Kidney international reports · 2026
Cystatin C Confirms the Canagliflozin eGFR Slope Benefit in CANPIONE.
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Miyamoto Satoshi, Heerspink Hiddo J L, de Zeeuw Dick, Sakamoto Kota, Yoshida Michihiro, Toyoda Masao, Suzuki Daisuke, Hatanaka Takashi, Nakamura Tohru, Kamei Shinji, Murao Satoshi, Hida Kazuyuki, Ando Shinichiro, Akai Hiroaki, Takahashi Yasushi, Kitada Munehiro, Sugano Hisashi, Nunoue Tomokazu, Nakamura Akihiko, Sasaki Motofumi, Nakatou Tatsuaki, Fujimoto Kei, Kawanami Daiji, Wada Takashi, Miyatake Nobuyuki, Kuramoto Hiromi, Shikata Kenichi
Аннотация
INTRODUCTION: In the canagliflozin in type 2 diabetic patients with microalbuminuria in Japanese population (CANPIONE) study with a novel preintervention slope design, canagliflozin attenuated the decline in creatinine-based estimated glomerular filtration rate (eGFR-creatinine) slope in patients with type 2 diabetes mellitus and microalbuminuria. However, because serum creatinine is affected by muscle mass, the reliability of the eGFR-creatinine slope may be limited. Therefore, this prespecified exploratory analysis aimed to evaluate the effect of canagliflozin on the cystatin C-based eGFR (eGFR-cystatin C) slope, which is less affected by muscle mass, to validate the robustness of the previous findings.
METHODS: The chronic eGFR-cystatin C and eGFR-creatinine slopes were assessed using a 2-slope linear spline mixed-effects model. Pearson correlation coefficients were used to evaluate associations between changes in eGFR and body composition-related parameters.
RESULTS: eGFR trajectories were directionally consistent across both filtration markers. The chronic eGFR-cystatin C slopes in the canagliflozin and control groups were -0.4 (95% confidence interval [CI], -2.6 to 1.8) and -4.9 (-7.1 to -2.6) ml/min per 1.73 m2/year, respectively, corresponding to a between-group difference of 4.4 (1.3-7.6) ml/min per 1.73 m2/year. Similar trends were observed in the eGFR-creatinine slopes derived from the same time points, yielding a comparable treatment effect on the chronic slope (between-group difference: 3.5 [0.2-6.8] ml/min per 1.73 m2/year). Canagliflozin reduced body weight, body mass index (BMI), and waist circumference, whereas little correlation was observed between these changes and changes in eGFR-cystatin C.
CONCLUSION: Incorporating the eGFR-cystatin C slope analysis supports the robustness of the previous creatinine-based slope findings, suggesting that the eGFR-creatinine slope analysis retains reasonable clinical reliability in patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is).
METHODS: The chronic eGFR-cystatin C and eGFR-creatinine slopes were assessed using a 2-slope linear spline mixed-effects model. Pearson correlation coefficients were used to evaluate associations between changes in eGFR and body composition-related parameters.
RESULTS: eGFR trajectories were directionally consistent across both filtration markers. The chronic eGFR-cystatin C slopes in the canagliflozin and control groups were -0.4 (95% confidence interval [CI], -2.6 to 1.8) and -4.9 (-7.1 to -2.6) ml/min per 1.73 m2/year, respectively, corresponding to a between-group difference of 4.4 (1.3-7.6) ml/min per 1.73 m2/year. Similar trends were observed in the eGFR-creatinine slopes derived from the same time points, yielding a comparable treatment effect on the chronic slope (between-group difference: 3.5 [0.2-6.8] ml/min per 1.73 m2/year). Canagliflozin reduced body weight, body mass index (BMI), and waist circumference, whereas little correlation was observed between these changes and changes in eGFR-cystatin C.
CONCLUSION: Incorporating the eGFR-cystatin C slope analysis supports the robustness of the previous creatinine-based slope findings, suggesting that the eGFR-creatinine slope analysis retains reasonable clinical reliability in patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is).