Creatinine Assay Research Articles

An Evaluation of a Point-of-Care GEM Premier ChemSTAT Analyzer in an Emergency Department: Prevention of Contrast-Induced Nephropathy and Optimization of Patient Flow.

Background: Having a laboratory renal profile for medical imaging examinations requiring contrast media (CM) administration is strongly advised. Creatinine helps identify patients at risk of contrast-induced nephropathy (CIN). The GEM® Premier™ ChemSTAT (Werfen) is a point-of-care (POC) analyzer with 12 emergency parameters, including a creatinine assay. This study aims to compare ChemSTAT with the central analytical solution of the University Hospital of Clermont-Ferrand and to evaluate the interest in using POC creatinine in the emergency department (ED) to optimize the flow of patients, especially when CM administration is necessary. Methods: More than 200 whole blood (WB) samples from the ED were evaluated on the ChemSTAT analyzer. As comparative methods, the plasma aliquots from the same samples were assayed on an Atellica® CH (Siemens Healthineers). The clinical concordance was assessed according to the decision cut-offs of the French Society of Radiology for the risk of CIN. The availability times of biological results between ChemSTAT and the central laboratory were studied. Results: WB results from the ChemSTAT analyzer correlated well with those from the Atellica® CH, except for tCO2 (the known bias between the Siemens and Cobas Roche methods for predicting ChemSTAT values). The results of the creatinine assay allow for identical medical decisions in comparison to the renal-risk cut-offs. The availability of the biological results was reduced by 50 min on average with ChemSTAT vs the central laboratory. Computed tomography (CT) was performed for 44.7% of patients, including the injection of the CM in 68% of cases. For these patients, the availability of creatinine results relative to imaging time is faster with the ChemSTAT by an average of 45.2 min. Conclusions: Great analytical and clinical correlations for creatinine assays allow for the safe identification of patients at risk of CIN, and improve patient flow in ED, especially for those requiring computed tomography with CM.

Discordance between creatinine and cystatin C-based estimation of glomerular filtration rate (eGFR) in solid organ transplant recipients

BackgroundEstimation of glomerular filtration rate is a critical component of assessing kidney function post-solid organ transplantation and in monitoring risk of acute injury. Our objective was to evaluate estimated glomerular filtration rate (eGFR) as derived from creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) in a cohort of transplant recipients. MethodsA total of 47 unique post-solid organ transplant patients receiving tacrolimus were included. Residual specimens were assayed for creatinine (Jaffe and enzymatic), cystatin C, and tacrolimus. eGFR was estimated using the 2021 CKD-EPI formulae. Results were compared by Deming regression and bias was assessed using non-parametric cumulative distribution plots. Percent agreement in chronic kidney disease (CKD) by stage was evaluated across equations. ResultseGFRcys relative to eGFRcr estimates demonstrated a median bias of –22 mL/min/1.73 m2 and an overall 21.3 % [95 % CI: 12.1, 35.0] agreement in CKD staging. eGFRcr-cys demonstrated a median bias of −14 mL/min/1.73 m2 and overall agreement of 34.0 % [95 % CI: 22.3, 48.4] relative to eGFRcr (enzymatic). Discordance increased proportionally with eGFR and did not differ by creatinine assay (Jaffe or enzymatic). ConclusionCystatin C incorporation leads to markedly negative biases between eGFR estimates in patients with solid organ transplant, implying lack of applicability of eGFRcys or GFRcr-cys in the transplant setting. This highlights the dependency of patient characteristics on equation performance and the need to consider confounding factors in interpretation and utilization of cystatin C based equations.

Moving forward from Cockcroft-Gault creatinine clearance to race-free estimated glomerular filtration rate to improve medication-related decision-making in adults across healthcare settings: A consensus of the National Kidney Foundation Workgroup for Implementation of Race-Free eGFR-Based Medication-Related Decisions

Abstract Purpose The goals of this paper are to (1) provide evidence and expert consensus to support a unified approach to estimating kidney filtration in adults with stable kidney function using race-free estimated glomerular filtration rate (eGFR) in place of Cockcroft-Gault estimated creatinine clearance (C-G eCrCL) for medical and medication-related decisions, and (2) demonstrate how adjusting eGFR results for an individual’s body surface area (BSA) when it is higher or lower than 1.73 m2 will improve results for medication-related decisions. Summary C-G eCrCL is predominantly used by US pharmacists to determine eGFR for the purposes of medication-related decisions, even though more accurate eGFR equations exist. Several driving factors make it the ideal time to shift clinical practice from using C-G eCrCL to eGFR. These factors include the following: (1) 2024 Food and Drug Administration (FDA) guidance for industry recommends eGFR over C-G eCrCL to evaluate the impact on pharmacokinetics in patients with impaired kidney function; (2) a joint National Kidney Foundation (NKF) and American Society of Nephrology task force recommends 3 race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR equations for medical and medication-related decision-making; (3) the almost ubiquitous use of standardized serum creatinine assay methods in US clinical laboratories; and (4) increasing availability and use of serum cystatin C for eGFR assessment. This publication guides practitioners through the rationale for using race-free eGFR equations for medication-related decisions and how to implement this practice change. Conclusion The NKF Workgroup for Implementation of Race-Free eGFR-Based Medication-Related Decisions suggests that health systems, health settings, clinical laboratories, electronic health record systems, compendia and data vendors, and healthcare practitioners involved with medication-related decision-making transition away from C-G eCrCL and towards the race-free eGFR equations for more accurate assessment of kidney filtration and consistency in medication and medical decision-making across the US.

Harmonized Tubular Maximum Phosphate Reabsorption per Glomerular Filtration Rate (TmP/GFR) reporting in adults and children in Australia and New Zealand

Abstract Tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is a key diagnostic test for renal phosphate wasting. However, there is a lack of international consensus regarding the reporting of age-related reference intervals. The TmP/GFR Harmonization Working Group, formed by The Australasian Association for Clinical Biochemistry and Laboratory Medicine and The Australian and New Zealand Bone and Mineral Society, aimed to evaluate analytical differences amongst commercial creatinine and phosphate assays, harmonize age-specific cut-offs and compare the ANZBMS TmP/GFR online calculator with existing products. A total of 11 360 results from The Royal College of Pathologists of Australasia Quality Assurance Programs were analyzed to assess creatinine and phosphate assay performance amongst five In Vitro Diagnostic (IVD) companies. Ortho-Clinical Diagnostics analyzers had a positive bias of up to 32% for serum phosphate and up to 29% for TmP/GFR. The other IVD companies produced comparable results and are suitable for harmonized reference intervals. To date, the AACB-ANZBMS TmP/GFR online calculator is the only validated Isotope Dilution Mass Spectrometry-creatinine aligned tool which caters for both pediatric and adult individuals, providing automatic interpretive comments to aid clinicians managing patients with hypophosphatemia.

Diagnostic Performance of Cystatin C in the Early Detection of Diabetic Kidney Disease at the University of Nigeria Teaching Hospital, Ituku-Ozalla.

There is an increase in the prevalence of diabetes mellitus (DM) globally. Individuals with diabetes mellitus are at higher risk of impairment of kidney function. This study evaluated the diagnostic performance of Cystatin C in the early detection of diabetic kidney disease (DKD). Across a sectional analytical study of 300 participants (200 study group and 100 control group). A relevant clinical history was obtained, and a physical examination was carried out. Venous blood was collected to assay for serum creatinine, serum albumin, serum cystatin C, serum urea, fasting blood glucose, and urine for the quantification of urine albumin excretion rate. The median age of the study group versus the control group was 62.50 for DM with proteinuria, 60.00 for DM without proteinuria, and 60.00 years for the control group (F = 3.524, p = 0.172). The laboratory parameters that were higher in the study group compared to the control group were FBG (141.0, 130, vs. 104 mg/dl, F = 68.456, p = <0.001), serum creatinine (109.0, 88.5, vs. 105.0 umol/l, F = 35.50, p = <0.001), serum cystatin C (1.24, 1.11, vs. 0.84 mg/L, F = 59.27, p = <0.001), and urine albumin excretion (230.0, 102.0, vs. 30.0 mg, F = 128.62, p = <0.001). The diagnostic performance of cystatin C using MDRD and cystatin C eGFR <60ml/min/1.73m2was 13% and 23%, respectively, for the study group without proteinuria. Also, when the diagnostic efficiency of the variables was compared using ROC, the AUC of creatinine eGFR (MDRD) was less than that of cystatin C eGFR between the cut-off levels of 30 mg and 300 mg of urine albumin excretion. Cystatin C eGFR had a strong negative correlation with urine albumin excretion when compared to creatinine eGFR (MDRD). This study showed the diagnostic performance of serum cystatin C in the early detection of DKD and that cystatin C-derived eGFR is more sensitive than serum creatinine-derived eGFR in detecting DKD early in people with DM.

A-048 Reference Interval and Clinical Performance Studies for Vitros® Immunodiagnostic Products Intact PTH II Assay to Aid in Diagnosis of Calcium and Parathyroid Disorders and Intraoperative Testing

Abstract Background Intact parathyroid hormone (iPTH) measurements aid in the differential diagnosis of hypercalcemia, hypocalcemia, and parathyroid disorders. The National Academy of Clinical Biochemistry has established guidelines for intraoperative PTH testing to monitor surgical success during parathyroidectomies. Studies were conducted to define the reference interval and clinical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay, using samples from healthy individuals and patients with conditions commonly requiring iPTH testing, including intraoperative cases. Methods The reference interval study was conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c in serum samples from 134 healthy individuals. For the clinical performance study, serum samples from individuals with hypoparathyroidism, primary hyperparathyroidism, chronic renal failure (secondary or tertiary hyperparathyroidism), hypercalcemia, hypercalcemia of malignancies, and hypocalcemia were tested. Intraoperative samples used were collected from parathyroidectomy patients in series at each surgical timepoint along with the standard plasma samples used to determine surgical success. Results The reference samples were composed of 134 serum donors that met all inclusion/exclusion criteria for healthy donors and had a normal test result on calcium, TSH, alkaline phosphatase, creatinine, and phosphate assays. The reference interval for iPTH was determined to be 14.2-75.2 pg/mL. The results in various disease states demonstrated the clinical performance of the Vitros iPTH II assay. Of 32 intraoperative sample series included in the study, three samples demonstrated no intraoperative decrease in iPTH due to surgical failures. Consistent with the goal of the parathyroidectomy procedure, at least a 50% decrease in iPTH was observed between the presurgical and post-excision samples in all other sample series. The clinical concordance with the Roche PTH assay used intraoperatively in these procedures was 100%. Conclusions Defining the reference interval for a normal healthy population and results from the intended use population demonstrated that the Vitros iPTH II assay can be used as an aid in the diagnosis of calcium and parathyroid disorders and intraoperative testing.

A-136 Icteric Interference is not Resolved with Sample Dilution in Serum Creatinine and Total Protein Assays

Abstract Background Icterus is a common endogenous interference that can cause falsely low results for serum creatinine and total protein. It can be defined by elevated unconjugated (indirect) and conjugated (direct) bilirubin levels and is most commonly associated with liver dysfunction. Recent literature suggests that dilutions can be a reliable method to reduce bilirubin interference. The purpose of this study was to determine whether the vendor’s on-board sample dilution can eliminate icteric interference with creatinine and total protein. Methods Creatinine (enzymatic) and total protein interference studies were performed on an automated chemistry analyzer (Roche Diagnostics, cobas c702). Low, mid, and high sample pools for each analyte were divided into four equal volumes. To achieve an icterus index (II) of approximately 40 (approximately 40 mg/dL of bilirubin), one sample pool was spiked with unconjugated bilirubin, and one pool was spiked with conjugated bilirubin. An equal amount of diluent was added into each control pool and remained at an II of approximately 0. The icteric and control samples were measured for conjugated and unconjugated bilirubin, serum indices, and the target analyte. Using the on-board dilution function, the icteric creatinine and total protein pools were diluted using a 1:4 and 1:3 dilution, respectively. All samples were analyzed in triplicate. Percent variance was found by calculating the difference between the average dilution result and control result and then dividing by the average control result. Results Conclusions Only modest alleviation of icteric interference was noted with dilution. The average bias was 10% for creatinine and 24% with total protein, after dilution. The on-board sample dilution is not effective in eliminating icteric interference when measuring both creatinine and total protein.

A-332 Identifying At-Risk Patients Pre-IV Contrast Administration via POCT Creatinine Measurement

Abstract Background The use of intravenous iodinated contrast in computerized tomography studies is associated with a small risk of acute kidney injury. Pre-existing chronic kidney disease is a recognized factor and assessment of renal function prior to contrast administration is essential. This study assessed the ability of the Abbott iSTAT creatinine assay to correctly identify IV-contrast patient risk using lab-based eGFR as the gold standard. Methods This was a retrospective study comparing POCT creatinine (whole blood, Abbott iSTAT enzymatic) and lab creatinine (plasma, Beckman Coulter AU5800 Jaffe) results on simultaneous samples collected in the emergency department. Anonymised data records were extracted from the laboratory database for 2020-2023. IV contrast risk was calculated using eGFR (CKD-EPI 2021) and classified as high risk (HR: eGFR &amp;lt; 30 mL/min/1.73 m2), moderate risk (MR: eGFR 30-59) and low risk (LR: eGFR &amp;gt;=60) as per the Royal Australian and New Zealand College of Radiologists 2018 guidelines, using the Beckman-based eGFR as the gold standard. Results 132 paired samples patients were available for analysis (61% male, average age 69 y (23-98), 70% Chinese, eGFR (iStat) 3-143, eGFR (Beckman) 3-121 mL/min/1.73 m2). The proportions of Beckman-based eGFR HR:MR:LR cases were 53:39:40. The prevalence of HR/MR cases was 70%. The diagnostic performance of the iSTAT-based eGFR to accurately identify HR/MR patients was: sensitivity 93.5%, specificity 95%, PPV 97.7%, NPV 86.4%, accuracy 93.9%. For different Beckman-derived eGFR categories, the mean difference in eGFR (iSTAT - Beckman), 95% lower limit of agreement (LOA) and upper LOA was: &amp;lt;30 mL/min/1.73 m2: -1.0, -3.2, -1.1; 30-60 mL/min/1.73 m2: 0.9, -13.3, 15.1; &amp;gt;60 mL/min/1.73 m2: 1.6, -16.8, 20.1. Linear regression fit (Passing-Bablok): CKD-EPI Beckman = 1.193 + 0.9773 CKD-EPI iSTAT. Correlation coefficient was 0.981. Kappa for the 3 categories of risk classification was 0.814. Conclusions The iSTAT creatinine assay could reliably identify patients at medium/high risk of acute kidney injury following intravenous contrast administration. Performance was best for low and high risk patients with 100% of high risk patients being correctly identified. It is a useful screening test but differences in eGFR of up to 20 mL/min/1.73 m2 may be seen between the Beckman and iSTAT eGFR values at higher levels, meaning numeric eGFR results are not interchangeable.

Evaluation of an At-Home Creatinine Assay for CKD Management: Pilot Method Comparison Study and Clinical Implications

Evaluation of an At-Home Creatinine Assay for CKD Management: Pilot Method Comparison Study and Clinical Implications

High-Performance Electrochemical Creatinine Sensors Based on β-Lead Dioxide/Single-Walled Carbon Nanotube Electrodes.

Creatinine is an important biomarker of kidney function and muscular metabolism. In this paper, we developed the β-lead dioxide/single-walled carbon nanotube (β-PbO2/CNT) and the β-PbO2/CNT ion-selective electrode (β-PbO2/CNT/ISE), which were used as highly sensitive potentiometric sensors for creatinine detection. The fabricated electrodes exhibited highly pH-sensitive characteristics due to the synergistic effect of the electrochemical properties of CNT and β-PbO2. Moreover, an ammonium-ion-selective membrane coating allowed the β-PbO2/CNT electrode to be NH4+-selective for direct detection of the ammonium ion. By exploiting the electrochemical characteristics of these electrodes, the creatinine assay was established through the one-step selective conversion of creatinine by creatinine deiminase, in which the OH- and NH4+ generated by the enzymatic reaction were detected using β-PbO2/CNT and β-PbO2/CNT/ISE electrodes as pH- and NH4+-responsive sensors, respectively. The total creatinine assay can be completed within ∼5 min. The assay results from β-PbO2/CNT and β-PbO2/CNT/ISE showed excellent sensitivity values of -75.56 and 64.62 mV in the detection range of 10-400 μM with a fast response (20 s), and the limits of detection were calculated to be 0.06 and 0.13 μM, respectively. Moreover, the developed creatinine sensor showed high selectivity against 11 interfering bio/chemical species with negligible interferences (selectivity coefficient <10-4) and excellent repeatability (>97% within 25 cycles) and long-term stability for 4 weeks of storage. In addition, the feasibility and practicality of the device were successfully demonstrated in human serum tests, with recoveries of 95-104% for PbO2/CNT and 92-110% for PbO2/CNT/ISE.

Assessment of the toxic influence of locally formulated pesticides on hepatic and renal biomarkers in male Wistar rats.

There is growing concern of the potential damage to vital organs after long term exposure to locally formulated pesticides in rural area of Nigeria. This study was designed to assessed the effects of the individual chemical compound and their combination on the kidney and liver of rats' model. Fifty-four rats divided into six groups and three sub-groups were exposed to 25, 50 and 75% dose of each of the pesticide's LD50 for 4h at 3days interval in an inhalation chamber for 28days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TOT_BIL), creatinine and urea assay showed significant increase at the aforementioned doses in comparison to the control group. The red blood cell counts, hematocrit and hemoglobin concentrations were significantly altered in the rats administered varying doses of the pesticides when compared with the control. Similar result was obtained for the differential white blood cell counts. Histopathological examinations of the liver tissue of rats showed infiltrated sinusoids, traces of karypyknosis, vacuolar degeneration and microvesicular steatosis while that of the renal tissue showed glomeruli atrophy leading to widened Bowman's spaces as well as few shrunken glomeruli and varied level of degenerative tubular changes to tubular necrosis. This study established that individual pesticides and their mixture is toxic to the liver and kidney, as evidenced by the elevated markers of renal and liver functions and distortion of the structure of both organs as revealed by their photomicrographs. Therefore, it is a matter of public health significance to regularly monitor pesticide residues in foods and humans in order to assess the food safety risk and population exposure to pesticides.

Acute Kidney Injury Among Asphyxiated Neonates In Sokoto, North West Nigeria

Background: Birth asphyxia and its attendant complications remain a common problem in our neonatal intensive care units. Compelling evidence from various epidemiologic studies shows that Acute Kidney Injury (AKI) is indeed one of the commonest complications of birth asphyxia. The kidneys are sensitive to oxygen deprivation, renal insult may occur within few hours of hypoxic-ischemic episode, which if prolonged could lead to irreversible cortical and or tubular necrosis. Aim: To determine the prevalence and factors associated with AKI among asphyxiated term neonates in Usmanu Danfodiyo University Teaching Hospital (UDUTH) Sokoto, Nigeria Materials and methods: One hundred and nineteen asphyxiated term neonates admitted into the special care baby unit of UDUTH Sokoto participated in the study. Birth asphyxia was defined as failure to initiate and sustain breathing at birth with Apgar scores ≤ 5 at 5 minutes in the presence of arterial cord blood pH &lt; 7 and base deficit &gt;12mmol. Blood samples were taken for arterial blood gas analysis within one hour of life. Moderately and severely asphyxiated neonates who satisfied the inclusion criteria were consecutively recruited into the study and serum creatinine assay was done on day 3 and day 5 of life. AKI was defined as a rise in serum creatinine ≥ 0.3mg/dl over 48 hours. Quantitative variables such as birth weight, length, occipitofrontal circumference (OFC) were expressed using mean, standard deviation and range, while qualitative variables like gender, mode of delivery and grade of asphyxia were summarised using frequency and percentages. Chisquare and fisher’s exact tests were applied to determine if any relationship exists between sociodemographic/clinical factors and AKI. A p-value of &lt; 0.05 was considered statistically significant. Results: Of the 119 asphyxiated term neonates 74 (62.2%) were males while 45 (37.8%) were females giving a M:F ratio of 1.6:1. Majority 96 (80.7%) of the subjects had normal birth weight with a mean birth weight of 3.1 ± 0.6kg. The mean gestational age recorded was 38.2 ± 1.1 months The prevalence of AKI in the study subjects was 42.9%. The grade of birth asphyxia was significantly associated with AKI with a prevalence odds ratio of 7.2 (95CI 2.8-18). Conclusion: The prevalence of AKI in asphyxiated term neonates in UDUTH Sokoto was high and the grade of birth asphyxia was found to be significantly associated with AKI

Tuning of fluorescence in titanium carbide MXene nanosheets with La3+ ion doping for the recognition of creatinine biomarker in biofluids

There is a strong correlation between the concentration of creatinine in human urine and the overall health of the kidneys. Therefore, there has been a persistent need for a rapid, and cost-effective quantitative method to assay creatinine levels in urine. Herein, green fluorescent La3+ doped titanium carbide nanosheets (La3+-doped Ti3C2 NSs) are fabricated via HF etching method by using Ti3AlC2 as MAX phase material and La(NO3)3 as a doping agent. As synthesized fluorescent La3+-doped Ti3C2 NSs are stable, showing green fluorescence under UV light. The as-synthesized La3+-doped Ti3C2 NSs act as a fluorescent sensor for the sensitive recognition of creatinine biomarker. The La3+-doped Ti3C2 NSs-based fluorescence method showed a fluorescence quenching at emission wavelength 518 nm towards creatinine with a linear range of 0.25–7.5 μM and detection limit of 63.44 nM. The paper strip based on La3+-doped Ti3C2 NSs was developed for the visual identification of creatinine. Furthermore, La3+-doped Ti3C2 NSs were used as probes for imaging of Saccharomyces cerevisiae cells. Also, the as-fabricated La3+-doped Ti3C2 NSs propose a quick response giving a cost-effective analytical strategy for the selective assay of creatinine in biofluids (plasma and urine).

Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.

This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).

Antitumor effect of Iso-mukaadial acetate on MCF-7 breast cancer mice xenograft model

Antitumor drugs used today have shown significant efficacy and are derived from natural products such as plants. Iso-mukaadial acetate (IMA) has previously been shown to possess anticancer properties by inducing apoptosis. The purpose of this study was to investigate the therapeutic effect of IMA in the breast cancer xenograft mice model. Female athymic nude mice were used and inoculated with breast cancer cells subcutaneously. Untreated group one served as a negative control and positive control group two (cisplatin) was administered intravenously. IMA was administered orally to group three (100 mg/kg) and group four (300 mg/kg). Blood was collected (70 μL) from the tail vein on day zero, day one and day three. Tumor regression was measured every second day and body mass was recorded each day. Estimation of serum parameters for renal indices was examined using a creatinine assay. Histopathological analysis was conducted to evaluate morphological changes of liver, kidney, and spleen tissues before and after compound administration under a fluorescence light microscope. Histopathological analysis of tumors was conducted before and after compound administration. Apoptotic analysis using the TUNEL system was conducted on liver, kidney, and spleen tissues. Tumor shrinkage and reduction in body mass were observed after treatment with IMA. Serum creatinine was slightly elevated after treatment with IMA at a dosage of 100 and 300 mg/kg. Histopathological results of the liver exhibited no changes before and after IMA while the kidney and spleen tissues showed changes in the cellular structure. IMA showed no cytotoxic effect on the tumor cells, and cell proliferation was observed. Apoptotic assay stain with TUNEL showed apoptotic cells in spleen tissue and kidney but no apoptotic cells were observed in liver tissue section treated with IMA. IMA showed clinical toxic signs that resulted in the suffering and death of the mice immediately after IMA administration. Histopathology of tumor cells showed that IMA did not inhibit cell proliferation and no cellular damage was observed. Therefore, based on the results obtained, we cannot make any definitive conclusion on the complete effect of IMA in vivo. IMA is toxic, poorly soluble, and not safe to use in animal studies. The objective of the study was not achieved, and the hypothesis was rejected.

Dopamine infusion at typical infusion rates does not cause interference on plasma creatinine assays

a) ObjectivesDopamine is known to cause negative interference on enzymatic creatinine measurement. However, its effect on the Jaffe reaction, and its concentration required to interfere with enzymatic reactions, remain uncertain. This study was designed to study the interference of stable dopamine infusion on Jaffe and enzymatic creatinine assays, as well as the effect of dopamine infusion drip arm contamination on both creatinine assays. b) Design and MethodsFor the first part of the study, dopamine was spiked into pooled plasma samples at different concentrations to mimic the scenario of patients on dopamine infusion at an infusion rate between 2 and 20 μg/kg/min. For the second part, dopamine preparation of 2 g/L (same as the preparation used clinically) was mixed with pooled plasma samples at different proportions to mimic drip arm contamination. Creatinine concentrations were measured using Jaffe and enzymatic reactions. c) ResultsThe first part showed that creatinine measurements were not interfered by dopamine infusion at an infusion rate between 2 and 20 μg/kg/min. The second part showed that dopamine could negatively interfere with enzymatic creatinine assays, even with minute drip arm contamination. The effect on the Jaffe reaction was less significant. d) DiscussionCreatinine concentration could be reliably measured by Jaffe or enzymatic reactions if samples are from venous access sites other than the site of dopamine infusion. When dopamine interference on enzymatic creatinine assays is suspected, using the Jaffe reaction to cross-check may provide additional useful information.

Comparative study between three creatinine assay methods: What is the impact on GFR estimation by CKD-EPI?

Comparative study between three creatinine assay methods: What is the impact on GFR estimation by CKD-EPI?

Understanding the limitations of your assay using EQA data with serum creatinine as an example.

Laboratories need to take into consideration the specificity and imprecision of assays not only in verification, but also of quality assessment. This study investigates the composition of serum used in EQA materials by comparing material from a single and multiple donors (pooled material), across multiple methods, using creatinine as an example. Sixteen different serum matrices were distributed as 36 specimens through the UK NEQAS for Acute and Chronic Kidney Disease Scheme from March 2022 to March 2023. Male-only and female-only serum was used as single donations, pooled donations, unmanipulated or with addedexogenous creatinine. Specimens were distributed to primarily UK participants (approximately n=500) for creatinine analysis. Data has been reviewed by method compared to the enzymatic creatinine method principle mean. From the 16 different matrices, only the enzymatic creatinine assay systems from Roche Cobas and Siemens Atellica met the minimum acceptable bias goal, from biological data, of 5.6 %, in all specimens. Pooled material showed less variation in bias across all methods. Since Laboratories invest a lot of time and money in quality management, they need to know the limitations of their assays so that they are not investigating 'apparent' EQA/IQC problems which are purely due to non-specific, imprecise assay, rather than an analytical issuein their laboratory. When large numbers of individual donations are combined, interferents are essentially diluted out. Therefore, if EQA material is of this type it will be very difficult to determine the actual assay's bias and variability.

Study of the antitumor activity of the combination baicalin and epigallocatechin gallate in a murine model of vincristine-resistant breast cancer

Background: Breast cancer is one of the primary causes of death in women worldwide. Yearly, a quarter of cancer cases in women are breast cancer. The problem is aggravated by the emergence of chemotherapeutic resistance. One of the practices to overcome this problem is using natural products along with chemotherapy. Epigallocatechin Gallate (EGCG) is the main efficient catechin in green tea. Baicalin is the main active chemical constituent of Scutellaria baicalensis. Both natural products have anti-cancer and improving resistance activities. Therefore, a combination of EGCG and baicalin may afford a possible way out to overcome chemotherapeutic resistance. Methods: EGCG and baicalin were tested on Vincristine-sensitive (EMT-6/P) and Vincristine-resistant (EMT-6/V) mouse mammary cell lines. Antiproliferative and apoptotic effects were assessed for EGCG, baicalin, their combination, and Vincristine in vitro using MTT and caspase-3 assays. An in vivo study was conducted to assess the effect of EGCG, baicalin, their combination, vincristine, vincristine along with the combination in both EMT-6/P and EMT-6/V mouse mammary cell lines. The safety profile was also considered using liver enzymes and creatinine assays. Results: in vitro, EGCG and baicalin had synergistic effects in both cell lines. The combination of baicalin and EGCG as 140 and 100 µM respectively, caused an apoptotic effect higher than the single treatment of baicalin 175 µM or EGCG 125 µM, in vincristine-resistant cell lines. In vivo, the combination along with vincristine significantly enhanced the reduction of tumour size in mice implanted with EMT-6/P and EMT-6/V cell lines. According to the safety profile, the combinations of EGCG and baicalin are safe. Conclusion: The combination of baicalin and EGCG can be optimistic in improving vincristine-resistant cells to treatments.

Targeting cisplatin resistance in breast cancer using a combination of Thymoquinone and Silymarin: an in vitro and in vivo study

Background: Breast cancer (BC) is considered the most diagnosed cancer among women globally. This is because of its high possibility of metastasis and high resistance to chemotherapy. Cisplatin is a platinum-based antitumor agent that is used to treat various types of cancer. However, the main obstacle to using this drug is drug resistance. Drug resistance is a cause of most relapses of cancer which eventually lead to death. Nowadays, combining natural products is a trend to overcome drug resistance. Thymoquinone (TQ) is a natural phytochemical that exists mainly in blackseed. It has been used in medicine for decades, especially as an anticancer agent. Silymarin is a milk thistle compound that exhibits anticancer, hepatoprotective, and neuroprotective activity. Hence, the combination of TQ and silymarin could be a probable solution to treat cancer and reduce chemoresistance. Methods: This study tested this combination on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. Apoptotic and antiproliferative activity was assessed for TQ and silymarin in vitro using caspase-3 and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays, respectively. An in vivo study was performed to evaluate the effect of TQ and silymarin combination in mice inoculated with EMT6/P and EMT6/CPR cells. The safety profile was also examined using creatinine and liver enzyme assays. Results: In vitro, the TQ and silymarin combination synergized in both cell lines. Also, this combination caused apoptosis induction at a higher rate than the single treatment in both cell lines. In vivo, TQ and silymarin combination resulted in a remarkable reduction in tumor size and enhanced the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. According to the safety profile results, TQ and silymarin combination was safe. Conclusion: In conclusion, the combination of TQ and silymarin provides a promising solution in treating BC resistant to cisplatin by inducing apoptosis. Further studies are needed to define the exact anticancer mechanisms of this combination.