PT - JOURNAL ARTICLE AU - Vinovskis, Carissa AU - Li, Lu-Ping AU - Prasad, Pottumarthi AU - Tommerdahl, Kalie AU - Pyle, Laura AU - Nelson, Robert G. AU - Pavkov, Meda E. AU - van Raalte, Daniel AU - Rewers, Marian AU - Pragnell, Marlon AU - Mahmud, Farid H. AU - Cherney, David Z. AU - Johnson, Richard J. AU - Nadeau, Kristen J. AU - Bjornstad, Petter TI - Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes. AID - 10.2337/db20-0457 DP - 2020 Jul 30 TA - Diabetes PG - db200457 4099 - http://diabetes.diabetesjournals.org/content/early/2020/07/30/db20-0457.short 4100 - http://diabetes.diabetesjournals.org/content/early/2020/07/30/db20-0457.full AB - The objective of this study was to compare the ratio of renal oxygen availability (RO2) to GFR (RO2:GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygenation level dependent (BOLD) MRI, fat mass by DXA, GFR and RPF by iohexol and p-aminohippurate clearance, albuminuria by urine albumin-to-creatinine ratio (UACR), and M/I from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (16.1±3.0 years, HbA1c 8.6±1.2%) and 20 controls of similar BMI (16.1±2.9 years, HbA1c 5.2±0.2%). The RO2:GFR (ms/ml/min) was calculated as renal oxygen availability (T2*, ms) divided by GFR (ml/min). Whole-kidney RO2:GFR was 25% lower in adolescents with T1D vs. controls (p<0.0001). In adolescents with T1D, lower whole-kidney RO2:GFR associated with higher UACR (r=-0.31, p=0.03), RPF (r=-0.52, p=0.0009) and fat mass (r=-0.33, p=0.02). Lower medullary RO2:GFR associated with lower M/I (r=0.31, p=0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that associated with albuminuria, increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of DKD.