Abstract: FR-PO641

Does SGLT2 Inhibition with Dapagliflozin Overcome Therapy Resistance to RAAS Inhibition?

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Petrykiv, Sergei, None, Groningen, Groningen, Netherlands
  • Laverman, Gozewijn Dirk, ZGT Almelo, Almelo, Overijssel, Netherlands
  • de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands
Background

Renin-Angiotensin-Aldosterone-System inhibitors (RAASi) is a mainstay for renal and cardiovascular protective treatment in patients with chronic kidney disease. However, individual patients show a large variation in their response to RAASi both in surrogates like albuminuria and the hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) lower albuminuria and confer cardiovascular and possibly renal protection. To establish whether individual therapy resistance to RAASi can be overcome by adding an SGLT2 inhibitor we assessed individual albuminuria responses in patients exposed both to RAASi and the SGLT2 inhibitor dapagliflozin.

Methods

We used data from a randomized controlled cross-over trial designed to assess the albuminuria lowering effect of 6-weeks treatment with dapagliflozin. The trial enrolled 33 patients with type 2 diabetes, albumin:creatinine ratio (UACR) between 100 and 3500 mg/g who were all using an ACEI or ARB at the time of enrollment. We extracted from the electronic medical records data on the UACR response upon start of RAASi before the trial period, and analyzed the individual albuminuria response to RAASi and to dapagliflozin.

Results

We retrieved data on RAASi from 26 patients (age 62 (SD 8); male gender 20 (77%); UACR 355 [150 – 533] mg/g. Thirteen patients started an ACEi, and 13 an ARB before entry into the study. The mean UACR lowering response to RAASi was 26.5% with a large between individual variability (range -76.1 to +135.1%). The addition of dapaglifozin resulted in a mean UACR lowering response of 34.9%, again with a large between individual variability (range -83.9 to +94.2). Interestingly, there was a significant positive correlation between the response to RAASi and dapagliflozin (Pearson correlation coefficient 0.635; p<0.001) indicating that patients who did not respond to RAASi also did not respond to dapagliflozin. Therapy adherence during the study was excellent with 97.5% of all medications being taken.

Conclusion

Individual therapy resistance to RAASi cannot be overcome with the addition of a completely different class of drugs, SGLT-2 inhibitors. These data suggest that the individual drug response is an intrinsic individual characteristic possibly unrelated to the type of intervention, unless the mode of action of dapaglifozin on albuminuria is through the RAAS.

Funding

  • Commercial Support