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 glomerular filtration rate (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 oxygen level-dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA_1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA_1c 5.2 ± 0.2%). The RO₂:GFR (ms/mL/min) was calculated as RO₂ (T2*, ms) divided by GFR (mL/min). Whole-kidney RO₂:GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO₂:GFR was 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 was associated with lower M/I (r = 0.31, P = 0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.