Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes

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.