Anticoagulant Citrate Dextrose Solution (Formula A) 8ml pre-filled syringes

BackgroundDapagliflozin (DAPA) has shown major nephroprotective effects, improving kidney metabolism and oxigenation. Lipidomics and metabolomics are powerful tools for understanding such effects, providing a comprehensive look at how SGLT2 inhibitors might change the metabolic landscape beyond their primary glucose-lowering action. We investigated changes in plasma metabolomic/lipidomic profile and urinary excretion of metabolites that could occur independent of increased diuresis.MethodsA two-armed, parallel-design, randomized clinical trial was conducted in subjects with type 2 diabetes and hypertension who received treatment with DAPA 10 mg/day or hydrochlorothiazide 12.5 mg/day for four weeks. Lipidomics and metabolomics were performed by high resolution mass spectrometry in fasting plasma and 24-hour urine samples collected before and after treatment.ResultsCompared to hydrochlorothiazide, DAPA significantly increased plasma isoleucine, methionine, citrate, β-hydroxybutyrate and decreased lactate. DAPA induced plasma lipid remodeling towards a significant raise in free fatty acids (FFAs) and some sphingomyelins and lysophosphatidylcholines containing these fatty acids. A significant change was observed in plasma medium- and short-chain acylcarnitines, positively correlated with changes in plasma FFAs and β-hydroxybutyrate. In addition, DAPA, but not hydrochlorothiazide, significantly increased 24-h urinary excretion of several amino-acids, lactate, TCA cycle metabolites, β-hydroxybutyrate and electrolytes, except for a decrease in malate excretion.ConclusionsDAPA treatment has major effects on the plasma lipidomic and the urine metabolomic profiles, with significant increased renal excretion of several metabolites, especially amino-acids, independently of increased diuresis. These data offer insights into the complex metabolic pathways leading to kidney protection by SGLT2 inhibitors.Clinical trial informationEuropean Union Drug Regulating Authorities Clinical Trials No. 2015-004164-11.

Abstract licence: CC BY-NC-ND

IntroductionIntravenous crystalloid fluid infusion is a mandatory nutritional intervention received by surgical patients. Crystalloids vary in the pH value and electrolyte balance when administered; these effects directly alter plasma and urine compositions and can considerably affect the patient's intraoperative metabolism.MethodsThis randomized controlled study compared 0.9% saline solution and lactated Ringer's solution in terms of intraoperative metabolism among 56 patients undergoing lumbar spinal surgery. Blood and urine samples were obtained before and after surgery for arterial blood gas analysis and untargeted metabolomic analysis using liquid chromatography-mass spectrometry.ResultsPatients receiving 0.9% saline developed hyperchloremic acidosis and exhibited higher postoperative plasma concentrations of sodium (interaction P = 0.008) and glucose (interaction P = 0.034). They also required higher intraoperative norepinephrine doses (18 [0-43] μg vs. 0 [0-5] μg; P P = .051); significantly higher oxaloacetate concentrations (interaction P = .015), which may indicate less intraoperative gluconeogenesis (interaction P = .015); lower leucine degradation metabolite concentration, namely hydroxyisocaproic acid (interaction P = .055); and an attenuated decline in anti-inflammatory phospholipid breakdown metabolite, namely 15-ketoeicosatetraenoic acid (interaction P = .063). By contrast, patients receiving 0.9% saline solution exhibited unfavorable metabolism in urine indicated by reduced excretion of citric acid and creatine, which correlated with reduced glomerular filtration rates.ConclusionsThe administration of lactated Ringer's solution may facilitate more favorable intraoperative metabolic profiles than the administration of 0.9% saline solution during lumbar spinal surgery.

Abstract licence: CC BY