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

Abstract


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
doi: https://doi.org/10.14740/jocmr4351

Keywords


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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