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Relative hypoxia and early diabetic kidney disease in type 1 diabetes

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posted on 31.07.2020 by Ada 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 Bjornstad
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.

Funding

Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255 (18AU3871 [P.B.]), JDRF grant number 2-SRA-2018-627-M-B (P.B.), and NIH/NIDDK grant number K23-DK116720 (P.B.), K24-HL145076 (K.J.N.), UL1-RR025780 (University of Colorado Denver), support from Center for Women’s Health Research at University of Colorado, the Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine, and by the Intramural Research Program of the NIDDK.

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