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Renin-angiotensin-aldosterone system activation in long-standing type 1 diabetes

Julie A Lovshin1,2, Geneviève Boulet3, Yuliya Lytvyn2

  • 1Division of Endocrinology and Metabolism and.

JCI Insight
|January 12, 2018
PubMed
Abstract

Insights

In type 1 diabetes, exaggerated renin-angiotensin-aldosterone system (RAAS) activity, particularly in the afferent arteriole, distinguishes those who develop diabetic kidney disease from those who resist it.

Area of Science:

  • Nephrology
  • Endocrinology
  • Cardiovascular Research

Background:

  • Type 1 diabetes (T1D) management often includes RAAS inhibitors to prevent kidney disease.
  • However, the reasons some T1D patients develop diabetic kidney disease (DKD) while others do not (DKD resistors) remain unclear.
  • This study investigates the role of RAAS activation in DKD development in T1D.

Purpose of the Study:

  • To determine if individuals with diabetic kidney disease (DKD) exhibit distinct patterns of renin-angiotensin-aldosterone system (RAAS) activation compared to DKD resistors in long-standing type 1 diabetes (T1D).
  • To assess endogenous RAAS activation by measuring changes in renal vascular resistance (RVR) following exogenous RAAS stimulation.

Main Methods:

  • Compared hemodynamic function in 75 T1D patients and controls before and after angiotensin II infusion.
  • Measured changes in renal vascular resistance (RVR) as a primary outcome to assess endogenous RAAS activation.
  • Differentiated between DKD, DKD resistors, and controls.

Main Results:

  • Individuals with DKD showed less change in RVR after RAAS stimulation, indicating heightened endogenous RAAS activation compared to DKD resistors and controls.
  • While efferent arteriolar resistance changes were similar in all T1D groups, DKD patients exhibited reduced afferent arteriolar vascular resistance changes, suggesting increased RAAS activity.
  • These findings point to an exaggerated intrarenal RAAS in DKD, predominantly affecting the afferent arteriole.

Conclusions:

  • In long-standing T1D, diabetic kidney disease is associated with an exaggerated intrarenal renin-angiotensin-aldosterone system (RAAS).
  • This heightened RAAS activity unexpectedly occurs at the afferent arteriole, leading to vasoconstriction.
  • Understanding this mechanism may offer new therapeutic targets for preventing DKD in T1D.
Keywords:
DiabetesEndocrinologyNephrology

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