Renal Hemodynamic Function at the Extremes of T1D Duration-Adolescents vs. Adults with T1D for =50 Years

Abstract

Our aim was to better understand kidney function changes and RAAS activation over the natural history of T1D in patients with a wide range of T1D duration. GFRinulin and ERPFPAH were measured during a euglycemic clamp before and after an angiotensin II infusion (ANGII, 3 ng·kg-1·min-1-a measure of RAAS activation) in patients with T1D: 28 adolescents (age 16.2±2.0 years), 54 young adults (25.4±5.6 years) and 66 adults with ≥50 years of T1D (65.7±7.5 years) from the Canadian Study of Longevity. Gomez’s equations were used to estimate afferent (RA) and efferent (RE) arteriolar resistances and glomerular hydrostatic pressure (PGLO). In a step-wise fashion, GFRinulin, ERPFPAH, PGLO decreased, renal vascular resistance (RVR) and RA increased in adolescents vs. young adults vs. adults with ≥50 years of T1D (Figure 1). RE was similar in adolescents vs. young adults, but was higher in patients with ≥50 years of T1D. ANGII resulted in blunted renal hemodynamic responses in patients with ≥50 years of T1D (RVR increase of 0.033±0.016 vs. 0.049±0.019mmHg/L/min in adolescents, p=0.0006) suggesting a state of enhanced RAAS activation. With longer duration of disease, patients with T1D have evidence of renal vasoconstriction, leading to lower GFRinulin, ERPFPAH, elevated RVR and RAAS activation. Further work is required to understand the potential role of non-RAAS, pharmacologic agents that target RA in patients with early T1D. Disclosure Y. Lytvyn: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. M. Farooqi: None. V.S. Lai: None. J.M. Tse: None. L. Cham: None. L. Lovblom: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. E.B. Sochett: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..