Urinary Creatine Research Articles

Raman Spectroscopic Analysis of Urinary Creatine and Phosphate in Athletes: Pre- and Post-Training Assessment.

The aim of this study was to detect biochemical components in the urine of bodybuilders who ingested creatine pretraining compared to individuals who did not ingest creatine after physical exercise using Raman spectroscopy. Twenty volunteers practicing bodybuilding were selected to collect pre- and post-training urine samples, where 10 volunteers ingested creatine 30 min before pretraining urine collection (creatine group), and 10 did not (control group). The samples were subjected to Raman spectroscopy, and the spectra of both creatine and control groups and the difference (post-pre) for both groups were analyzed. Principal component analysis (PCA) technique was applied to the samples. The results showed peaks of creatine and phosphate in urine after training (creatine post-training group), suggesting that part of the creatine was absorbed and metabolized, and part was excreted. Raman spectroscopy could be applied to detect biocompounds in urine, such as unmetabolized creatine and phosphate.

Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers.

Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT). Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified using liquid chromatography-mass spectrometry to determine if nonsmoker cases can be distinguished from sex and age-matched controls in comparison with tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening. Urinary levels of CR and NANA were significantly higher and comparable in nonsmokers and tobacco smoker cases than population controls in both cohorts. Receiver operating characteristic analysis for combined CR and NANA levels in nonsmokers of the exploratory cohort resulted in better predictive performance with the AUC of 0.94, whereas the validation cohort nonsmokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in nonsmokers as well as tobacco smoker cases in both cohorts. Measuring CR and NANA in urine liquid biopsies could identify nonsmokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers.

Analysis of differences in early detection of chronic kidney disease with urine creatinine, proteins and individual health status based on behavioural, stress and genetic factors in Kendari City, Indonesia

Background:Early detection of chronic kidney disease needs to be developed because the prevalence of chronic kidney disease continues to increase in Kendari City, Indonesia. Objective:The study aimed to analyse of differences in early detection of chronic kidney disease with urine proteins, creatinine, and individual health status based on behaviours, psychological-stress environment and genetic factors in Kendari City, Indonesia. Methods:This research used quantitative method with a cross sectional study approach. This study was conducted in Kendari City, Southeast Sulawesi, Indonesia, which recruited 136 subjects aged between 24-70 years. The participants were interviewed and tested urine. The dependent variables are protein-urine, creatinine, and health status. The independent variables are behaviours, psychological environment-stress and genetics. Data analysis used multinomial logistic regression statistical tests. Results: This study suggests that there are differences between tests for urine protein levels, creatinine and individual health status for early detection of chronic kidney disease which is associated with behaviours, psychological-stress environment and genetic factors in Kendari City. Protein-urine can be used early detection of chronic kidney disease which is related to daily water consumption (p=0.001, OR=1.56), calory intake (p=0.036, OR=2.13) and psychological stress environment (p=0.017, OR=0.11). However, urine creatine test cannot be use for early detection of chronic kidney disease. Meanwhile, individual’s health status can be used to early detection of chronic kidney disease with relating to daily water consumption behaviour of less than 1000 ml a day (p<0.0001, OR=1.56), physical activity (p<0.05, OR=5.7), medication adherence (P<0.01, OR=0.4), and psychological stress environment (p<0.0001, OR=8.6). Conclusion: Early detection of chronic kidney disease may be more effective by observing health status directly, or by urine protein testing, compared to urine creatinine testing. Keywords:Chronic kidney disease, behaviour, genetic, stress, proteins.

Spectrophotometric and chromatographic analysis of creatine:creatinine crystals in urine

Creatinine is the end product of the catabolism of creatine and creatine phosphate. Creatine phosphate serves as a reservoir of high-energy phosphate, especially in skeletal and cardiac muscle. Besides typical known changes in serum and urinary creatinine concentrations, rare cases associated with changes in serum and urinary creatine levels have been described in the literature in humans. These cases are mostly linked to an excessive intake of creatine ethyl ester or creatine monohydrate, often resulting in increased urine creatinine concentrations. In addition, it is known that at such elevated creatinine concentrations, creatinine crystallisation may occur in the urine. Analysis of crystals and urinary concrements, often of heterogenous chemical composition, may provide diagnostic and therapeutic hints to the benefit of the patient. The aim of the present work was to analyze urine crystals of unclear composition with microscopic and spectroscopic techniques.On routine microscopic analysis of urine, a preliminary suspicion of uric acid or creatinine crystals was expressed. The crystals were of a cuboid shape and showed polarization effects in microscopy. The dried urine sample was whitish-orange in colour, odourless and dissolved well in water. Protein concentration in dry weight (DW) urine was about 0.3 mg/mg. The measured zinc content in the studied sample was approximately 660 µg/g DW sample and copper content was approximately 64 µg/g DW sample. A lead signal of around 10 µg/g DW sample was also observed. UV–Vis analysis showed a maximum creatine peak around 220 nm, compatible with the spectrum of creatinine with a maximum peak of 230 nm. Using HPLC technique, an extreme high ratio of creatine to creatinine of about 38 was measured, which led to the conclusion of the occurrence of rare creatine crystals in urine.

Do large parathyroid adenomas increase the risk of severe hypercalcemia?

<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0–3.5 g are called “large” or “giant” adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm<sup>3</sup> (control group). In both groups, the majority were women (81.5% – study group, 90.5% – control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3–0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>

Long-term efficacy and safety of baricitinib in patients with severealopecia areata: 104-week results from BRAVE-AA1 and BRAVE-AA2.

Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA. To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.

Rapid and Direct Detection of Trimethylamine N-oxide Using an Off-Chip Capacitance Biosensor with Readout SoC for Early-Stage Thrombosis and Cardiovascular Disease.

A demonstration of an off-chip capacitance array sensor with a limit of detection of 1 μM trimethylamine N-oxide (TMAO) to diagnose a chronic metabolism disease in urine is presented. The improved Cole-Cole model is employed to determine the parameters of R_catalyzed, C_catalyzed, and Rp_catalyzed, enabling the prediction of the catalytic resistance of enzyme, reduction effects of the analyte, and characterize the small signal alternating current properties of ionic strength caused by catalysis. Based on the standard solutions, we investigate the effects of pixel geometry parameters, driving electrode width, and sensing electrode width on the electrical field change of the off-chip capacitance sensor; the proposed off-chip sensor with readout system-on-chip exhibits a high sensitivity of 21 analog-to-digital converter counts/μM TMAO (or 2.5 mV/μM TMAO), response time of 1 s, repetition of 98.9%, and drift over time of 0.5 mV. The proposed off-chip sensor effectively discriminates TMAO in a phosphate-buffered saline solution based on minute changes in capacitance induced by the TorA enzyme, resulting in a discernible 2.15% distinction. These measurements have been successfully corroborated using the conventional cyclic voltammetry method, demonstrating a mere 0.024% variance. The off-chip sensor is crafted with a specific focus on detecting TMAO, achieved by excluding any reduction reactions between the TMAO-specific enzyme TorA and the compounds creatine and creatinine present in urine. This deliberate omission ensures that the sensor's attention remains solely on TMAO, thereby enhancing its precision in achieving accurate and reliable TMAO detection.

Altered dietary behaviour during pregnancy impacts systemic metabolic phenotypes.

Evidence suggests consumption of a Mediterranean diet (MD) can positively impact both maternal and offspring health, potentially mediated by a beneficial effect on inflammatory pathways. We aimed to apply metabolic profiling of serum and urine samples to assess differences between women who were stratified into high and low alignment to a MD throughout pregnancy and investigate the relationship of the diet to inflammatory markers. From the ORIGINS cohort, 51 pregnant women were stratified for persistent high and low alignment to a MD, based on validated MD questionnaires. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the urine and serum metabolite profiles of these women at 36 weeks of pregnancy. The relationship between diet, metabolite profile and inflammatory status was investigated. There were clear differences in both the food choice and metabolic profiles of women who self-reported concordance to a high (HMDA) and low (LMDA) Mediterranean diet, indicating that alignment with the MD was associated with a specific metabolic phenotype during pregnancy. Reduced meat intake and higher vegetable intake in the HMDA group was supported by increased levels of urinary hippurate (p = 0.044) and lower creatine (p = 0.047) levels. Serum concentrations of the NMR spectroscopic inflammatory biomarkers GlycA (p = 0.020) and GlycB (p = 0.016) were significantly lower in the HDMA group and were negatively associated with serum acetate, histidine and isoleucine (p < 0.05) suggesting a greater level of plant-based nutrients in the diet. Serum branched chain and aromatic amino acids were positively associated with the HMDA group while both urinary and serum creatine, urine creatinine and dimethylamine were positively associated with the LMDA group. Metabolic phenotypes of pregnant women who had a high alignment with the MD were significantly different from pregnant women who had a poor alignment with the MD. The metabolite profiles aligned with reported food intake. Differences were most significant biomarkers of systemic inflammation and selected gut-microbial metabolites. This research expands our understanding of the mechanisms driving health outcomes during the perinatal period and provides additional biomarkers for investigation in pregnant women to assess potential health risks.

SAT569 Papillary Thyroid Carcinoma With Renal Metastasis Treated With Radioactive Iodine: A Case Report

Abstract Disclosure: A.A. Apa-ap: None. M.B. Sedurante: None. J. Lacuata: None. J. Gacula: None. V. Lee: None. M.L. Hernandez: None. INTRODUCTION. Papillary thyroid cancer (PTC) is one of the most treatable cancers in comparison to undifferentiated thyroid malignancies. It advances slowly, and there is only 1-4 percent of cases of distant metastases. Renal involvement from PTC is very rare with an incidence of 0.47 percent. CASE DESCRIPTION. This paper describes a 34-year-old Filipino female presenting with an 8-year history of hoarseness and a gradually enlarging anterior neck mass. Metastatic workup revealed innumerable bilateral pulmonary nodules bilateral cervical lymphadenopathy, and bilateral renal mass on CT scan. The right pole of the kidney shows a solid heterogeneously enhancing partially-exophytic focus measuring 4.9 x 4.2 x 4.3cm likely a primary renal cell carcinoma versus metastasis. The left renal mass shows a hypodense non-enhancing partially-exophytic focus measuring 3.9 x 3.6 x 3.6cm probably a renal cyst. Clinically, the patient did not show any urinary symptoms and creatine clearance was normal. The patient underwent total thyroidectomy and neck dissection and histopathology revealed PTC. The patient underwent simultaneous ultrasound right renal mass biopsy which revealed few fragments of thyroid tissues with atypia most likely representative of metastasis of PTC. Since the radiographic finding was suggestive of a renal cyst, the left renal mass was not biopsied. Patient refused nephrectomy and underwent 1 cycle of Radioactive Iodine (RAI) Therapy. Post therapy whole body scan showed mildly increased and diffuse tracer uptake activity in bilateral lungs and large avid focus, approximately 5.0 x 4.4 cm, seen in the inferior pole of the right kidney. Surveillance showed increased thyroglobulin. To date, the patient still refused surgery and is contemplating undergoing another cycle of RAI therapy. DISCUSSION. Due to the rarity of the metastatic site, the ideal course of treatment for this illness is unknown. To our knowledge, there are only approximate of 30 case reports on WDTC with renal metastasis in the literature. Presentation: Saturday, June 17, 2023

Reference Intervals of Serum Iodine Concentration in Chinese Pregnant Women.

The study aims to establish trimester-specific reference ranges for serum iodine (SI) in Chinese pregnant women and explore its associations with maternal and infantile thyroid function. Apparently healthy pregnant women were enrolled during their first antenatal visit. Fasting venous and spot urine samples were collected for determining serum and urinary iodine (UI) levels by a validated inductively coupled plasma mass spectrometry. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), and neonatal TSH levels were tested by electro-chemiluminescent assay. The reference ranges of SI were established by percentile method and reported as 2.5-97.5%. ROC analysis was applied to compare the discriminative ability of SI, UI, and UI to urinary creatine ratio (UI /UCr) in early pregnancy for various thyroid conditions. The trimester-specific reference ranges of SI for Chinese pregnant women were 60.91-114.53 μg/L for the first trimester (T1, n = 1029), 54.57-103.42 μg/L for the second trimester (T2, n = 379), and 52.03-110.40 μg/L for the third trimester (T3, n = 455). Maternal SI at T1 but not UI and UI/UCr was significantly correlated with FT3 (r = 0.393, P < 0.001), FT4 (r = 0.637, P < 0.001), and TSH (r = -0.299, P<0.001). Maternal SI change% from T1 to T2 (but not SI change% from T1 to T3) had marginal correlation with neonatal TSH (r=-0.106, P=0.046). ROC analysis showed that maternal SI at T1 had better predictability for several thyroid conditions than UIC and UI/UCr.

Cystic Parathyroid Adenomas as a Risk Factor for Severe Hypercalcemia.

(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.

Estimation of skeletal muscle mass in 4-year-old children using the D3-creatine dilution method

BackgroundGiven limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh.MethodsFollowing D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2–4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography–tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer.ResultsSMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: −0.031, 0.038; n = 91).ConclusionsThe D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach.ImpactThe D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants.SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength.High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Abstract 1001: Urinary metabolite diagnostic and prognostic liquid biopsy biomarkers of lung cancer - never smokers versus tobacco smokers

Abstract Introduction: Never smokers account for 10-13% of all lung cancer cases in the United States. The etiology is attributed to multiple causes including exposure to passive smoking, parental smoking, asbestos and radon. However, these lung cancer cases do not fit the current United States Government-funded criterion of low-dose computed tomography that identifies early stages of lung cancer with higher survival following surgical removal. Methods: The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified by liquid chromatography-mass spectrometry to determine if never smokers with non-small cell lung cancer (NSCLC) can also be identified alongside tobacco smoker NSCLC cases as compared with gender and age-matched non-cancer population controls. Results: These cancer biomarkers were significantly higher and comparable in never-smokers and tobacco smokers cases compared to population controls. Receiver Operating Characteristics (ROC) analysis in never smokers was equivalent for CR and NANA levels area under the curve (AUC) 0.91. In contrast, combined CR and NANA levels resulted in better predictive performance (AUC 0.94). Kaplan-Meier survival curves showed that high levels of CR and NANA were associated (p&amp;lt;0.05) with increased cancer-specific death in never-smokers and tobacco smokers. Therefore these metabolites are independent of Tobacco smoking. NANA metabolite category factor, histology and stage were independent predictors of survival (p&amp;lt;0.05) in multivariate analyses for never smokers as shown in Table 1. Conclusions: These results indicate that measuring CR and NANA in liquid biopsy urine could identify never-smoking lung cancer candidates for LDCT screening and warrant prospective studies of these biomarkers in high-risk environments. Table 1. Univariate and multivariate regression analysis for factors associated with survival in the never smokers population Univariate Analysis Multivariate analysis Factors Levels N HR 95%CI P-value HR 95%CI P-value Stage Early Stage (I &amp; II); Late Stage (III &amp; IV) 145 3.52 2.3, 5.3 &amp;lt;0.001 3.94 2.2, 6.8 &amp;lt;0.001 Histology Adenocarcinoma; Squamous cell carcinoma 114 1.62 0.7, 3.5 0.26 3.42 1.4, 7.9 0.01 CR Category Low; High 166 1.34 0.8-2.1 0.19 1.67 0.9, 3.0 0.08 NANA Category Low; High 166 2.11 1.1-3.9 0.009 2.31 1.0, 5.0 0.02 Age N=166 166 1.00 0.9, 1.0 0.50 0.99 0.9, 1.0 0.4 Sex Male; Female 166 0.87 0.5, 1.2 0.49 0.90 0.5, 1.5 0.7 Race African American; European American 166 0.82 0.2, 2.5 0.75 0.40 0.1, 1.3 0.2 Citation Format: Bhavik Dalal, Takeshi Tada, Daxesh P. Patel, Mohammed Khan, Takahiro Oike, Yasuyuki Kanke, Amelia Parker, Majda Haznadar, Leila Toulabi, Kristopher Krausz, Ana Robles, Elise Bowman, Frank Gonzalez, Curtis Harris. Urinary metabolite diagnostic and prognostic liquid biopsy biomarkers of lung cancer - never smokers versus tobacco smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1001.

Handgrip Strength Is Positively Associated with 24-hour Urine Creatine Concentration

Muscle mass evaluation methods are often expensive and therefore limited in their daily use in clinical practice. In this study, we investigated the relationship between hand grip strength (HGS) and other parameters of body measurements with urine creatinine, especially to investigate whether HGS measurement is an indicator of muscle metabolism. In total, 310 relatively healthy people (mean age 47.8 + 9.6; 161 people or 51.9% of the total population were men) who were undergoing preventive examinations were included in this study and given a container to collect 24-h urine, and the amount of creatinine in the urine was determined by a kinetic test without deproteinization according to the Jaffe method. A digital dynamometer (Takei Hand Grip Dynamometer, Japan) was used in the measurement of HGS. There was a significant difference in 24-h urine creatinine (24 hCER) between the sexes, with a mean of 1382.9 mg/24 h in men and 960.3 mg/24 h in women. According to the correlation analysis, the amount of urine creatinine was related to age (r = -0.307, p < 0.001 in men, r = -0.309, p < 0.001 in women), and HGS (r = 0.207, p = 0.011 in men, r = 0.273, p = 0.002 in women) was significant for either sex. However, other parameters of body measurements, such as girth, forearm circumference, and muscle mass measured by bioelectrical impedance, were not related to urine 24 hCER. A correlation between HGS and 24 hCER was observed in age groups. We found that HGS is a potential marker in muscle metabolism assessment that is proven through 24 hCER. In addition, therefore, we suggest using the HGS measure in clinical practice to evaluate muscle function and well-being.

The Relationship between Metabolic Control Status and Microalbuminuria in Pediatric Diabetes Mellitus Patients at Dr. M. Djamil General Hospital, Padang, Indonesia

Background: Diabetes mellitus (DM) is a complex metabolic disorder that can cause many complications. HbA1c measurement can help monitor long-term serum glucose regulation. Microalbuminuria in DM patients is a risk factor for these complications, so evaluation of risk factors for prevention is necessary. This study aimed to determine the relationship between metabolic control status and microalbuminuria in pediatric diabetes mellitus patients at Dr. M. Djamil General Hospital, Padang, Indonesia.&#x0D; Methods: This study is an analytic observational study with a cross-sectional approach. A total of 34 children with DM aged 1-18 years participated in this study. Sampling was carried out using the consecutive sampling method at the pediatric polyclinic of Dr. M. Djamil General Hospital, Padang, Indonesia, from November 2021-April 2022. Metabolic control status was assessed by measuring HbA1C levels and microalbuminuria by measuring the urine albumin-creatinine ratio. Data analysis used the Chi-square test, with a p-value &lt;0.05.&#x0D; Results: The average respondent was 13.2 ± 3.3 years old with a duration of suffering from DM 2.5 ± 2 years. Most of the respondents were male (52.9%), suffered from type 1 DM (94.1%), had uncontrolled metabolic control status (82.3%), had a normal creatine albumin ratio (82.4%), never had diabetic ketoacidosis (79.4%), had no family history of DM (85.3%) and had normal blood pressure (94.1%). It is known that the average urea and creatinine are within normal limits. The average HbA1c value is 11.9 ± 3.39%. The median urine creatine albumin ratio was 7.98 (0-255.74) ug/mg. Microalbuminuria in uncontrolled metabolic control status was found in as much as 17.6%, whereas in controlled metabolic control status, no microalbuminuria was found. Statistically, there is no significant relationship (p&gt;0.05).&#x0D; Conclusion: There is no relationship between metabolic control status and microalbuminuria in pediatric diabetes mellitus patients at Dr. M. Djamil General Hospital, Padang, Indonesia.

1H NMR-based metabolomics of paired tissue, serum and urine samples reveals an optimized panel of biofluids metabolic biomarkers for esophageal cancer.

The goal of this study was to establish an optimized metabolic panel by combining serum and urine biomarkers that could reflect the malignancy of cancer tissues to improve the non-invasive diagnosis of esophageal squamous cell cancer (ESCC). Urine and serum specimens representing the healthy and ESCC individuals, together with the paralleled ESCC cancer tissues and corresponding distant non-cancerous tissues were investigated in this study using the high-resolution 600 MHz 1H-NMR technique. We identified distinct 1H NMR-based serum and urine metabolic signatures respectively, which were linked to the metabolic profiles of esophageal-cancerous tissues. Creatine and glycine in both serum and urine were selected as the optimal biofluids biomarker panel for ESCC detection, as they were the overlapping discriminative metabolites across serum, urine and cancer tissues in ESCC patients. Also, the were the major metabolites involved in the perturbation of "glycine, serine, and threonine metabolism", the significant pathway alteration associated with ESCC progression. Then a visual predictive nomogram was constructed by combining creatine and glycine in both serum and urine, which exhibited superior diagnostic efficiency (with an AUC of 0.930) than any diagnostic model constructed by a single urine or serum metabolic biomarkers. Overall, this study highlighted that NMR-based biofluids metabolomics fingerprinting, as a non-invasive predictor, has the potential utility for ESCC detection. Further studies based on a lager number size and in combination with other omics or molecular biological approaches are needed to validate the metabolic pathway disturbances in ESCC patients.

P8.030: Post-kidney Transplant Prospective Comparison of Measured Urinary Creatinine Clearance With Estimated -eGFR Based on Serum Creatinine or Kinetic- KeGFR for Rapid Changes in Serum Creatinine

Introduction: Post kidney transplant (KTx) with functioning renal allograft, serum creatinine continues to decrease at a variable rate until it stabilizes. Currently, the Cockcroft- Gault (C-G) and Modification of Diet in Renal Disease MDRD-4 formulae, and are based on a single serum creatinine value to estimate GFR for chronic kidney disease. For rapid changes in serum creatinine, the kinetic estimated GFR (KeGFR)1 formula was developed for recovering acute kidney injury. However, post-KTx with functioning allograft eGFR and KeGFR formulae/calculators’ values are not compared with measured urinary creatinine clearance by any glomerular isotope excretion methods. Hence, the medications requiring dose adjustment based on renal function might not be adjusted appropriately. The aim of the present study is to compare actual urinary creatinine clearance every 12 hours with C-G, MDRD-4, and (KeGFR) after functional KTx. Patient and method: 34 consenting subjects (mean age 55.2 +/- 13.8 years; 14 male) were enrolled of which 24 had immediate primary allograft function. These were prospectively studied under IRB-approved protocol. Urine was collected every 12 hours through a Foley catheter post-KTx until serum creatinine was stabilized. Creatinine clearance was calculated {U (urinary creatinine) x V (urinary volume)/ S (serum creatinine); (UV/S)}. Over 200 creatinine clearance values were compared with C-G, MDRD-4, and Chen’s KeGFR calculator at 12, 24- and 48-hours intervals. Results: At each time point, the measured urinary creatinine clearance was consistently higher compared with eGFR by C-G, MDRD-4 formula, and KeGFR by Chen calculator1 until serum creatinine was stabilized around 2mg/dL (Figure-1). The mean creatinine clearance was 68.1 ± 22.1 mL/min. Twenty-two (91%) subjects had a >50% decrease in serum creatinine at the time of discharge. Of these 22 subjects, 20 (90%) had a urinary creatinine clearance >50 mL/min and 18 (81%) had a creatinine clearance of >60 mL/min. Conclusion: Our prospective observations suggest that eGFR by C-G, MDRD-4, and KeGFR at 12, 24, and 48 hours, underestimates the GFR compared to urinary creatinine clearance for post-KTx functioning allograft recipients. We suggest adjusting post-KTx medications based on a 50% decrease in pre-transplant serum creatinine, where measured urinary creatine clearance is >50 mL/min in 92% of cases and >60 mL/min in 81% of cases. Renally dosed medication could be adjusted with a 50% decrease in serum creatinine in post-KTx. Future studies are required with exogenous glomerular filtration markers for more accurate formulae with functioning allografts in the immediate post-KTx period.Reference: 1.https://www.mdcalc.com/kinetic-estimated-glomerular-filtration-rate-kegfr

Metabolomics profile in acute respiratory distress syndrome by nuclear magnetic resonance spectroscopy in patients with community-acquired pneumonia

BackgroundAcute respiratory distress syndrome (ARDS) is a challenging clinical problem. Discovering the potential metabolic alterations underlying the ARDS is important to identify novel therapeutic target and improve the prognosis. Serum and urine metabolites can reflect systemic and local changes and could help understanding metabolic characterization of community-acquired pneumonia (CAP) with ARDS.MethodsClinical data of patients with suspected CAP at the First Affiliated Hospital of Wenzhou Medical University were collected from May 2020 to February 2021. Consecutive patients with CAP were enrolled and divided into two groups: CAP with and without ARDS groups. 1H nuclear magnetic resonance-based metabolomics analyses of serum and urine samples were performed before and after treatment in CAP with ARDS (n = 43) and CAP without ARDS (n = 45) groups. Differences metabolites were identifed in CAP with ARDS. Furthermore, the receiver operating characteristic (ROC) curve was utilized to identify panels of significant metabolites for evaluating therapeutic effects on CAP with ARDS. The correlation heatmap was analyzed to further display the relationship between metabolites and clinical characteristics.ResultsA total of 20 and 42 metabolites were identified in the serum and urine samples, respectively. Serum metabolic changes were mainly involved in energy, lipid, and amino acid metabolisms, while urine metabolic changes were mainly involved in energy metabolism. Elevated levels of serum 3-hydroxybutyrate, lactate, acetone, acetoacetate, and decreased levels of serum leucine, choline, and urine creatine and creatinine were detected in CAP with ARDS relative to CAP without ARDS. Serum metabolites 3-hydroxybutyrate, acetone, acetoacetate, citrate, choline and urine metabolite 1-methylnicotinamide were identified as a potential biomarkers for assessing therapeutic effects on CAP with ARDS, and with AUCs of 0.866 and 0.795, respectively. Moreover, the ROC curve analysis revealed that combined characteristic serum and urine metabolites exhibited a better classification system for assessing therapeutic effects on CAP with ARDS, with a AUC value of 0.952. In addition, differential metabolites strongly correlated with clinical parameters in patients with CAP with ARDS.ConclusionsSerum- and urine-based metabolomics analyses identified characteristic metabolic alterations in CAP with ARDS and might provide promising circulatory markers for evaluating therapeutic effects on CAP with ARDS.

P-125 Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6A8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC)

A proprietary in vivo target discovery screen identified creatine kinase-B (CKB) as a cancer driver in KRAS mutant (KRAS-mut) CRC. CKB promotes tumor growth and survival under hypoxia. CKB generates the energetic metabolite phospho-creatine (PCr), which is imported into cells through the creatine transporter, SLC6A8. PCr generates intracellular ATP that enables tumoral survival. RGX-202-01 is a small molecule inhibitor of SLC6A8 that depletes intracellular PCr and ATP, resulting in apoptosis. In a completed phase 1a study, RGX-202-01 monotherapy demonstrated objective anti-tumor activity in the relapsed/refractory KRAS-mut CRC setting without dose-limiting toxicity. The objectives of this ongoing phase 1b study are to evaluate safety, PK/PD, and efficacy of RGX-202-01 in combination with standard-of-care (SOC) FOLFIRI + BEV in second-line CRC, a setting where SOC therapy results in an ORR and mPFS of approximately 15% and 6 months, respectively. Subjects with advanced CRC who had disease progression after receiving a first-line oxaliplatin-containing regimen were eligible. As of 02-24-2022, 17 patients (pts) have been enrolled. 8 pts were enrolled in 2 dose escalation cohorts of RGX-202-01: 2400mg BID (4 pts) and 3000mg BID (4 pts) combined with FOLFIRI and BEV. 9 pts were enrolled in the dose expansion phase of the study and received RGX-202-01 3000mg BID combined with FOLFIRI and BEV. No DLTs were observed and the MTD was not reached in the dose escalation phase. Most common G2 TRAEs were nausea and diarrhea (50%) and most common G3 TRAEs were fatigue (12%) and hypertension (12%) There were no Grade 4-5 TRAEs. At the RP2D of 3000 mg BID, PK analysis showed sustained RGX-202-01 drug exposures above target levels (IC50). In addition, Serum and urine creatine measurements indicated robust SLC6A8 target inhibition (in both escalation cohort). 9 pts had KRAS-mut CRC, and all were evaluable for RECIST 1.1 response. 5 of these pts had PR (confirmed) and 4 pts have SD as best response (ORR 56%, DCR 100%). 5 of these pts remain on study for a duration ranging from 15-58 weeks. One patient with a PR at 16 weeks had surgery with curative intent and was observed off therapy with no evidence of disease until week 44 when a CT identified a recurrence. 8 pts had KRAS WT CRC. Of the 5 KRAS WT pts evaluable for response, 1 has a PR on first scan and is ongoing and 4 pts have SD as best response. (ORR 20%, DCR 100%)3 patients remain on study at 8, 20 and 24 weeks respectively. RGX-202-01 combined with FOLFIRI and BEV was well tolerated with no DLTs at the dose levels evaluated which induced potent inhibition of SLC6A8. Encouraging efficacy was observed in patients with RAS mutate mCRC, with 56% response rate exceeding that expected with SOC. Preferential activity in patients with RAS mutated tumors is consistent with pre-clinical studies. Enrollment in the expansion phase continues and a phase 2/3 trial in 2L CRC with RAS mut is planned.

Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6A8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC).

3579 Background: A proprietary in vivo target discovery screen identified creatine kinase-B (CKB) as a cancer driver in KRAS mutant (KRAS-mut) CRC. CKB promotes tumor growth and survival under hypoxia. CKB generates the energetic metabolite phospho-creatine (PCr), which is imported into cells through the creatine transporter, SLC6A8. PCr generates intracellular ATP that enables tumoral survival. RGX-202-01 is a small molecule inhibitor of SLC6A8 that depletes intracellular PCr and ATP, resulting in apoptosis. In a completed Phase 1a study, RGX-202-01 monotherapy demonstrated objective anti-tumor activity in the relapsed/refractory KRAS-mut CRC setting without dose-limiting toxicity. The objectives of this ongoing Phase 1b study are to evaluate safety, PK/PD, and efficacy of RGX-202-01 in combination with standard-of-care (SOC) FOLFIRI + BEV in second-line CRC, a setting where SOC therapy results in an ORR and mPFS of approximately 15% and 6 months, respectively. Methods: Subjects with advanced CRC who had disease progression after receiving a first line oxaliplatin-containing regimen were eligible. The dose expansion phase of the study was restricted to CKB-expressing CRC tumors. As of 01-14-2022, 16 patients (pts) have been enrolled. 8 pts were enrolled in 2 dose escalation cohorts of RGX-202-01: 2400mg BID (4 pts) and 3000mg BID (4 pts) combined with FOLFIRI and BEV. 8 pts were enrolled in the dose expansion phase of the study and received RGX-202-01 3000mg BID combined with FOLFIRI and BEV Results: No DLTs were observed and the MTD was not reached in the dose escalation phase. Grade 3 TRAEs were observed in 25% of pts. Most common TRAEs were GI in nature. There were no Grade 4-5 TRAEs. PK analysis showed sustained RGX-202-01 drug exposures in both escalation cohorts above target levels (IC50). Serum and urine creatine measurements indicated robust SLC6A8 target inhibition. 9 pts had KRAS-mut CRC, and all were evaluable for RECIST 1.1 response. 4 of these pts had cPR,1 patient had uPR and 4 pts had SD as best response (ORR 56%, DCR 100%). 5 of these pts remain on therapy ranging from 11-54 weeks and a patient with a cPR at 16 weeks followed by surgery with curative intent remains with NED at 24 weeks after surgery. Seven pts had KRAS WT CRC, of which 3 were evaluable (2 pts are pending 1st scan assessment; 2 pts are off study and did not receive 1 full cycle of treatment). Of the 3 KRAS WT evaluable pts, all had SD as best response. 2 were on study for 38 and 24 weeks respectively and 1 is ongoing at 16 weeks. Conclusions: RGX-202-01 combined with FOLFIRI and BEV was well tolerated with no DLTs at the dose levels evaluated which induced potent inhibition of SLC6A8. Antitumor activity was noted in KRAS mutated colorectal cancer, consistent with preferential pre-clinical activity in RAS mutated tumors. Enrollment in the expansion phase continues. Clinical trial information: NCT03597581.