Relative hypoxia and early diabetic kidney disease in type 1 diabetes
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posted on 2020-07-31, 16:43 authored by Ada AdminAda Admin, Carissa Vinovskis, Lu-Ping Li, Pottumarthi Prasad, Kalie Tommerdahl, Laura Pyle, Robert G. Nelson, Meda E. Pavkov, Daniel van Raalte, Marian Rewers, Marlon Pragnell, Farid H. Mahmud, David Z. Cherney, Richard J. Johnson, Kristen J. Nadeau, Petter BjornstadThe 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.