Current Use and Complementary Value of Combining in Vivo Imaging Modalities to Understand the Renoprotective Effects of Sodium-Glucose Cotransporter-2 Inhibitors at a Tissue Level

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed to treat diabetes and have been shown to improve renal and cardiovascular outcomes in patients with- but also without diabetes. The mechanisms underlying these beneficial effects are incompletely understood, as is the response variability between- and within patients. Imaging modalities allow in vivo quantitative assessment of physiological, pathophysiological, and pharmacological processes at kidney tissue level and are therefore increasingly being used in nephrology. They provide unique insights into the renoprotective effects of SGLT2i and the variability in response and may thus contribute to improved treatment of the individual patient. In this mini-review, we highlight current work and opportunities of renal imaging modalities to assess renal oxygenation and hypoxia, fibrosis as well as interaction between SGLT2i and their transporters. Although every modality allows quantitative assessment of particular parameters of interest, we conclude that especially the complementary value of combining imaging modalities in a single clinical trial aids in an integrated understanding of the pharmacology of SGLT2i and their response variability.

Feasibility Study to Assess Canagliflozin Distribution and Sodium‐Glucose Co‐Transporter 2 Occupancy Using [18F]Canagliflozin in Patients with Type 2 Diabetes

“…Imaging modalities might contribute to this understanding as they allow in vivo quantitative assessment of physiological, pathophysiological, and pharmacological processes at the (kidney) tissue level and are therefore increasingly used in nephrology. They provide unique insights into the nephroprotective effects of SGLT2 inhibitors and the variability in response 9 . To quantitatively and use minimal invasive methods to investigate the tissue distribution of SGLT2 inhibitors and SGLT2 density in patients, we previously developed a good manufacturing practice automated synthesis method for the 18 F‐isotopologue of the extensively characterized, selective SGLT2 inhibitor canagliflozin, which thus shares its toxicological and pharmacological characteristics, enabling its immediate use in patients 10 …”

“…They provide unique insights into the nephroprotective effects of SGLT2 inhibitors and the variability in response. 9 To quantitatively and use minimal invasive methods to investigate the tissue distribution of SGLT2 inhibitors and SGLT2 density in patients, we previously developed a good manufacturing practice automated synthesis method for the 18 F-isotopologue of the extensively characterized, selective SGLT2 inhibitor canagliflozin, which thus shares its toxicological and pharmacological characteristics, enabling its immediate use in patients. 10 We hypothesize that the underlying mechanisms of the varying response in multiple parameters within an individual can be attributed to variability in the causal path among drug administration, plasma exposure, drug tissue distribution, and tissue receptor interaction.…”