Initial Acute Decline in Estimated Glomerular Filtration Rate After Sodium-Glucose Cotransporter-2 Inhibitor in Patients With Chronic Kidney Disease

Seigo Sugiyama, Akira Yoshida, Kunio Hieshima, Noboru Kurinami, Katsunori Jinnouchi, Motoko Tanaka, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi, Hideaki Jinnouchi


Background: Renal function deterioration accompanied by an acute decrease in estimated glomerular filtration rate (eGFR) was observed early after starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy. It is unclear how much and how frequently the initial acute decline in eGFR (IAD-eGFR) would occur after SGLT2i administration, and the effects of IAD-eGFR on subsequent renal function are unknown in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD).

Methods: We retrospectively recruited T2DM patients with CKD (stage 3b; 30 ? eGFR < 45 mL/min/1.73 m2) and who were newly treated with add-on SGLT2i. We further investigated the effects of SGLT2i therapy on eGFR early after starting treatment (1 - 3 months) and after 6 months of treatment. We examined the factors associated with a large IAD-eGFR (? 10%) using logistic regression analyses.

Results: Eighty-seven patients (male, 74.7%; mean age, 69.8 years; median hemoglobin A1c, 7.3%; mean eGFR, 37.8 mL/min/1.73 m2) were analyzed. The mean minimum eGFR early after SGLT2i administration was 34.9 mL/min/1.73 m2, which was significantly lower than before treatment (mean, -7.7%). Seventy patients (80.5%) had IAD-eGFR, and 36 patients (41.4%) had a large IAD-eGFR (? 10%). Overall, the mean eGFR was 38.2 at 6 months after starting SGLT2i administration. In patients with a large IAD-eGFR (? 10%), the eGFR decreased by 72.2% at 6 months to 35.5 mL/min/1.73 m2, showing a significant decline from the pretreatment value. In patients without a large IAD-eGFR, eGFR increased by 66.7% at 6 months to 40.0 mL/min/1.73 m2. Multiple logistic regression analysis showed that patients with a large IAD-eGFR had a significant association with a high estimated daily salt intake.

Conclusions: SGLT2i treatment frequently induced a significant decrease in eGFR early after starting therapy, but eGFR tended to recover after 6 months in T2DM patients with CKD stage 3b. A large IAD-eGFR (? 10%) caused by SGLT2i may lead to subsequent deterioration in renal function, and it was significantly associated with a higher estimated daily salt intake. These results suggest that a more effective renoprotective therapeutic strategy using SGLT2i may be implemented by avoiding the occurrence of a large IAD-eGFR. Further prospective studies are warranted.

J Clin Med Res. 2020;12(11):724-733


Sodium-glucose cotransporter-2 inhibitors; Estimated glomerular filtration rate; Chronic kidney disease; Initial acute decline in eGFR; Type 2 diabetes mellitus; Renoprotection; Estimated daily salt intake; Tubuloglomerular feedback

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