Kidney Week

Abstract: SA-PO519

Effects of RAAS Activation on Intrarenal Inflammation and Intrarenal Hemodynamics: Results from the Canadian Study of Longevity in Type I Diabetes

Session Information

• Diabetic Kidney Disease: Basic - III
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Sridhar, Vikas, University of Toronto, Toronto, Ontario, Canada

Vikas Sridhar,

• Ambinathan, Jaya Prakash Nath, University of Toronto, Toronto, Ontario, Canada

Jaya Prakash Nath Ambinathan,

• Lovblom, Leif Erik, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

Leif Erik Lovblom,

• Lytvyn, Yuliya, University of Toronto, Toronto, Ontario, Canada

Yuliya Lytvyn,

• Bjornstad, Petter, University of Colorado School of Medicine, Aurora, Colorado, United States

Petter Bjornstad,

• Perkins, Bruce A., University of Toronto, Toronto, Ontario, Canada

Bruce A. Perkins,

• Cherney, David, University of Toronto, Toronto, Ontario, Canada

David Cherney,

• Lovshin, Julie A., University of Toronto, Toronto, Ontario, Canada

Julie A. Lovshin,

Background

Inflammation and pro-fibrotic pathways are implicated in the pathogenesis of diabetic kidney disease (DKD) and are activated by chronic hyperglycemia and renin angiotensin aldosterone system (RAAS) stimulation. Quantification of urinary inflammatory markers has been used in type I diabetes (T1D) to determine renal tissue inflammation. The relationship between RAAS activation, intrarenal inflammation and hemodynamics is unknown. To study this, we measured the excretion of urine inflammatory markers and GFR in participants with longstanding T1D compared to adult comparators without diabetes following exogenous RAAS activation.

Methods

A urinary cytokine 42-plex panel adjusted for urine creatinine was analyzed from participants of the Canadian Study of Longevity in T1D of more than 50 years duration (n=74) and compared to age and sex matched adult comparators without diabetes (n=73). Renal hemodynamic function was measured using inulin and p-aminohippurate (PAH). Changes in urinary inflammatory marker excretion post angiotensin II (AngII) infusion were compared between comparators, and T1D participants with and without DKD (resistors). Renal hemodynamic function was correlated with urinary inflammatory markers independent of A1c, T1D duration, and systolic blood pressure.

Results

The renal hemodynamic response to AngII in this cohort has been previously published, with an attenuated response in DKD vs. DKD resistors and controls, likely signifying high baseline RAAS activation. Conversely, in this analysis, RAAS activation stimulated a significant increase in the urinary excretion of 31 inflammatory markers in both DKD and DKD resistors, compared to adults without diabetes (p<0.05). There were no differences in inflammatory marker excretion between participants with DKD and resistors. Inulin_GFR inversely correlated with urinary excretion of proinflammatory markers (IL-18, IP-10, & RANTES), growth factor receptors (PDGF-AA & VEGFAA), and chemokines (Eotaxin & MCP-1).

Conclusion

RAAS activation was associated with increased markers of intrarenal inflammation in T1D participants with and without DKD, suggesting a consistent role for RAAS activation at the renal tissue level leading to inflammation even after longstanding T1D.