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

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/1.73m<sup>2</sup> 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 m<sup>2</sup> 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.

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Publication Details

Journal
Kidney International
Published
2024-08-30
DOI
https://doi.org/10.1016/j.kint.2024.08.019
Citations
7
Primary Topic
Diabetes Treatment and Management
Type
article
Field-Weighted Citation Impact
2.50

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article

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

Tatsuaki Nakatou, Kazuyuki Hida, Nobuyuki Miyatake, Satoshi Murao et al.
7 citations
Kidney International
Diabetes Treatment and Management
2.50
article

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

Tatsuaki Nakatou, Kazuyuki Hida, Nobuyuki Miyatake, Satoshi Murao, Hiddo J.L. Heerspink, Yasushi Takahashi, Hisashi Sugano, Hiroaki Akai, Shin’ichiro Ando, Dick de Zeeuw, Tomokazu Nunoue, Motofumi Sasaki, Kei Fujimoto, Shinji Kamei, Masao Toyoda, Satoshi Miyamoto, Munehiro Kitada, Kota Sakamoto, Takashi Wada, Kenichi Shikata, Daiji Kawanami, Akihiko Nakamura, Daisuke Suzuki, Tohru Nakamura, Hiromi Kuramoto, Takashi Hatanaka, Michihiro Yoshida
article en
7 citations

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/1.73m<sup>2</sup> 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 m<sup>2</sup> 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.

Kidney InternationalVol. 106(5)
Kanazawa University (JP), Tokai University (JP), University Medical Center Groningen (NL), Suzuki (Japan) (JP), Kanazawa Medical University (JP), University of Groningen (NL), Kagawa University (JP), University of Kochi (JP), Fukuoka University (JP), Inoue Hospital (JP), Kurashiki Central Hospital (JP), Okayama University Hospital (JP), Kamiichi General Hospital (JP), Okayama Prefecture (JP), Matsudo City Hospital (JP), Fukuyama Cardiovascular Hospital (JP), National Hospital Organization (JP), Jikei University Kashiwa hospital (JP), Okayama Saiseikai General Hospital (JP), Sumitomo Besshi Hospital (JP), Okayama Medical Center (JP), National Hospital Organization Takamatsu Medical Center (JP), Onomichi General Hospital (JP), Tohoku Medical and Pharmaceutical University (JP)
Mitsubishi Tanabe Pharma Corporation
Openalex Percentile: Top 9%
Diabetes Treatment and Management
2.50
DOIOpen Access PDFOpenAlex
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