Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For?
Niralee Patel, Judy Hindi, Samira Farouk
Abstract
In recent robust randomized control trials (RCTs), sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) have been shown to dramatically decrease both kidney and cardiovascular (CV) adverse outcomes in patients with diabetic kidney disease, nondiabetic proteinuric kidney disease, and heart failure with reduced ejection fraction—with and without the presence of diabetes (1–6). For decades, both the nephrologist’s and transplant nephrologist’s arsenal for the management of proteinuric kidney disease has been limited to renin-angiotensin-aldosterone system blockade (7). Although SGLT2 inhibitors have taken the nephrology community by storm, patients with kidney transplants (KTs) have been notably excluded from large RCTs (8–10). Pathophysiologically, it seems likely they would also benefit from these apparent wonder drugs, particularly as many patients with KT have proteinuric kidney disease or heart failure. Similar to patients with native kidney disease, CV mortality is the leading cause of death in the KT population (11). Is it time to allow patients with KT to benefit from proposed SGLT2 inhibitor mechanisms, including tubuloglomerular feedback restoration, decreased inflammation and fibrosis, and alteration in energy metabolism, that all culminate in improved CV and kidney outcomes (12)? Here, we review the available data for SGLT2 inhibitor use in patients with KTs and discuss potential benefits and risk of their use in this population. Since 2015, sequential RCTs have demonstrated efficacy of SGLT2 inhibitors in improving both kidney and CV outcomes. A 2020 meta-analysis included six of these RCTs that studied SGLT2 inhibitor use (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) in close to 47,000 patients with diabetes (2). In all of the studies included in the meta-analysis, SGLT2 inhibitor use led to a reduction in heart failure hospitalizations, with empagliflozin being the only drug with significant CV death risk reduction. A reduction in kidney outcomes was seen with all agents …