306-OR: A Metabolic Mismatch between Renal Oxygenation and Glomerular Filtration Rate in Type 1 Diabetes
Authors: VINOVSKIS CARISSA L. , NADEAU KRISTEN J. , TOMMERDAHL KALIE L. , PRASAD POTTUMARTHI V. , LI LU-PING , PYLE LAURA , REWERS MARIAN , PRAGNELL MARLON , MAHMUD FARID H. , VAN RAALTE DANIËL H. , CHERNEY DAVID , NELSON ROBERT , BJORNSTAD PETTER 
Published: June 2020

Glomerular filtration rate (GFR) is a major determinant of renal energy expenditure. Animal models support a mismatch between renal oxygenation (RO2) and energy expenditure in diabetic kidney disease (DKD). The objective of this study was to compare the ratio of RO2 to GFR (RO2:GFR) in adolescents with and without type 1 diabetes (T1D) and correlate the ratio with albuminuria, effective renal plasma flow (ERPF), blood pressure, trunk mass and renal oxygen consumption. RO2 was measured by blood oxygenation level dependent (BOLD) MRI before and after 20 mg of I.V. furosemide, trunk mass by DXA, GFR by iohexol clearance, ERPF by p-aminohippurate clearance and albuminuria by urine albumin-to-creatinine ratio (UACR) in 50 adolescents with T1D (mean age 16.1±3.0 yrs, trunk mass 44.8±2.2%, HbA1c 8.6±1.2%, GFR 189±40 ml/min) and 20 non-obese controls (mean age 16.1±2.9 yrs, trunk mass 44.9±2.2%, HbA1c 5.2±0.2%, GFR 136±22 ml/min). The RO2:GFR (s/ml/min*1000) was calculated as renal oxygenation (T2*, s) divided by GFR (ml/min), and furosemide-suppressible oxygenation (FSOC) as change in RO2 in responses to furosemide. Relationships were evaluated by correlation and multivariable generalized linear regression models. RO2:GFR was 25% lower in adolescents with T1D vs. controls (mean±SD: 0.24±0.04 vs. 0.32±0.04, p&lt;0.0001). In adolescents with T1D, lower RO2:GFR was associated with higher UACR (r=-0.31, p=0.03), diastolic blood pressure (r=-0.33, p=0.02), ERPF (r=-0.52, p=0.0009) and trunk mass (r=-0.39, p=0.006). Lower RO2:GFR was also associated with elevated FSOC after adjustments for age, sex and HbA1c (β±SE: -10.5±3.2, p=0.002). For the first time, we demonstrate an imbalance between RO2 and GFR in adolescents with T1D compared with healthy non-obese controls. Additionally, low RO2:GFR independently associated with albuminuria, central adiposity and elevated renal oxygen consumption. These data suggest a potential role of relative renal hypoxia in the development of early DKD.

Disclosure
C.L. Vinovskis: None. K.J. Nadeau: None. K.L. Tommerdahl: None. P.V. Prasad: None. L. Li: None. L. Pyle: None. M. Rewers: None. M. Pragnell: None. F.H. Mahmud: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation. D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Sanofi. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. R. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma.

Funding
JDRF (2-SRA-2018-627-M-B); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116720)