Effect of sodium-glucose cotransport inhibition on polycystic kidney disease progression in PCK rats

44Citations
Citations of this article
46Readers
Mendeley users who have this article in their library.

Abstract

The sodium-glucose-cotransporter-2 (SGLT2) inhibitor dapagliflozin (DAPA) induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD), we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d) or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group). Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d) and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d). DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min) and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min) after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

References Powered by Scopus

Tolvaptan in patients with autosomal dominant polycystic kidney disease

1293Citations
N/AReaders
Get full text

Autosomal dominant polycystic kidney disease

1162Citations
N/AReaders
Get full text

Polycystic kidney disease

662Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Sodium glucose cotransporter 2 inhibition in the diabetic kidney: An update

89Citations
N/AReaders
Get full text

Metabolic reprogramming in autosomal dominant polycystic kidney disease evidence and therapeutic potential

81Citations
N/AReaders
Get full text

Dapagliflozin in focal segmental glomerulosclerosis: A combined human-rodent pilot study

75Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Kapoor, S., Rodriguez, D., Riwanto, M., Edenhofer, I., Segerer, S., Mitchell, K., & Wüthrich, R. P. (2015). Effect of sodium-glucose cotransport inhibition on polycystic kidney disease progression in PCK rats. PLoS ONE, 10(4). https://doi.org/10.1371/journal.pone.0125603

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

53%

Researcher 5

29%

Professor / Associate Prof. 3

18%

Readers' Discipline

Tooltip

Medicine and Dentistry 14

64%

Agricultural and Biological Sciences 5

23%

Biochemistry, Genetics and Molecular Bi... 2

9%

Pharmacology, Toxicology and Pharmaceut... 1

5%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 2

Save time finding and organizing research with Mendeley

Sign up for free