The effect of the sodium-glucose cotransporter type-2 inhibitor dapagliflozin on glomerular filtration rate in healthy cats

Arnon Gal, S. E. Burton, K. Weidgraaf, P. Singh, N. Lopez-Villalobos, A. Jacob, U. Malabu, R. Burchell

Research output: Contribution to journalArticle

Abstract

Sodium-glucose cotransporter type-2 inhibitors (SGLT2is) reduce glomerular hyperfiltration in diabetic people with early diabetic nephropathy. The objective of this report was to assess changes in glomerular filtration rate in healthy cats after treatment with a SGLT2i. Eight healthy research adult castrated male cats were used in a randomized, controlled, cross-over study design. We induced isolated renal tubular glucosuria by dosing cats with the SGLT2i dapagliflozin. The cats received by mouth 10 mg dapagliflozin or control every 24 h in each of the 4, 5-d trial periods that were separated by a 7-d washout period. We assessed glomerular filtration rate (iohexol clearance method), serum urea, creatinine, symmetric dimethylarginine, and 24-h sodium and chloride urinary excretion on the fifth day of each trial period. We analyzed the data with a mixed linear model that included the fixed effects of treatment (treated and control) and trial period, and the random effect of the cat. Compared with controls, cats treated with dapagliflozin had a significant increase in mean (±SE) glomerular filtration rate (3.1 ± 0.2 vs 2.5 ± 0.2 mL/kg/min; P = 0.01), whereas there were no significant differences in serum urea, creatinine and symmetric dimethylarginine, and 24-h urine sodium and chloride excretion. We propose that dapagliflozin-mediated delivery of sodium and glucose distal from the proximal convoluted tubule induced compensatory increased sodium absorption at the thick ascending loop of Henle that resulted in decreased sodium delivery to the distal tubule leading to tubuloglomerular feedback–mediated glomerular hyperfiltration. Future studies should determine if SGLT2is' renoprotective effect in people can be enhanced with the addition of a Na+-K+-Cl diuretic and whether dapagliflozin will be useful in mitigating proteinuria and hypertension that follow glomerular hyperfiltration in diabetic companion animals in a similar mechanism as in people.

Original languageEnglish (US)
Article number106376
JournalDomestic Animal Endocrinology
Volume70
DOIs
StatePublished - Jan 2020

Fingerprint

Sodium-Glucose Transport Proteins
glomerular filtration rate
Glomerular Filtration Rate
Cats
sodium
cats
glucose
Sodium
Sodium Chloride
Cross-Over Studies
Urea
Creatinine
Renal Glycosuria
Iohexol
Loop of Henle
creatinine
Pets
chlorides
Diabetic Nephropathies
renoprotective effect

Keywords

  • Cat
  • Diabetes mellitus
  • Diabetic nephropathy
  • Glomerular sclerosis
  • Renal glucose handling
  • SGLT2

ASJC Scopus subject areas

  • Food Animals
  • Animal Science and Zoology
  • Endocrinology

Cite this

The effect of the sodium-glucose cotransporter type-2 inhibitor dapagliflozin on glomerular filtration rate in healthy cats. / Gal, Arnon; Burton, S. E.; Weidgraaf, K.; Singh, P.; Lopez-Villalobos, N.; Jacob, A.; Malabu, U.; Burchell, R.

In: Domestic Animal Endocrinology, Vol. 70, 106376, 01.2020.

Research output: Contribution to journalArticle

Gal, Arnon ; Burton, S. E. ; Weidgraaf, K. ; Singh, P. ; Lopez-Villalobos, N. ; Jacob, A. ; Malabu, U. ; Burchell, R. / The effect of the sodium-glucose cotransporter type-2 inhibitor dapagliflozin on glomerular filtration rate in healthy cats. In: Domestic Animal Endocrinology. 2020 ; Vol. 70.
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