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Abstract: FR-PO1075

An Evaluation of Renin-Angiotensin System Markers in Youth with Type 2 Diabetes and Associations with Renal Outcomes

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Dart, Allison, University of Manitoba, Winnipeg, Manitoba, Canada
  • Wicklow, Brandy, University of Manitoba, Winnipeg, Manitoba, Canada
  • Scholey, James W., University of Toronto, Toronto, Ontario, Canada
  • Sellers, Elizabeth Ann cameron, University of Manitoba, Winnipeg, Manitoba, Canada
  • Mahmud, Farid H., Hospital for Sick Children, Toronto, Ontario, Canada
  • Sochett, Etienne Bertrand, Hospital for Sick Children, Toronto , Toronto, Ontario, Canada
  • Hamilton, Jill, Hospital for Sick children, Toronto, Ontario, Canada
  • Blydt-Hansen, Tom D., University of British Columbia, Vancouver, British Columbia, Canada
  • Burns, Kevin D., The Ottawa Hospital - Riverside Campus, Ottawa, Ontario, Canada

Group or Team Name

  • Diabetes Research Envisioned and Accomplished in Manitoba (DREAM)
Background

Activation of the renin-angiotensin system (RAS) is associated with diabetic kidney disease in adults, and may also have prognostic significance in youth. We evaluated serum and urine RAS markers in youth with T2D and associations with albuminuria status, glycemic control, eGFR and blood pressure.

Methods

This is a cross sectional analysis of 183 youth with T2D and 100 controls from the iCARE cohort. Youth further stratified by albuminuria status (ACR < or >2mg/mmol (Alb)) and ACEi/ARB excluded. RAS levels measured with ELISA and enzyme activities measured by synthetic substrates. Differences in levels between groups were evaluated. For T2D group, levels log transformed and Tobit regressions evaluated for associations with ACR, HbA1c, eGFR and 24 BP loads (correcting for age, sex, BMIz-score and duration of diabetes).

Results

Mean age 14.7 yrs, duration of diabetes 1.7 years and 21.3% with Alb. Serum PRA (p=0.0006), aldosterone (p=0.004) and sACE activity (p=0.005) were higher in T2D than controls (C). uACE (0.1 (C), 1.2 (T2D) and 2.0 (Alb) ng/mgCr; p<0.001) and uACE2 activity (6.0 (C), 160.8 (T2D), 505.2 (Alb) ng/mgCr; p<0.001) also increased. In mulitvariable regressions, higher aldosterone (p=0.02), urinary AGT (p<0.0001), and ACE2 activity (p=0.009) associated with albuminuria. Higher AGT and urinary ACE2 protein and activity associated with higher HbA1c. No associations seen between RAS marker and eGFR or BP loads.

Conclusion

RAS activation is present in youth with T2D. The prognostic and therapeutic significance of the combined effect of glycemia and RAS activation on renal outcomes requires additional investigation.

Funding

  • Government Support - Non-U.S.