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Abstract: FR-PO608

The Diuretic Actions of SGLT2 Inhibitors and Loop Diuretics Induce Different Compensating Mechanisms

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Masuda, Takahiro, Jichi Medical University, Shimotsuke, TOchigi, Japan
  • Muto, Shigeaki, Jichi Medical University, Shimotsuke, TOchigi, Japan
  • Fukuda, Keiko, Jichi Medical Universtiy, Shimotsuke, Tochigi, Japan
  • Watanabe, Minami, Jichi Medical Universtiy, Shimotsuke, Tochigi, Japan
  • Ohara, Ken, Jichi Medical University, Shimotsuke, TOchigi, Japan
  • Vallon, Volker, University of California San Diego, San Diego, California, United States
  • Nagata, Daisuke, Jichi Medical University, Shimotsuke, TOchigi, Japan
Background

We recently reported that SGLT2 inhibitor ipragliflozin (Ipra) exhibits a sustained diuretic and natriuretic tone that activates compensatory increases in fluid and food intake, and solute-free water reabsorption to stabilize body fluid volume (Am J Physiol Renal Physiol 2018, ASN Kidney Week 2018). Here we determined whether loop diuretics activate similar compensatory mechanisms.

Methods

Sprague-Dawley rats were treated by oral gavage with vehicle (Veh), loop diuretic furosemide (FR) [50mg/kg] or Ipra [5mg/kg] (n= 4-8) in metabolic cages for 1 week. Bioimpedance spectroscopy (ImpediVet) was used to assess body water on days 0 and 7.

Results

FR and Ipra increased urine volume (Veh 18±2, FR 27±3, Ipra 31±2 mL/day [average of 7 days], ANOVA p=0.006), but FR did not increase fluid intake (41±4, 37±6, 51±5 mL/day, p=0.188) and food intake (23±1, 8±3, 23±3 mL/day, p=0.009). As a result, FR significantly decreased fluid balance (fluid intake-urine volume) (23±2, 10±3, 21±4 mL/day, p=0.010). Urine vasopressin (1.5±0.3, 0.7±0.3, 2.4±0.4 ng/day, day 3, p=0.024) and renal solute-free water reabsorption (84±10, 42±11, 128±7 mL/day, day 7, p<0.001) were decreased in the FR group and increased in the Ipra group. Serum osmolality was similar among the groups (307±3, 311±3, 305±2 mOsm/kgH2O, day 7, p=0.357). The change in total body water (+8±7, -34±8, -5±3 mL, from day 0 to day 7, p<0.001) and creatinine clearance (5.8±0.3, 2.7±0.6, 5.6±0.2 L/day, day 7, p=0.025) were significantly decreased in the FR group.

Conclusion

The SGLT2 inhibitor maintained body fluid volume and renal function. The loop diuretic decreased both parameters with the impaired solute-free water reabsorption unexpectedly being associated with a lack of compensatory increases in vasopressin secretion and fluid intake.

Funding

  • Government Support - Non-U.S.