A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope

Satoshi Miyamoto; Hiddo J L Heerspink; Dick de Zeeuw; Kota Sakamoto; Michihiro Yoshida; Masao Toyoda; Daisuke Suzuki; Takashi Hatanaka; Tohru Nakamura; Shinji Kamei; Satoshi Murao; Kazuyuki Hida; Shinichiro Ando; Hiroaki Akai; Yasushi Takahashi; Munehiro Kitada; Hisashi Sugano; Tomokazu Nunoue; Akihiko Nakamura; Motofumi Sasaki; Tatsuaki Nakatou; Kei Fujimoto; Daiji Kawanami; Takashi Wada; Nobuyuki Miyatake; Hiromi Kuramoto; Kenichi Shikata; CANPIONE study Investigators

doi:10.1016/j.kint.2024.08.019

A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope

Kidney Int. 2024 Nov;106(5):972-984. doi: 10.1016/j.kint.2024.08.019. Epub 2024 Aug 30.

Authors

Satoshi Miyamoto¹, Hiddo J L Heerspink², Dick de Zeeuw³, Kota Sakamoto⁴, Michihiro Yoshida⁴, Masao Toyoda⁵, Daisuke Suzuki⁶, Takashi Hatanaka⁷, Tohru Nakamura⁸, Shinji Kamei⁹, Satoshi Murao¹⁰, Kazuyuki Hida¹¹, Shinichiro Ando¹², Hiroaki Akai¹³, Yasushi Takahashi¹⁴, Munehiro Kitada¹⁵, Hisashi Sugano¹⁶, Tomokazu Nunoue¹⁷, Akihiko Nakamura¹⁸, Motofumi Sasaki¹⁹, Tatsuaki Nakatou²⁰, Kei Fujimoto²¹, Daiji Kawanami²², Takashi Wada²³, Nobuyuki Miyatake²⁴, Hiromi Kuramoto⁴, Kenichi Shikata⁴; CANPIONE study Investigators

Affiliations

¹ Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan; Department of Internal Medicine, Innoshima General Hospital, Onomichi, Japan. Electronic address: [email protected].
² Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: [email protected].
³ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
⁵ Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
⁶ Suzuki Diadetes Clinic, Atsugi, Japan.
⁷ Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center, Fukuyama, Japan.
⁸ Diabetes Internal Medicine, Sumitomo Besshi Hospital, Nihama, Japan.
⁹ Department of Diabetic Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
¹⁰ Department of Diabetes and Endocrinology, Takamatsu Hospital, Takamatsu, Japan.
¹¹ Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center, Okayama, Japan.
¹² Department of Internal Medicine Diabetic Center, Okayama City Hospital, Okayama, Japan.
¹³ Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
¹⁴ Department of Diabetes, Ochiai General Hospital, Maniwa, Japan.
¹⁵ Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan; Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
¹⁶ Department of Diabetes and Endocrinology, Kochi Health Sciences Center, Kochi, Japan.
¹⁷ Nunoue Clinic, Tsuyama, Japan.
¹⁸ Internal Medicine, Osafune Clinic, Setouchi, Japan.
¹⁹ Department of Diabetes and Endocrinology, Matsue City Hospital, Matsue, Japan.
²⁰ Diabetes Center, Okayama Saiseikai General Hospital, Okayama, Japan.
²¹ Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, Kashiwa, Japan.
²² Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan.
²³ Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
²⁴ Department of Hygiene, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan.

PMID: 39216659
DOI: 10.1016/j.kint.2024.08.019

Abstract

Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual's change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m² to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, -30.8% (95% confidence interval -42.6 to -16.8). The between-group difference (canagliflozin group - control group) of change in eGFR slope (chronic - pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m² per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD.

Keywords: CANPIONE study; canagliflozin; chronic kidney disease microalbuminuria; preintervention eGFR slope; sodium-glucose cotransporter 2 inhibitor.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Aged
Albuminuria* / diagnosis
Albuminuria* / drug therapy
Albuminuria* / urine
Canagliflozin* / therapeutic use
Creatinine / urine
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / physiopathology
Diabetic Nephropathies* / diagnosis
Diabetic Nephropathies* / drug therapy
Diabetic Nephropathies* / etiology
Diabetic Nephropathies* / physiopathology
Diabetic Nephropathies* / urine
Disease Progression*
Female
Glomerular Filtration Rate* / drug effects
Humans
Male
Middle Aged
Renal Insufficiency, Chronic* / drug therapy
Renal Insufficiency, Chronic* / physiopathology
Renal Insufficiency, Chronic* / urine
Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
Treatment Outcome

Substances

Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Creatinine