The Combined Oral Stable Isotope Assessment of Muscle (COSIAM) reveals D-3 creatine derived muscle mass as a standout cross-sectional biomarker of muscle physiology vitality in older age.

Validated diagnostics of skeletal muscle vitality could benefit clinical and basic science in terms of mechanistic insights and in determining the efficacy of interventions, e.g. exercise/pharmaceuticals/nutrients. We recently developed a Combined Oral Assessment of Muscle (COSIAM) that can be used to simultaneously quantify whole-body muscle mass (WBMM), muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Here, we aimed to establish, in a cross-sectional fashion, links between COSIAM parameters and established aspects of muscle function. We recruited 37 healthy older adults (male (M):female (F) (21/16); 72 ± 5 y)) into a 3-day trial. Subjects consumed D3-creatine (D3-Cr dilution to assess WBMM), D2O (MPS by incorporation of alanine) and D3-3-methylhistidine (D3-MH dilution to assess MPB). A biopsy at day 3 was used to determine MPS, and blood/urine samples were collected to determine D3-Cr/D3-MH dilution for WBMM and MPB. Physiological measures of muscle mass (e.g. DXA/ultrasound) and function (e.g. handgrip strength, maximum voluntary contraction (MVC), one-repetition maximum (1-RM)) were ascertained. A stepwise linear regression approach was used to address links between facets of COSIAM (MPS, MPB, WBMM) and muscle physiology. Despite expected differences in muscle mass, there were no significant differences in MPS or MPB between sexes. WBMM as measured using D3-Cr positively correlated with DXA-derived lean body mass (LBM) and appendicular LBM (ABLM). Stepwise linear regression was used to assess which combination of MPS, MPB, D3-Cr and absolute synthesis rate (ASR) best predicted physiological measures of muscle health in these older adults. D3-Cr WBMM alone was the best predictor of handgrip, 1RM and MVC, and outperformed more traditional measures of muscle mass by DXA. The COSIAM approach substantiates D3-Cr as a robust biomarker of multiple muscle physiology health biomarkers. Future work using COSIAM should focus upon how and which parameters it can inform upon in relation to disease progression and the efficacy of interventions.

Combined in vivo muscle mass, muscle protein synthesis and muscle protein breakdown measurement: a 'Combined Oral Stable Isotope Assessment of Muscle (COSIAM)' approach.

Optimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits the applicability of these approaches in certain populations (e.g. clinical, frail elderly). To concurrently quantify skeletal muscle mass and muscle protein turnover i.e. muscle protein synthesis (MPS) and muscle protein breakdown (MPB), in elderly human volunteers using stable-isotope labelled tracers i.e. Methyl-[D3]-creatine (D3-Cr), deuterium oxide (D2O), and Methyl-[D3]-3-methylhistidine (D3-3MH), to measure muscle mass, MPS and MPB, respectively. We recruited 10 older males (71 ± 4 y, BMI: 25 ± 4 kg.m2, mean ± SD) into a 4-day study, with DXA and consumption of D2O and D3-Cr tracers on day 1. D3-3MH was consumed on day 3, 24 h prior to returning to the lab. From urine, saliva and blood samples, and a single muscle biopsy (vastus lateralis), we determined muscle mass, MPS and MPB. D3-Cr derived muscle mass was positively correlated to appendicular fat-free mass (AFFM) estimated by DXA (r = 0.69, P = 0.027). Rates of cumulative myofibrillar MPS over 3 days were 0.072%/h (95% CI, 0.064 to 0.081%/h). Whole-body MPB over 6 h was 0.052 (95% CI, 0.038 to 0.067). These rates were similar to previous literature. We demonstrate the potential for D3-Cr to be used alongside D2O and D3-3MH for concurrent measurement of muscle mass, MPS, and MPB using a minimally invasive design, applicable for clinical and frail populations.

Application of dynamic contrast enhanced ultrasound in the assessment of kidney diseases.

PURPOSE OF REVIEW: Many forms of acute and chronic disease are linked to changes in renal blood flow, perfusion, vascular density and hypoxia, but there are no readily available methods to assess these parameters in clinical practice. Dynamic contrast enhanced ultrasound (DCE-US) is a method that provides quantitative assessments of organ perfusion without ionising radiation or risk of nephrotoxicity. It can be performed at the bedside and is suitable for repeated measurements. The purpose of this review is to provide updates from recent publications on the utility of DCE-US in the diagnosis or assessment of renal disease, excluding the evaluation of benign or malignant renal masses. RECENT FINDINGS: DCE-US has been applied in clinical studies of acute kidney injury (AKI), renal transplantation, chronic kidney disease (CKD), diabetic kidney disease and to determine acute effects of pharmacological agents on renal haemodynamics. DCE-US can detect changes in renal perfusion across these clinical scenarios and can differentiate healthy controls from those with CKD. In sepsis, reduced DCE-US measures of perfusion may indicate those at increased risk of developing AKI, but this requires confirmation in larger studies as there can be wide individual variation in perfusion measures in acutely unwell patients. Recent studies in transplantation have not provided robust evidence to show that DCE-US can differentiate between different causes of graft dysfunction, although it may show more promise as a prognostic indicator of graft function 1 year after transplant. DCE-US can detect acute haemodynamic changes in response to medication that correlate with changes in renal plasma flow as measured by para-aminohippurate clearance. SUMMARY: DCE-US shows promise and has a number of advantages that make it suitable for the assessment of patients with various forms of kidney disease. However, further research is required to evidence its reproducibility and utility before clinical use can be advocated.