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Kidney Week

Abstract: FR-PO0491

SGLT2 Inhibitor Therapy Attenuates Endothelial Glycocalyx Injury and Reduces Interstitial Fluid Volume in Patients with CKD and Fluid Retention: The DAPA-BODY Trial

Session Information

Category: Cardiovascular-Kidney-Metabolic Health

  • 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

  • Sakai, Masato, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Masuda, Takahiro, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Asakura, Maki, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Oka, Kentaro, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Ohara, Ken, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Yuyama, Kosuke, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Hirai, Keiji, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Morinari, Masato, Shin-Oyama City Hospital, Oyama, Tochigi Prefecture, Japan
  • Akimoto, Tetsu, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Shimada, Kazuyuki, Shin-Oyama City Hospital, Oyama, Tochigi Prefecture, Japan
  • Nagata, Daisuke, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
  • Morishita, Yoshiyuki, Jichi Medical University, Shimotsuke, Tochigi Prefecture, Japan
Background

SGLT2 inhibitors improve renal and cardiovascular outcomes in patients with chronic kidney disease (CKD). Although these agents modulate body fluid homeostasis, the relationship between changes in body fluid distribution and endothelial glycocalyx injury remains unclear. We therefore investigated the effects of SGLT2 inhibitor therapy on serum syndecan-1, a marker of endothelial glycocalyx injury, and body fluid distribution in patients with CKD.

Methods

This prospective, nonrandomized, open-label study enrolled 55 patients with CKD who initiated dapagliflozin, an SGLT2 inhibitor. Body fluid status was assessed by bioimpedance analysis using the edema index, defined as extracellular water/total body water. Patients were stratified according to the edema index into a euvolemic group (edema index <0.40, n = 34) and a fluid retention group (edema index ≥0.40, n = 21). Serum syndecan-1 and body fluid parameters were evaluated at baseline and after 6 months of treatment. Estimated plasma volume was calculated using the Kaplan–Hakim formula, and estimated interstitial fluid volume (eIF) was derived by subtracting estimated plasma volume from extracellular water.

Results

Serum syndecan-1 significantly decreased in the fluid retention group from 50.9 ± 24.2 to 41.4 ± 15.4 ng/mL (p = 0.009), whereas no significant change was observed in the euvolemic group from 36.5 ± 14.8 to 36.5 ± 12.2 ng/mL (p = 0.09). eIF significantly decreased in the fluid retention group from 10.1 ± 2.6 to 9.5 ± 2.4 L (p = 0.017), whereas it modest increased in the euvolemic group from 11.1 ± 2.9 to 11.3 ± 2.9 L (P = 0.004). In the fluid retention group, percent changes in serum syndecan-1 showed a positive association with percent changes in eIF (r = 0.421, p = 0.08), whereas no such association was observed in the euvolemic group (r = 0.161, p = 0.40).

Conclusion

In patients with CKD, the effects of SGLT2 inhibitors on endothelial glycocalyx injury and interstitial fluid volume may differ according to baseline fluid status. Patients with fluid retention may be more likely to experience attenuation of endothelial glycocalyx injury accompanied by reductions in interstitial fluid volume during SGLT2 inhibitor therapy.

Funding

  • Private Foundation Support