Kidney Week

Abstract: SA-PO138

Effects of Dapagliflozin on Albuminuria, Renal Function, and Renin-Angiotensin-Aldosterone Hormones in Type 2 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Eickhoff, Mie K., Steno Diabetes Center Copenhagen, Gentofte, Denmark

Mie K. Eickhoff,

• Frimodt-Moller, Marie, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Marie Frimodt-Moller,

• Jørgensen, Niklas Rye, Rigshospitalet, Glostrup, Denmark

Niklas Rye Jørgensen,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

• Persson, Frederik, Steno Diabetes Center, Gentofte, Denmark

Frederik Persson,

Background

Sodium glucose cotransporter 2 inhibitors (SGLT2i) have shown a cardio- and renoprotective effect. The mechanism for this effect and the interaction with the renin-angiotensin-aldosterone system (RAAS) is only partially understood. Therefore, we aim to evaluate the effect of dapagliflozin treatment on albuminuria, measured GFR, 24h blood pressure (BP) and hormone levels of the RAAS when added to standard care including RAAS blocking treatment in patients with type 2 diabetes (T2D).

Methods

Double-masked randomized placebo-controlled crossover trial of 12 weeks treatment with dapagliflozin 10 mg or matching placebo. All patients were treated with RAAS blocking treatment. Included patients (n=40) had T2D and albuminuria at baseline. At the end of the treatment periods 3 consecutive morning spot urines were collected as well as 24h BP measurement and ⁵¹Cr-EDTA clearance performed.
Values at the end of treatment periods (placebo vs. dapagliflozin) were compared using mixed model analysis.

Results

Baseline age was 65 (SD±8), 90% were male, HbA_1c was 73 mmol/mol (SD±15), 24h BP 148/82 mmHg (SD±12.5/7.7), geometric mean urinary albumin creatinine ratio (UACR) 147 (IQR 75-289) mg/g and mean eGFR 85 ml/min/1.72 m² (SD±19.7).
After 12 weeks treatment UACR was reduced 36% (95% CI 16-56%) during treatment with dapagliflozin vs. placebo (p<0.01), GFR decreased 10.9 (5-16) ml/min/1.72 m² (p<0.01), HbA1c was reduced 7.4 (5-10) mmol/mol (p<0.01) and 24h BP 4.8/2.7 mmHg (p=0.023/0.031). Plasma renin concentration increased 37% (9-66%, p = 0.012), plasma renin activity increased 41% (7—74%, p = 0.019), angiotensin II increased 37% (1-73%, p = 0.046) whereas plasma aldosterone was unchanged.

Conclusion

When added to standard RAAS blocking treatment dapagliflozin 10 mg vs. placebo once daily was associated with a significant reduction in albuminuria, 24h BP and GFR in patients with T2D and albuminuria. A concomitant increase in RAAS hormones was observed, possibly caused by increased diuresis as an effect of natriuresis.

Funding

• Commercial Support – AstraZeneca