Sodium-Glucose Cotransporter 2 Inhibitors in Kidney Diseases Other Than That Due to Diabetes: Benefits in Composite Renal Outcomes Driven by Immunoglobulin A Nephropathy.

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a well-established treatment for managing diabetic kidney disease (DKD). Clinical trials, including DAPA-CKD and EMPA-KIDNEY, indicate that these drugs are probably protective for the kidneys even in cases of chronic kidney disease (CKD) without diabetes, and secondary analysis of trials suggests that the overall outcome may be driven by the benefits of IgA nephropathy (IgAN). We aimed to evaluate whether benefits in composite renal outcomes in CKD, other than those due to diabetes, are observed beyond those with IgA nephropathy.

Methods: Data were extracted from the clinical trials DAPA-CKD and EMPA-KIDNEY, including patients with and without diabetes and CKD. Kidney diseases were classified as hypertensive/renovascular nephropathy or glomerular diseases, further subdivided into IgAN, focal segmental glomerulosclerosis (FSGS), and other glomerulonephritis. The heterogeneous group labeled as other/unknown was excluded from all analyses. The composite renal outcome was analyzed from pooled data using the Mantel-Haenszel risk ratio with a random-effects model and analyzed for all groups and then reanalyzed excluding the IgAN subgroup.

Results: The first pooled analysis, including all groups, demonstrated a 22% reduction in composite renal outcomes (RR 0.78, 95% CI 0.63-0.96, p = 0.02). However, when the IgAN group was excluded, the analysis revealed that the renoprotective benefits were no longer significant (RR 0.84, 95% CI 0.67-1.04, p = 0.11).

Conclusion: The overall benefit of SGLT2i in CKD due to causes other than diabetes, in patients with or without diabetes, may be predominantly driven by the benefits of IgAN.