RESEARCH COMMUNICATIONS OF THE 28th ECVIM-CA CONGRESS

Osmotic diuresis is the currently accepted mechanism of polyuria in diabetes mellitus and ostensibly leads to polyuria‐mediated functional volume depletion. Consequently, a compensatory increase in glomerular filtration rate (GFR) is expected. The latter has not been documented, and we hypothesized that glucosuria would increase GFR and aimed to measure the GFR in a model of isolated renal glycosuria. We randomized eight cats in a crossover design to receive 10 mg dapagliflozin (a type‐2 sodium glucose transporter inhibitor) or sham‐treatment over four, 5‐day treatment periods that were separated by 7‐day washout periods. We assessed GFR and total body water content (TBWC) via iohexol clearance and deuterium‐oxide tracer dilution method, respectively. The study had a power of 90% to detect a difference of 20±15 mL in daily urine output. We analyzed the results with a mixed effect model that included treatment and period of treatment as fixed effects. To control for the effect of repeated measures on the same cat, a random intercept for cat and an autoregressive process of order‐1 correlation structure were fitted. Statistical significance was set at 0.05. Dapagliflozin induced profound glucosuria without an increase in daily urine output. The mean (±SE) iohexol clearance was 3.5±0.3 and 4.2±0.2 for the nontreated and sham‐treated cats, respectively (P 0.003). The mean (±SE) TBWC, normalized to body weight, was 65.1±2.4% and 64.1±1.2%, for the sham‐treated and treated cats, respectively (P 0.43). We conclude that in this model, the observed increase in GFR is associated with a concomitant preservation of TBWC.