Suggestions for Successful SGLT2i Use in Glomerular Disease

Abstract and Introduction

Abstract

Purpose of Review: Recent advances in the world of glomerular diseases have largely focussed on remission induction with immune modulating therapy. It is well recognised that even with the best available treatments, patients with glomerular diseases may have an increased risk of progressive renal and cardiovascular disease.

Recent Findings: The arrival of large trials looking at the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with chronic kidney disease (CKD) and diabetes or not has shifted the entire focus of current management and the shift needs to go further. This review summarises the background to these landmark trials and provides practical guidance for implementation of the results in a general nephrology clinic. In sub-group analyses of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) clinical trial, SGLT2i improved renal outcomes in patients with immunoglobulin A (IgA) nephropathy highlighting the potential for this drug class in glomerular disease. We also discuss where the gaps in evidence are and where future trials in glomerular diseases, be they primary or secondary, should be focussed.

Summary: The renal community has never before had evidence of this strength upon which to base recommendations for patients with CKD and we should be grasping it with both hands.

Introduction

Glomerular disease management is historically focused on renoprotection through blood pressure reduction,^[1] renin-angiotensin system (RAS) inhibition^[1–3] and, where appropriate, immunomodulation.^[4] The incremental increase in mortality risk associated with both chronic kidney disease (CKD) and nephrotic syndrome has been clearly described^[5,6] but remains poorly mitigated. Clinical trial design has been hampered by the opinion that hard endpoints, such as end stage kidney disease or 40% decline in eGFR or death, were unachievable in a clinical trial timeframe, and alternatives were sought.^[7] The recent publication of landmark trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has completely changed the landscape of future trials in the management of glomerular disease – both primary and secondary. This review focuses on the mechanisms of action of these medicines, their current role, how to safely adopt them in clinic and where the gaps in evidence now lie.