Application of the D3 -creatine muscle mass assessment tool to a geriatric weight loss trial: A pilot study.

BACKGROUND: Traditionally, weight loss (WL) trials utilize dual energy X-ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non-bone and non-fat tissue, is a reasonable proxy for muscle mass. In contrast, the D3 -creatine (D3 Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D3 Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength. METHODS: The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three-armed, 12-month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D3 Cr tracer dose, provided a fasted urine sample 3-6 days post-dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid-thigh and trunk muscle/intermuscular fat areas) scans, and performed 400-m walk, stair climb, knee extensor strength, and grip strength tests. RESULTS: Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m2 ). Six month total body WL was -10.3 (95% confidence interval, CI: -12.7, -7.9) kg. All DXA and computed tomography-derived body composition measures were significantly decreased from baseline, yet D3 Cr muscle mass did not change [+0.5 (95% CI: -2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline. CONCLUSIONS: Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6-month period was associated with significant declines in all bioimaging metrics, while D3 Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D3 Cr muscle mass by parent trial treatment group assignment in all study participants.

Albuminuria Testing by Race and Ethnicity among Patients with Hypertension with and without Diabetes.

BACKGROUND: Detection of chronic kidney disease (CKD) with urine albumin-to-creatinine ratio (UACR) among patients with hypertension (HTN) provides an opportunity for early treatment, potentially mitigating risk of CKD progression and cardiovascular complications. Differences in UACR testing patterns among racial/ethnic populations at risk for CKD could contribute to known disparities in CKD complications. METHODS: We examined the prevalence of UACR testing among low-income adult primary care patients with HTN, defined by a new administrative code for HTN or 2 clinic blood pressures >140/90 mm Hg between January 1, 2014, and January 1, 2017, in one public health-care delivery system with a high prevalence of end-stage kidney disease among race/ethnic minorities. Logistic regression was used to identify odds of UACR testing within 1 year of a HTN diagnosis, overall, and by racial/ethnic subgroup, adjusted for demographic factors, estimated glomerular filtration rate, and HTN severity. Models were also stratified by diabetes status. RESULTS: The cohort (n = 16,414) was racially/ethnically diverse (16% White, 21% Black, 34% Asian, 19% Hispanic, and 10% other) and 51% female. Only 35% of patients had UACR testing within 1 year of a HTN diagnosis. Among individuals without diabetes, odds of UACR testing were higher among Asians, Blacks, and Other subgroups compared to Whites (adjusted OR [aOR] 1.19; 95% CI 1.00-1.42 for Blacks; aOR 1.33; 1.13-1.56 for Asians; aOR 1.30; 1.04-1.60 for Other) but were not significantly different between Hispanics and Whites (aOR 1.17; 0.97-1.39). Among individuals with diabetes, only Asians had higher odds of UACR testing compared to Whites (aOR 1.35; 1.12-1.63). CONCLUSIONS: Prevalence of UACR testing among low-income patients with HTN is low in one public health-care delivery system, with higher odds of UACR testing among racial/ethnic minority subgroups compared to Whites without diabetes and similar odds among those with diabetes. If generalizable, less albuminuria testing may not explain higher prevalence of kidney failure in racial/ethnic minorities.

Assessment of lifestyle effect on oxidative stress biomarkers in free-living elderly in rural Japan.

BACKGROUND: Oxidative stress is believed to play a crucial role in aging and age-related diseases, and is widely thought to increase morbidity and mortality in the elderly. Assessment of biomarkers of oxidative stress, such as 8-isoprostane and 8-hydroxy-2-deoxyguanosine, are considered to be useful in predicting disease risks at the population level. OBJECTIVE: The aim of the present study was to assess the health status of the elderly by comparing their lifestyles and levels of oxidative stress biomarkers. METHODS: We carried out a cross-sectional study where urine samples from a total of 100 elderly men and women were assayed for 8-isoprostane, 8-hydroxy-2-deoxyguanosine, selenium, cadmium and creatinine. They were asked to answer a questionnaire that included questions about their lifestyle. RESULTS: Most of the participants were prehypertensive, non-alcohol users and on a rich plant-based diet. There were no differences in any biomarkers of oxidative stress between men and women. 8-Isoprostane was found to correlate positively with systolic blood pressure in women, but not in men. There was a slight increase of 8-isoprostane in participants with a poor intake of vegetables, and a decrease of 8-hydroxy-2-deoxyguanosine in participants who consumed fish. Multiple regression analysis showed that oxidative stress biomarkers were positively associated with cadmium, and negatively associated with selenium and fish intake in all participants, 89% of which were non-smokers. CONCLUSION: Results from the present study show that fish intake has the potential of decreasing oxidative stress among elderly persons.

Assessment of novel avian renal disease markers for the detection of experimental nephrotoxicosis in pigeons (Columba livia).

Renal disease is a major cause of illness in captive and wild avian species. Current renal disease markers (e.g., uric acid, blood urea nitrogen, and creatinine) are insensitive. Two endogenous markers, creatine and N-acetyl-beta-D-glucosaminidase (NAG), were selected for study in the pigeon (Columba livia). Representative organs from four pigeons were surveyed to determine those exhibiting the highest level of each marker. In a separate study, NAG and creatine from plasma and urine were assayed before and after gentamicin (50 mg/kg twice daily), administration for up to 9 days. Observer-blinded pathologic scoring (five saline solution controls, 17 treated birds) was used to verify the presence of renal disease that corresponded to marker increases. The first study revealed that kidney tissue had the highest NAG activity (by approximately six times), and pectoral muscle had the most creatine (>900 times). In response to gentamicin, plasma creatine (>five times) and NAG increased (approximately six times), which paralleled uric acid (>10 times). Urine creatine (approximately 60 times) and NAG increased dramatically (approximately 50 times) in response to gentamicin. In conclusion, NAG, especially in the urine, may be of value to noninvasively detect renal toxin exposures and to monitor potentially nephrotoxic drugs, and might be of value to screen free-ranging birds in large exhibits or in the wild by assaying fresh urate samples at feeding stations.

Assessment of Hg contamination and exposure to miners and schoolchildren at a small-scale gold mining and recovery operation in Thailand.

Gold extracted by Hg-amalgamation process, which can cause both health and environmental problems, is widespread in South East Asia including Myanmar, Laos, Cambodia, and Thailand. Small-scale gold mining operations have been carried out since the year 2000 in Phanom Pha District, Phichit Province, Thailand. Since no data is available for evaluating Hg exposure, an investigation of mercury (Hg) contamination and exposure assessment was carried out at this mine site. Environmental monitoring illustrated the total Hg in water was as high as 4 microg/l while Hg in sediment ranged between 102 to 325 microg/kg dry weight. Both Hg deposition from the air (1.28 microg/100 cm(2)/day) and concentration in surface soil (20,960 microg/kg dry weight) were elevated in the area of amalgamation. The potential of Hg exposure to miners as well as to schoolchildren was assessed. The concentrations of Hg in urine of 79 miners who were directly (group I) or indirectly (group II) involved in the gold recovery operation were 32.02 and 20.04 microg/g creatinine, respectively, which did not exceed regulatory limits (35 microg/g creatinine). Hair Hg levels in both groups (group I and group II) also were not significantly higher than the non-exposed group. In terms of risk factors, gender and nature of food preparation and consumption were the two significant variables influencing the concentration of Hg in urine of miners (P < 0.05). A hazard quotient (HQ) was estimated based on the inorganic Hg exposure of individual miners. The HQ values of group I were in a range 16 to 218 times higher than the safety level set as 1. By comparison the group II HQ index was very low (0.03-0.39). The miners in group I who worked and ate food from this area experienced potentially high exposure to Hg associated with the mining process. In a second Hg exposure assessment, a group of 59 schoolchildren who attended an elementary school near the gold mine site was evaluated for Hg exposure. A slightly higher Hg urine concentration was detected in group I and group II (involved and not involved in gold recovery) at average levels of 15.82 and 9.95 microg/g creatinine, respectively. The average Hg values for both groups were below the established levels indicating no risk from Hg intake. Average Hg hair level in all schoolchildren (0.93 microg/g) was not significantly higher than reference group. There were two variables (gender and personal hygiene) which affected the concentration of Hg in urine of schoolchildren (P < 0.05). The result (HQ) also suggested that schoolchildren were not at risk (< 1). Schoolchildren involved in gold mining activities showed some indirect exposure to Hg from the adults working in mining area.

Urine albumin/creatinine ratio for the assessment of albuminuria in pregnancy hypertension.

BACKGROUND: An accurate method to assess albuminuria in pregnancy is mandatory to diagnose pre-eclampsia. Twenty-four-hour urine collection is still the only universally accepted method. This is, however, a cumbersome and inconvenient method. Therefore, the present study aimed at assessing the accuracy of a spot urine albumin/creatinine ratio in pregnant women with hypertension. MATERIAL AND METHODS: In 54 pregnant women with blood pressure >or=140/90 mmHg, 24-h albumin excretion and subsequent albumin/creatinine ratio on morning spot urine were analyzed in the individual patients. Altogether 75 paired samples were included. Receiver operating characteristic curves, relating different albumin/creatinine ratio cut-off values to 24-h albumin excretion >300 mg were constructed. Correlations were assessed by Spearman rank correlation tests. RESULTS: The area under the receiver operating characteristic curve was 0.985. At the optimal cut-off albumin/creatinine ratio value of 27 mg/mmol the sensitivity, specificity, positive and negative predictive value for detecting albuminuria >300 mg/24 h were: 95, 100, 100 and 86% respectively. There was a close correlation between albumin/creatinine ratio and 24-h albumin excretion values (r=0.95; p<0.001). CONCLUSIONS: It is suggested that in most cases the more cumbersome 24-h urine collection can be replaced by the more convenient albumin/creatinine ratio on spot urine.

Urinary levels of creatine and other metabolites in the assessment of polymyositis and dermatomyositis.

BACKGROUND: A simple and reliable method is needed to assess disease activity and monitor the efficacy of therapy in polymyositis (PM) and dermatomyositis (DM). This study used in vitro proton ((1)H) magnetic resonance spectroscopy (MRS) to explore whether excretion of urinary metabolites can be used as a reliable marker of disease in PM and DM patients. METHODS: Urine samples were obtained from PM/DM patients (n=34), healthy controls (50) and subjects with known muscle-wasting conditions including adult-onset muscular dystrophy (8), stroke patients (10), rheumatoid arthritis (RA) patients on steroids (13) and not on steroids (16) and patients with alcoholic myopathy (12). Levels of urinary metabolites were then correlated with creatine kinase (CK) activities and quadriceps muscle strength. RESULTS: Creatine was detected in the urine in 26 of 35 patients with PM/DM, four of 60 cases with other medical disorders (including one with adult-onset dystrophy, one with a stroke and two with RA who were not on steroids) and 10 of 50 healthy controls. The urinary creatine/creatinine ratio exceeded 0.4 in 20 patients with PM/DM but no patients with other medical disorders and no healthy controls. These differences were highly significant (P<0.001) by Kruskal-Wallis test (comparing all groups) and by Mann-Whitney U-tests (comparing individual groups with PM/DM cases). Citrate, glycine, choline-containing compounds and taurine levels were significantly increased in PM/DM when compared with controls. There were positive correlations between CK activities and choline-containing compounds (r=0.78, P=0.0006) and also between CK activities and betaine (r=0.57, P=0.026). CONCLUSIONS: This study shows significant differences in the urinary levels of creatine, choline-containing metabolites, betaine and citrate in PM/DM subjects compared with controls, although further work is required to elucidate the underlying metabolic processes.

Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies.

BACKGROUND: Disorders of creatine metabolism arise from genetic alterations of arginine:glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT), and the creatine transporter. We developed a strategy for the detection of AGAT and GAMT defects by measurement of guanidinoacetate (GAA) and creatine plus creatinine (Cr+Crn) in biological fluids. METHODS: Three patients with AGAT deficiency from the same pedigree and their eight relatives, as well as a patient affected by a GAMT defect and his parents were analyzed by a new HPLC procedure in comparison with 90 controls. The method, which uses precolumn derivatization with benzoin, separation with a reversed-phase column, and fluorescence detection, has shown good precision and sensitivity and requires minimal sample handling. RESULTS: In the three AGAT patients, plasma GAA was 0.01-0.04 micro mol/L [mean (SD) for neurologically normal controls was 1.16 (0.59) micromol/L], Cr+Crn was 15-29 micro mol/L [reference limit in our laboratory, 79 (38) micromol/L]. Urinary GAA was 2.4-5.8 micro mol/L [reference, 311 (191) micromol/L], and Cr+Crn was 2.1-3.3 mmol/L [reference, 9.9 (4.1) mmol/L]. We found a smaller decrease in GAA and Cr+Crn in some carriers of an AGAT defect. In the patient with GAMT deficiency, plasma and urine GAA was increased (18.6 and 1783 micromol/L, respectively), and Cr+Crn was decreased in plasma (10.7 micromol/L) and urine (2.1 mmol/L). GAA was increased in the parents' plasmas and in the mother's urine. CONCLUSION: The assessment of GAA is a new tool for the detection of both GAMT and AGAT deficiencies.

An assessment of genetic markers as predictors of bone turnover in healthy adults.

In 1992 a significant relationship between bone turnover and the vitamin D receptor (VDR) genotype was reported in Australian subjects of UK-Irish decent. Since then, several groups have investigated the relationship between VDR and other bone-related genotypes, bone mass and bone turnover in several populations. However, the results of these studies are conflicting. Therefore, our aim was to determine bone-related genotypes in a population of healthy Irish adults and relate these genotypes to the rate of bone turnover. One hundred and eighteen healthy Irish adults (aged 19-67 yr) were recruited and fasting blood and first void urines were collected from each subject. Bone-related genotype frequencies in healthy Irish adults were similar to those reported in other Caucasian populations and were in Hardy-Weinberg equilibrium. Estrogen receptor (Pvu II or Xba I), apolipoprotein E and collagen IA1 genotypes were not related to bone turnover. The tt VDR genotype was associated with significantly higher serum osteocalcin (29% and 40%) compared with the Tt and TT genotypes, respectively. The ff VDR genotype was associated with significantly higher urinary pyridinoline (by approximately 44% and approximately 29%) and deoxypyridinoline (by approximately 76% and approximately 58%) levels and higher serum osteocalcin (by approximately 25% and approximately 53%) compared with the Ff or FF genotypes, respectively. These findings suggest that healthy Irish adults with either the tt or ff VDR genotype have higher rates of bone turnover than those with Tt or TT, or Ff or FF genotypes, respectively, and therefore may have a higher risk of low bone mineral density and osteoporosis in later life.

Protein creatinine index and Albustix in assessment of proteinuria.

The protein creatinine index in early morning and random urine specimens was compared with the 24 hour urinary excretion of protein in normal subjects and outpatients with abnormal proteinuria. A protein creatinine index (defined as (mg protein/1 divided by creatinine mmol/1) times 10) below 125 in a random specimen excluded abnormal proteinuria, whereas an index of more than 136 indicated the presence of pathological proteinuria. The index for random specimens provided a useful semiquantitative assessment of the 24 hour excretion of protein (mg protein/24 hours), but the index for early morning specimens was less reliable. Errors with Albustix were partly due to intra and inter observer variations in the interpretation of the colour formed when compared with the chart provided. It is proposed that the protein creatinine index on random urine samples should be used to supplement dipsticks in screening for proteinuria in cases where misclassification would be serious.

Assessment of nutritional status: the biochemical approach and its problems in liver disease.

The role of laboratory tests in the assessment of nutritional status is reviewed. Methods commonly used in evaluating adequacy of energy, protein, mineral and vitamin intake are discussed, and a protocol for nutritional assessment and monitoring is presented. The specific nutritional problems found in liver disease, and the effects these have on this protocol are considered.