Dolphin-T1D Study: Define Renal Oxygenation Levels and Perfusion in Hyperfiltration in Adolescents w
Diabetic kidney disease (DKD) is the leading cause of renal failure in the United States, and a major risk factor for cardiovascular disease. Current treatments, such as control of hyperglycemia and hypertension, are beneficial, but only partially protective in patients with type 1 diabetes (T1D). Clinical trials in DKD have yielded disappointing results, partly due to limited understanding of what initiates DKD, a potentially misguided focus on albuminuria, and lack of intervention at an early stage of disease when benefit is most likely. Therefore, identifying new therapeutic targets to impede progression of DKD remains a public health priority. Early DKD, including hyperfiltration, is common in youth with T1D. Renal hypoxia, stemming from a mismatch between renal oxygen utilization and consumption, is increasingly proposed to be a unifying pathway in the development of DKD. The kidneys have a high-energy requirement to sustain normal hemodynamic function. However, in T1D, there are emerging animal data that the kidneys are not able to sufficiently compensate for hyperfiltration due to the effects of insulin resistance (IR) and mitochondrial dysfunction on fuel utilization. The pathophysiology underlying the relationship between early DKD and renal oxygenation (O2) in T1D is unclear. Accordingly, dedicated translational studies are needed to unravel the complex metabolic pathophysiology behind the development of DKD. Dr. Bjornstad is a young NIDDK funded investigator who is committed to patient-oriented research focused on early DKD. This DiaComp award would provide Dr. Bjornstad with the support necessary to define renal perfusion and O2 (by MRI) in youth with T1D with (n=15) and without (n=15) hyperfiltration by blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) MRI. This innovative application will capitalize on a Juvenile Diabetes Research Foundation funded study of youth with T1D undergoing gold standard assessment of intrarenal hemodynamic function by iohexol and para-aminohippurate clearance. To achieve these goals, Dr. Bjornstad has assembled a nationally-recognized co-investigator team consisting of Dr. Kristen Nadeau, Professor of Pediatric Endocrinology at University of Colorado, Denver (UCD), in addition a Dr. Pottumarthi Prasad (Radiology, U. of Chicago) and David Z. Cherney (Nephrology, U. of Toronto).