Canagliflozin Effective in Slowing Kidney Function Decline in Early-Stage CKD, reveals research

A recent study published in the Kidney International found that the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin may significantly slow chronic kidney disease (CKD) progression in individuals with type 2 diabetes and microalbuminuria. The CANPIONE trial investigated the efficacy of this drug in patients with early-stage CKD. It focused on the decline of kidney function measured with the help of estimated glomerular filtration rate (eGFR) slope, as well as changes in albuminuria levels.

The study included the participants with type 2 diabetes who had a urinary albumin-to-creatinine ratio (UACR) between 50 to 300 mg/g and an eGFR of at least 45 ml/min/1.73m² which signifies early-stage CKD. A total of 98 participants were randomly assigned to either receive canagliflozin or a guideline-recommended treatment excluding SGLT2 inhibitors, where 96 participants ultimately received at least one treatment dose.

The results showed a significantly greater reduction in UACR in the canagliflozin group when compared to the control group. Also, the least-squares mean change from baseline in the geometric mean UACR was 30.8% lower in the canagliflozin group which was a marked improvement over the control group. This highlighted the potential of canagliflozin in reducing albuminuria.

The eGFR slope change measured how the the kidney function of participants declined before and during treatment. A steeper slope indicates faster kidney function deterioration, while a slower slope suggests protective effects on the kidneys. The difference in eGFR slope between the canagliflozin and control groups was significant in this trial. The participants in the canagliflozin group had a 4.4 ml/min/1.73 m² per year slower decline in eGFR which demonstrated the protective effect of this drug on kidney function. This effect was even more pronounced in individuals who initially expressed a more rapid decline in eGFR which suggests the potential benefits of canagliflozin in patients at higher risk of disease progression.

The CANPIONE trial suggests that measuring the change in eGFR slope within individuals could be a novel method for evaluating the kidney-protective potential of new therapies in the early stages of CKD. Overall, the results also illuminate the potential for SGLT2 inhibitors like canagliflozin to be incorporated into early intervention strategies for CKD in patients with type 2 diabetes by potentially altering the course of the disease and improving long-term outcomes.

Reference:

Miyamoto, S., Heerspink, H. J. L., de Zeeuw, D., Sakamoto, K., Yoshida, M., Toyoda, M., Suzuki, D., Hatanaka, T., Nakamura, T., Kamei, S., Murao, S., Hida, K., Ando, S., Akai, H., Takahashi, Y., Kitada, M., Sugano, H., Nunoue, T., Nakamura, A., … Shikata, K. (2024). A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope. In Kidney International. Elsevier BV. https://doi.org/10.1016/j.kint.2024.08.019