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

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. GFR inulin and ERPF PAH 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 (R A ) and efferent (R E ) arteriolar resistances and glomerular hydrostatic pressure (P GLO ). In a step-wise fashion, GFR inulin , ERPF PAH , P GLO decreased, renal vascular resistance (RVR) and R A increased in adolescents vs. young adults vs. adults with ≥50 years of T1D (Figure 1). R E 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 GFR inulin , ERPF PAH , elevated RVR and RAAS activation. Further work is required to understand the potential role of non-RAAS, pharmacologic agents that target R A 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 u0026 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. Speaker9s Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker9s 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 u0026 Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..