethane and blood was collected using a heparinized capillary tube and transferred into a plain container and centrifuged. The serum retrieved was used to assay serum antioxidants Superoxide dismutase (SOD), Catalase activity (CAT), Glutathione (GSH), Glutathione peroxidase (GPX), Total Antioxidant capacity (TAC) and kidney enzymes (urea and creatinine). MSECP significantly reduced the plasma concentration of urea and creatinine (p&gt;0.05) when compared to group A. The antioxidant enzymes reduced significantly (p&gt;0.05) in groups that was administered with MSECP when compared to the group A and B. MSECP was discovered to have some therapeutic effect on renal function probably as a result of some of the antioxidants and phytonutrients present in Carica papaya which have the capability of increasing glomerular filtration of toxic substances from the kidney and hence recommend that Carica papaya seed could be included in our daily diet.

Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats.

BackgroundIn people and dogs, torasemide has higher bioavailability, longer half‐life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited.ObjectiveTo assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin‐angiotensin‐aldosterone system (RAAS).AnimalsSix clinically healthy adult European shorthair cats.MethodsRandomized 4‐period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model.ResultsMean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half‐life was 12.9 hours. Urine output significantly increased after torasemide administration (P < .001). The urine sodium : potassium ratio (uNa : uK) paralleled and was statistically correlated to urine output (P < .001). Administration of a single torasemide dose led to a significant dose‐dependent increase in urine aldosterone : creatinine ratio (uAldo : C; P < .001) and a transient decrease in plasma potassium concentration (P < .001) but did not affect blood pressure or plasma creatinine concentration.Conclusions and Clinical ImportanceA single torasemide dose leads to a significant increase in diuresis and renin‐angiotensin‐aldosterone system (RAAS) activation in healthy cats, with high absolute bioavailability, and without clinically relevant adverse effects. Pharmacokinetic parameters indicate that once daily dosing of 0.27 mg/kg may be appropriate in a clinical setting.

Modulation of diabetic kidney disease markers by an antagonist of p75NTR in streptozotocin-treated mice

Two therapeutic agents targeting p75NTR pathways have been recently developed to alleviate retinopathy and bladder dysfunction in diabetes mellitus (DM), namely the small molecule p75NTR antagonist THX-B and a monoclonal antibody (mAb) that neutralizes the receptor ligand proNGF. We herein explore these two components in the context of diabetic kidney disease (DKD).Streptozotocin-injected mice were treated for 4 weeks with THX-B or anti-proNGF mAb. Kidneys were taken for quantification of microRNAs and mRNAs by RT-qPCR and for detection of proteins by immunohistochemistry, immunoblotting and ELISA. Blood was sampled to measure plasma levels of urea, creatinine, and albumin. DM led to increases in plasma concentrations of urea and creatinine and decreases in plasma albumin. Receptor p75NTR was expressed in kidneys and its expression was decreased by DM. All these changes were reversed by THX-B treatment while the effect of mAb was less pronounced. MicroRNAs tightly linked to DKD (miR-21-5p, miR-214-3p and miR-342-3p) were highly expressed in diabetic kidneys compared to healthy ones. Also, miR-146a, a marker of kidney inflammation, and mRNA levels of Fn-1 and Nphs, two markers of fibrosis and inflammation, were elevated in DM. Treatments with THX-B or mAb partially or completely reduced the expression of the aforementioned microRNAs and mRNAs. P75NTR antagonism and proNGF mAb might constitute new therapeutic tools to treat or slow down the progression of kidney disease in DM, along with other diabetic related complications. The translational potential of these strategies is currently being investigated.

Nephrotoxic evaluation of ethanol stem bark extract of Dialium guineense in normal wistar rats

The present study was undertaken to investigate the nephrotoxic effect of ethanol extract of Dialium guineense stem bark in normal Wistar albino rats. Thirty-five male rats were assigned to seven (7) groups (5 rats per group). One group served as control, while graded doses of the extract (200 - 5000 mg/kg body weight, bwt) were administered to the test rats daily for twenty-eight days. The control rats received distilled water. Thereafter plasma concentrations of creatinine, urea, electrolytes and urease activity were measured. There were no significant differences in the concentrations of the measured renal parameters before and after treatment, among the groups (p > 0.05). These results indicate that ethanol extract of the medicinal plant stem bark may be relatively safe. However, further studies spanning several months may be necessary.

Effects of Irvingia grandifolia on the Plasma Concentration of Urea, Creatinine and White Blood Cells Count (Total &amp; Differential) in Normal Rabbits

The hypoglycemic effects of Irvingia grandifolia is documented. While medicinal plant may have recognizable therapeutic effect, it may also have few toxic side-effects. The use of Irvingia grandifolia has been found to be effective in the management of diabetes mellitus but the effect of this herb on plasma urea, creatinine concentrations and white blood cell count has not been studied so far. The effect was investigated and found out that there is no damaging effect of the herb on plasma creatinine concentration based on student distribution (t-test) on the treated animals. Also, there is no significant effect of the herb extract on plasma urea concentration, white blood cell count (total and differential) also found from student distribution (t-test) after comparing treated animals with control animals.

Arginine supplementation in the feed of gestating sows

The high prolificacy achieved by the genetic improvement of sows has resulted in decreased birth weights and uniformity of litters, as well as increased prenatal and preweaning mortality. Amino acids, such as arginine, are essential for the proper development of the placenta and the swine fetus. Their role include regulating angiogenesis, vascular development, and therefore potentially placental vascularization, providing a greater supply of nutrients and oxygen from the sow to the fetuses. The objective of the trial was to evaluate the effects of dietary l-arginine supplementation on the reproductive and productive performance of gestating sows from days 30 to 60 and days 80 to 114 of gestation. Forty-eight pluriparous sows with two to six parities were divided into two different treatments with a total of 24 replicates per treatment. The treatments consisted of a control diet without l-arginine supplementation (CON) and a diet with top-dressed supplementation of 1.0% l-arginine (ARG). Blood samples were collected from the sows on days 30, 60, 90, and 114 of gestation to determine the plasma concentrations of albumin, creatinine, and urea. Sows were weighed 24 h after farrowing and at weaning to calculate body weight loss during lactation. Piglets were individually weighed at birth before the first feeding and at weaning. Supplementation of the diet with l-arginine during gestation affected (p = 0.025) the plasma concentrations of triglycerides at 60 days, but it did not impact the albumin, creatinine, and urea's concentrations at 30, 60, 90, and 114 days of gestation. However, the concentrations of creatinine differed (p = 0.006) for gestational periods. The average weight of piglets born alive was greater (p = 0.0485) for ARG compared to CON and the other performance and reproductive characteristics did not differ. The percentage of piglets born weighing over 1.81 kg was greater (p < 0.05) for sows fed ARG than in CON fed sows. l-arginine supplementation in the feed of gestating sows increased the average weight of piglets born alive and the percentage of piglets with a birth weight above 1.81 kg, reduced the concentration of triglycerides at 60 days of gestation, and the gestational period had effect about the creatinine concentrations.

Body, metabolic and renal changes following cross-sex estrogen/progestogen therapy in a rodent model simulating its use by transwomen.

The use of sex steroids by trans people has been of paramount importance regarding body changes during gender transition. The objective of this study was to assess the effects of an injectable steroid combination frequently used by transwomen, namely estradiol enanthate with dihydroxyprogesterone acetophenide (E2EN/DHPA), on blood pressure and metabolic outcomes using an animal model. Two-month-old male Wistar rats were orchiectomized or sham-operated and divided into groups: (1) Sham treated with sesame oil vehicle (SG), (2) sham treated with E2EN/DHPA (SP), (3) orchiectomized rats treated with vehicle (OG), and (4) orchiectomized rats treated with E2EN/DHPA (OP), with all groups treated every 10days for 5 months. We evaluated systolic blood pressure (SBP), body weight (BW), abdominal circumference, nasoanal length (NAL), food and water intake (FI, WI), lipid profile (triglycerides, LDL, and HDL), serum C-reactive protein (CRP), plasma concentrations of urea (URpl) and creatinine (CRpl), 24h urinary volume (V24h), sodium and potassium excretion (UNa+, UK+), and proteinuria. E2EN/DHPA administration reduced BW (SP 324.5 ± 31.1; OP 291.7 ± 41.3g) and NAL (SP 24.5 ± 0.4; OP 24.6 ± 1.0cm), without changing blood pressure, but increased URpl concentration (SP 55.0 ± 4.8; OP 42.5 ± 8.8mg/dL) and CRpl (SP 0.47 ± 0.05; OP 0.46 ± 0.04mg/dL), sodium (SP 3.1 ± 0.8; OP 3.3 ± 0.4µEq/min/kg), potassium (SP 0.91 ± 0.22; OP 0.94 ± 0.22µEq/min/kg) excretions and urinary volume (SP 15.5 ± 2.1; OP 16.4 ± 2.9mL/24h). Cross-sex hormone therapy with E2EN/DHPA significantly modified body characteristics in male rats, producing a feminizing change without altering blood pressure or generating harmful metabolic parameters, but larger translational studies are still needed.

Renal Transporter-Mediated Drug-Biomarker Interactions of the Endogenous Substrates Creatinine and N1 -Methylnicotinamide: A PBPK Modeling Approach.

Endogenous biomarkers for transporter-mediated drug-drug interaction (DDI) predictions represent a promising approach to facilitate and improve conventional DDI investigations in clinical studies. This approach requires high sensitivity and specificity of biomarkers for the targets of interest (e.g., transport proteins), as well as rigorous characterization of their kinetics, which can be accomplished utilizing physiologically-based pharmacokinetic (PBPK) modeling. Therefore, the objective of this study was to develop PBPK models of the endogenous organic cation transporter (OCT)2 and multidrug and toxin extrusion protein (MATE)1 substrates creatinine and N1 -methylnicotinamide (NMN). Additionally, this study aimed to predict kinetic changes of the biomarkers during administration of the OCT2 and MATE1 perpetrator drugs trimethoprim, pyrimethamine, and cimetidine. Whole-body PBPK models of creatinine and NMN were developed utilizing studies investigating creatinine or NMN exogenous administration and endogenous synthesis. The newly developed models accurately describe and predict observed plasma concentration-time profiles and urinary excretion of both biomarkers. Subsequently, models were coupled to the previously built and evaluated perpetrator models of trimethoprim, pyrimethamine, and cimetidine for interaction predictions. Increased creatinine plasma concentrations and decreased urinary excretion during the drug-biomarker interactions with trimethoprim, pyrimethamine, and cimetidine were well-described. An additional inhibition of NMN synthesis by trimethoprim and pyrimethamine was hypothesized, improving NMN plasma and urine interaction predictions. To summarize, whole-body PBPK models of creatinine and NMN were built and evaluated to better assess creatinine and NMN kinetics while uncovering knowledge gaps for future research. The models can support investigations of renal transporter-mediated DDIs during drug development.

Influence of Vitamin D Supplement on Immune Function of the Older Healthy People: A Pilot Randomised Control Trial

Abstract Objectives The study aims to investigate the influence of vitamin D (VD) supplement on immune function of the healthy older people. Methods Designed as a randomized control trial, 21 participants (55–85) years old took part and completed the study (20 White, 1 Indian) during May-November 2018 in Coventry, England. The participants were randomized into two groups, VD and control, stratified by age, gender and body mass index (BMI). The VD group (n = 11) took VD3 of 25 μg/day for 12 weeks, while the control group (n = 9) were only provided with educational information of VD. At baseline, 6 weeks and 12 weeks, plasma 25(OH)D levels and immune parameters including phagocytic activity of granulocytes and monocytes, tumour necrosis factor (TNF), interleukin 6 (IL-6), lymphocyte subsets (Th, Tc and natural killer cells), and fast blood glucose and lipid were measured. Dietary VD intake was analysed at baseline and week 12. The data were presented as mean ± standard error (SE) and analysed by two-way repeated measures ANOVA. Results The average age of the participants was (65.8 ± 1.7) years old (67.4 ± 2.7 in VD group and 64.5 ± 2.2 in control group). At baseline, 42.9% of the participants were VD deficiency (25(OH)D &amp;lt; 30 nmol/L), only 10% achieved a level of 25(OH)D &amp;gt; 50 nmol/L. There was a significant increase in plasma 25(OH)D concentration in VD group compared with that in the control group (visit*treatment effect p = 0.002). The level of 25(OH)D in the VD group was increased rapidly at 6 weeks (from 38.4 ± 8.7 nmol/L at baseline to 51.0 ± 9.3 nmol/L) and little change has been observed at 12 weeks (51.8 ± 8.6 nmol/L). There was a significant visit*treatment effect (p = 0.036) on the plasma creatinine concentration between two groups, indicating a decrease of plasma creatinine concentration in VD group (from 79.8 ± 7.0 μmol/L at baseline to 75.1 ± 5.4 μmol/L at week 12). There was a significant correlation between body mass index (BMI) and 25(OH)D concentration (P &amp;lt; 0.001). There was no significant effect of VD supplementation on parameters of immune function. Conclusions VD deficiency is common among this older population even during the summertime. VD supplementation at 25 μg/day for 12 weeks showed an anti-inflammatory effect. Funding Sources Coventry University.

Continuous Infusion of Iohexol to Monitor Perioperative Glomerular Filtration Rate.

Continuous monitoring of the glomerular filtration rate (GFR) in the perioperative setting could provide valuable information about acute kidney injury risk for both clinical and research purposes. This pilot study aimed to demonstrate that GFR measurement by a continuous 72 hrs iohexol infusion in patients undergoing colorectal cancer surgery is feasible. Four patients undergoing robot-assisted colorectal cancer surgery were recruited from elective surgery listings. GFR was determined preoperatively by the single-sample iohexol clearance method, and postoperatively at timed intervals by a continuous iohexol infusion for 72 hrs. Plasma concentrations of creatinine and cystatin C were measured concurrently. GFR was calculated as (iohexol infusion rate (mg/min))/(plasma iohexol concentration (mg/mL)). The association of the three different filtration markers and GFR with time were analysed in generalized additive mixed models. The continuous infusion of iohexol was established in all four patients and maintained throughout the study period without interfering with ordinary postoperative care. Postoperative GFR at 2 hours were elevated compared to the preoperative measurements for patients 1, 2, and 3, but not for patient 4. Whereas patients 1, 2, and 3 had u-shaped postoperative mGFR curves, patient 4 demonstrated a linear increase in mGFR with time. We conclude that obtaining continuous measurements of GFR in the postoperative setting is feasible and can detect variations in GFR. The method can be used as a tool to track perioperative changes in renal function.

EXPERIMENTAL MODEL OF NEPHROPATHY IN RATS WITH PROLONGED ANTIMONY INTOXICATION

Introduction. Despite the ample prevalence of antimony in the human environment, there are still no reliable data on its nephrotoxicity. Data from the literature are inconsistent. Materials and methods. The experiments were performed in 2 groups of male Wistar rats weighing 200-250 g. Group 1: intact animals; Group 2: animals with intragastric injection of antimony chloride solution. The solution was injected through a probe into the stomach every day at a dose of 3 mg/kg for one and two months. After the experiment was terminated, the rats were euthanised under thiopental anaesthesia for plasma and renal tissue examination. The basic processes of urine formation, blood electrolyte content (sodium, potassium and calcium) and kidney function were studied under conditions of spontaneous 6-hour diuresis after one and two months. Content of sodium and potassium in biological material was determined by ion-selective method on electrolyte analyzer AEK-1 (Kverti-Med). The concentration of calcium and creatinine in urine and blood plasma, total protein in urine were determined spectrophotometrically. For histological studies, kidney tissue samples were fixed in 10% neutral formalin, then embedded in paraffin, followed by preparation of 7-8 microns thick sections. The sections were stained with hematoxylin and eosin. The sections were studied in transmitted light using a Mikmed-1 microscope at a magnification of 80x200x400. Results. Experiments showed that chronic sulimic intoxication leads to toxic nephropathy, manifested after 2 months of intoxication by a sharp decrease in diuresis due to decreased glomerular filtration rate, impaired electrolyte-excretory function of the kidneys, proteinuria. Morphological examination showed alterative changes: urinary space of glomeruli was enlarged, capillary endothelium with signs of hydropic dystrophy. There was hyaline-drop dystrophy of renal tubule epithelium with partial necrosis. Stroma was edematous, vessels were full of blood with hyalinosis of their walls. Conclusion. Prolonged antimony intoxication leads to nephropathy. Manifestations of the latter after one month and two months of intoxication differ in direction, but are accompanied by marked proteinuria.

Hyperuricemia in addition to GRACE Score improves risk stratification in acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: None. Background Uric acid (UA) is a risk factor for coronary artery disease, and it might be a predictor of outcomes in patients (P) with acute coronary syndromes (ACS). Global Registry of Acute Coronary Events (GRACE) Score is an extensively validated tool for risk stratification in these P. The aim of this study is to evaluate the impact of hyperuricemia (HU) in the prognosis of ACS and compare it with the GRACE Score. Methods This study included all P admitted for ACS between 2007 and 2015 in a Cardiology Department. HU was defined as admission UA levels &amp;gt; 6 mg/dL. In-hospital mortality and all-cause mortality at 12 months after discharge were assessed. Chi-square and Mann-Whitney U tests were used for group comparisons; survival analysis used Kaplan-Meier curves and log-rank tests; and subgroup analysis was performed with an unadjusted Cox model. Results 959 P were included (mean age 67.7±12.8y, 71.1% male). HU occurred in 498 P (51.9%). Its presence was associated with older age (p&amp;lt;0.001); male sex (p=0.034); arterial hypertension (p&amp;lt;0.001); obesity (p=0.006) and chronic kidney disease (p=0.025). At admission, P with HU had higher heart rate (p=0.003); higher Killip-Kimball class (p=0.001); higher plasma concentrations of creatinine (p&amp;lt;0.001), C-reactive protein (p=0.003), blood natriuretic peptide (p=0.010) and triglycerides (p&amp;lt;0.001); and lower high-density lipoprotein cholesterol levels (p&amp;lt;0.001). HU was also associated with conservative treatment of ACS (p=0.005), left main disease (p=0.037) and longer length of hospital stay (p=0.009). Univariate logistic regression analysis showed that HU was a predictor of in-hospital mortality (OR 2.048; 95% CI 1.048-4.005; p=0.036). During the follow-up, P with HU had a significantly decreased survival than P with normal UA levels (Kaplan-Meier x²=8.25; p=0.004). In subgroup analysis, the effect of HU in survival was consistent among P stratified based on gender, age and comorbidities. When P were classified according to serum UA levels and GRACE Score, a progressive decline in survival was found in P without HU and GRACE score≤140, P with HU and GRACE score≤140, P without HU and GRACE score&amp;gt;140, and P with HU and GRACE score&amp;gt;140 (Kaplan-Meier χ²=24.17; p&amp;lt;0.001) - graph 1. Conclusions In this study, HU was associated with in-hospital and 12-month follow-up mortality. Its use may allow a better risk stratification in P with ACS, particularly when combined with the most widely used tool, the GRACE score.

Creatinine as a Urinary Marker of the Purine Derivatives Excretion in Urine Spot Samples of Lambs Fed Peach Palm Meal.

Simple SummaryExperimental trials designed to predict the microbial protein synthesis in the rumen via urinary purine derivatives require access to 24-h urinary volumes. This technique is non-invasive but requires access to 24-h urinary volumes, which is impracticable in grazing animals or a large number of feedlot sheep. The challenge is to provide the possibility of using the purine derivatives and creatinine concentrations in a spot urine sample and the daily creatinine excretion in urine as accurate estimators of purine derivatives’ excretion per day.The objective was to evaluate the influence of diets on lambs using different levels of peach palm meal as a replacement for maize (0, 10, 40, 60, and 85% of diet dry matter) on the endogenous creatinine clearance (CC), urine concentration ratio of purine derivatives to creatinine (PDC index), and daily creatinine excretion (DCE) as a marker to estimate purine derivatives (PD) excretion from urinary spot samples collected at different time points (4, 8, 12, 16, 20, 24 h after morning feeding) compared to 24-h total urine collection. The measured parameters were voluntary intake, urinary volume, CC, DCE, the concentration of plasma creatinine, and PD and purine derivatives’ excretion (PDE). Five lambs were allocated to metabolic cages and distributed in a 5 × 5 Latin square. Urine collection was taken daily on days 16 to 19 of each experimental period. The inclusion of peach palm meal linearly reduced the intake of dry matter (g kg BW−0.75, p = 0.005), crude protein (g kg BW−0.75, p = 0.010), metabolizable energy (MJ kg BW−0.75, p = 0.010) and CC (p < 0.0001). It also quadratically affected the urinary volume (p = 0.008) and DCE (p = 0.004). There was a linear decrease for PDC index (p = 0.032) and PDE (p < 0.0001) measured in the 24-h total urine with peach palm meal levels. The different times of spot urine sampling did not affect (p > 0.05) the PDC index and PDE. Peach palm meal decreases the CC thereby compromising the use of a mean value of DCE as a PDE marker in spot urine samples. There is greater accuracy when using different values of DCE obtained for each diet as markers for the PDE in spot urine samples. Unconventional foodstuffs of low palatability affecting the voluntary intake of feed change the renal function.

MO269: The Frequency and Aetiology of Repeated Acute Kidney Injury Episodes Determines the Degree of Renal Damage

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) is the most serious health problem and constitutes the 16th leading cause of death worldwide. Multiple studies have identified acute kidney injury (AKI) as a risk factor for the development and progression of CKD [1]. Despite extensive investigation of AKI and CKD in experimental models, the underlying mechanisms of the transition from AKI to CKD remain unclear. It is known that after an AKI episode, maladaptive responses may occur resulting in structural and fuctional abnormalities as parenchymal inflammation, tubular cell death, accumulation of extracellular matrix, and decreased glomerular filtration rate, among others [2]. We hypothesized that after the combination of different renal insults, the mechanisms of adaptative repair could be less effective causing renal structural abnormalities that might not be detected by common clinical parameters but could lead to CKD. METHOD We used 8-week-old, male Wistar rats. Animals were divided into four experimental groups: ‘Control’ group: SHAM-operated rats, which received saline solution, i.p.; ‘CDDP5-I/R’ group: 5 mg/kg cisplatin i.p., and after renal function normalization, 60-min ischemia-reperfusion to the left kidney; ‘Ctrl-I/R-I/R’ group: 60-minute renal ischemia-reperfusion to the left kidney, and 2 weeks later 60-min ischemia-reperfusion to the right kidney; ‘CDDP5-Ctrl-I/R’ group: 5 mg/kg cisplatin i.p, and 2 weeks after renal function normalization, 60-min ischemia-reperfusion. Blood and urine samples were collected at: day 0 (basal); day 4 (AKI development); day 8 (normalized renal function); day 9 (1 day after ischemia); days 56 and 90. Renal function was analyzed through the levels of plasma creatinine concentration (pCr), creatinine clearance, blood urea nitrogen and proteinuria, which were measured with colorimetric methods. Animals were sacrificed at days 56 and 90. Tissue samples were stained with Masson's trichrome, Sirius Red, Periodic Acid Schiff and Hematoxylin-–Eosin for histological analysis. RESULTS The combination of different experimental AKI episodes and the timeframe between those episodes were related to the extent of renal structural alterations, even though renal function was apparently normal. The ‘CDDP5-Ctrl-I/R’ group presented the highest level of structural abnormalities. In addition, in those groups in which an AKI was induced by CDDP5, more structural damage was detected than in the ‘Ctrl-I/R-I/R’ group. CONCLUSION The frequency of AKI episodes, the kind of insult and their combination determine the amount and degree of tissue damage which, however, is not correlated with a decline in renal function (determined by pCr or creatinine clearance, blood urea nitrogen or proteinuria). These subclinical alterations might be related to a poor prognosis and are a risk factor for the progression of CKD; therefore, new tools to determine renal function are needed to prevent the progression and mortality of the disease.

Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Women With a History of Gestational Diabetes

Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease as their age‐matched counterparts. GDM is associated with endothelial dysfunction and elevated oxidative stress during pregnancy, and vascular dysfunction postpartum. However, the mechanism(s) mediating this postpartum dysfunction are unknown. Using the cutaneous circulation as a model, we examined if oxidative stress contributes to microvascular dysfunction in healthy women with a history of GDM (GDM). We hypothesized that: 1) endothelium‐ and nitric oxide (NO)‐dependent dilation would be attenuated in GDM compared to women with a history of normal pregnancy (NP), and 2) local antioxidant (L‐ascorbate) administration would augment endothelium‐ and NO‐dependent dilation in GDM. Ten NP (35±1yrs) and 10 GDM (34±1yrs) underwent a standard local heating protocol (42°C; 0.1°C·s‐1). Two intradermal microdialysis fibers were placed in the ventral forearm for local delivery of lactated Ringer’s (control), or 5mM ascorbate. After full expression of the local heating response, 15mM NG‐nitro‐L‐arginine methyl ester (L‐NAME; NO synthase‐inhibition) was perfused. Red cell flux was measured continuously by laser‐Doppler flowmetry and cutaneous vascular conductance (CVC=flux/MAP) was standardized to maximum (%CVCmax; 28mM SNP + 43°C). Urine albumin to creatinine ratio (ACR) and plasma concentrations of oxidized LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) were measured. Women with history of GDM had attenuated endothelium‐dependent (GDM: 67±7 vs. NP: 90±4%CVCmax; p&lt;0.001) and NO‐dependent (GDM: 54±7 vs. NP: 71±3%; p=0.001) dilation at the control site and tended to have higher urine ACR (p=0.06). Both endothelium‐dependent (r2=0.53, p=0.02) and NO‐dependent (r2=0.56, p=0.01) dilation were related to urine ACR in GDM. Local ascorbate perfusion improved endothelium‐dependent (82±5%CVCmax; p=0.03 vs. control) and NO‐dependent (68±5%; p=0.02 vs. control) dilation in those with history of GDM but had no effect in HC (p&gt;0.05). There were no differences in plasma oxLDL (hxGDM:60.5 vs hxNP:50.9 U/L; p=0.18) or TBARS (hxGDM: 0.3 vs hxNP: 0.2 μM; p=0.26) concentrations between groups. These data suggest that otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and that this dysfunction is mediated, in part, by oxidative stress at the level of the vasculature.