LAUSR

Objectives: We aimed to examine the effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor on systemic and intrarenal renin-angiotensin system (RAS) activity in subtotally nephrectomized non-diabetic rats, a model of chronic kidney disease (CKD). Methods: Plasma renin activity (PRA) and angiotensin II content of renal tissue were measured by a radioimmunoassay. Plasma intact- and total-angiotensinogen levels were measured by ELISA kits, respectively. Then, the amount of des (angiotensin I)-angiotensinogen (calculated as total-angiotensinogen - intact-angiotensinogen) and the ratio of des (angiotensin I)-angiotensinogen to intact-angiotensinogen in the plasma were determined to estimate how much intact-angiotensinogen is cleaved by renin in plasma. Results: Oral administration of a selective SGLT2 inhibitor, TA-1887 (10 mg/kg/day), for 10 weeks significantly increased urinary volume and glucose excretion. However, plasma renin activity, intact- and total-angiotensinogen levels, and the ratio of des (angiotensin I)-angiotensinogen to intact-angiotensinogen in the plasma were not changed. Furthermore, treatment with TA-1887 did not change kidney angiotensin II contents and renal injury. Conclusion: These data suggest that chronic treatment with a SGLT2 inhibitor does not deteriorate renal function in subjects with CKD, which is associated with maintenance of systemic and intrarenal RAS activity.