fumarates and Renal-Insufficiency

We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics.. Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF.. In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion.. ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Adolescent; Albuminuria; Carboxylic Acids; Diabetes Mellitus, Type 1; Fumarates; Glomerular Filtration Rate; Glycine; Histidine; Humans; Kidney; Malates; Phenylalanine; Renal Insufficiency

Topics: Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Early Termination of Clinical Trials; Fumarates; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency

Topics: Amides; Antihypertensive Agents; Biological Availability; Blood Pressure; Drug Interactions; Fumarates; Humans; Hypertension; Renal Insufficiency; Renin; Renin-Angiotensin System