Spatial metabolomics for human kidney interrogation of early diabetic kidney disease


Center University of Colorado Denver
Award Year 2020
Pilot Study Spatial metabolomics for human kidney interrogation of early diabetic kidney disease
Awardee Petter Bjornstad MD ORCiD
Abstract

Kidney hypoxia, stemming from a mismatch between increased renal energy demand and impaired substrate metabolism, is emerging as a unifying early pathway in the development of diabetic kidney disease (DKD) and a potential therapeutic target. In our JDRF-funded CROCODILE study we are quantifying kidney O2 consumption by 11C-acetate PET, kidney oxygenation by blood oxygen level dependent MRI, glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearances, morphometric and transcriptomic analyses of kidney tissue from research biopsies, insulin sensitivity by hyperinsulinemic-euglycemic clamp and mitochondrial function by plasma and urine metabolomics in young adults with and without type 1 diabetes (T1D). However, plasma and urine metabolomics are not kidney-specific and identified compounds may not be representative of the intrarenal milieu. Accordingly, metabolic phenotyping of the kidney tissue to interrogate tissue-specific metabolic perturbations of early DKD in T1D would enhance our study design. The DRC P&F Grant would provide support to add spatial metabolomics analyses of kidney tissues by matrix-assisted laser desorption/ ionization mass spectrometry imaging from young adults with (n=20) and without (n=20) T1D. Our central objective is to quantify metabolite data in discrete kidney compartments in order to define the metabolic pathways that may drive early DKD in T1D.