Relative hypoxia and early diabetic kidney disease in type 1 diabetes

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The objective of this study was to compare the ratio of renal oxygen availability (RO2)toglomerularfiltration 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, HbA1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA1c 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 conclu-sion, 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.
Original languageEnglish
Pages (from-to)2700-2708
Number of pages9
JournalDiabetes
Volume69
Issue number12
DOIs
Publication statusPublished - 1 Dec 2020

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