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. 2020 Nov;12(11):724-733.
doi: 10.14740/jocmr4351. Epub 2020 Nov 3.

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

Seigo Sugiyama  1   2 , Akira Yoshida  3 , Kunio Hieshima  4 , Noboru Kurinami  5 , Katsunori Jinnouchi  6   7 , Motoko Tanaka  8 , Tomoko Suzuki  1 , Fumio Miyamoto  9 , Keizo Kajiwara  1   5 , Tomio Jinnouchi  1   5 , Hideaki Jinnouchi  1   10   2
Affiliations

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

Seigo Sugiyama et al. J Clin Med Res. 2020 Nov.

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.

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

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Conflict of interest statement

Dr. Seigo Sugiyama is on the Speaker’s Bureau of MSD, Inc., and AstraZeneca Pharmaceuticals LP, Ono Pharmaceutical Co., Ltd., and Bayer Yakuhin Ltd. Dr. Hideaki Jinnouchi has received consultant fees from Sanofi U.S., Novo Nordisk, Inc., and Eli Lilly Japan K.K. Dr. Hideaki Jinnouchi is also on the Speaker’s Bureau of MSD, Inc., Astellas Pharma US, Inc., Sanofi U.S., Novo Nordisk Pharma, Ltd., Taisho Pharmaceutical, Co., Ltd. Daiichi-Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly Japan K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited, and AstraZeneca Pharmaceuticals LP. All other authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
IAD-eGFR after starting SGLT2i therapy in T2DM patients with CKD stage 3b. The line graph indicates serial changes in eGFR before and early after treatment with SGLT2is. The serial changes in eGFR were analyzed by Student’s paired t-test (n = 87, P < 0.01). SGLT2i: sodium-glucose cotransporter-2 inhibitor; eGFR: estimated glomerular filtration rate; IAD-eGFR: initial acute decline in eGFR; SEM: standard error of mean; SD: standard deviation.
Figure 2
Figure 2
Distribution of percent changes in IAD-eGFR after starting SGLT2i therapy in T2DM patients with CKD stage 3b. Bar histogram indicates patient number in each percent change in eGFR. eGFR: estimated glomerular filtration rate; IAD-eGFR: initial acute decline in eGFR; SGLT2i: sodium-glucose cotransporter-2 inhibitor; T2DM: type 2 diabetes mellitus; CKD: chronic kidney disease.
Figure 3
Figure 3
Proportion of IAD-eGFR after starting SGLT2i therapy in T2DM patients with CKD stage 3b. (a) Proportion of any eGFR decline in and (b) proportion of large eGFR decline more than 10%. eGFR: estimated glomerular filtration rate; IAD-eGFR: initial acute decline in eGFR; SGLT2i: sodium-glucose cotransporter-2 inhibitor; T2DM: type 2 diabetes mellitus; CKD: chronic kidney disease.
Figure 4
Figure 4
Time course effects of IAD-eGFR after starting SGLT2i therapy on levels of 6 months eGFR in T2DM patients with CKD stage 3b. The line graph indicates serial changes in eGFR before and after treatment with SGLT2is according to the degree of IAD-eGFR. eGFR: estimated glomerular filtration rate; IAD-eGFR: initial acute decline in eGFR; SGLT2i: sodium-glucose cotransporter-2 inhibitor; T2DM: type 2 diabetes mellitus; CKD: chronic kidney disease.
Figure 5
Figure 5
Time course effects of large IAD-eGFR (≥ 10%) after starting SGLT2i therapy on levels of 6 months eGFR in T2DM patients with CKD stage 3b. The line graph indicated serial changes in eGFR before and after treatment with SGLT2is according to the presence or absence of large IAD-eGFR (≥ 10%). eGFR: estimated glomerular filtration rate; IAD-eGFR: initial acute decline in eGFR; SGLT2i: sodium-glucose cotransporter-2 inhibitor; T2DM: type 2 diabetes mellitus; CKD: chronic kidney disease; SEM: standard error of mean.
Figure 6
Figure 6
Effects of large IAD-eGFR (≥ 10%) after starting SGLT2i therapy on the changes in 6 months eGFR in T2DM patients with CKD stage 3b. eGFR: estimated glomerular filtration rate; IAD-eGFR: initial acute decline in eGFR; SGLT2i: sodium-glucose cotransporter-2 inhibitor; T2DM: type 2 diabetes mellitus; CKD: chronic kidney disease.
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