Addressing Proteinuria in Patients with Immunoglobulin A Nephropathy Through Concomitant Use of Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors

IgA nephropathy (IgAN) can impact life expectancy in those affected, thus efficacious treatment is key. Endothelin 1 (ET-1) and angiotensin II (Ang II) are instrumental in the development of IgAN-associated renal damage. Use of sparsentan, a dual ET Type A receptor (ETAR) and Ang II subtype 1 receptor (AT1R) antagonist (DEARA), can lead to reductions in proteinuria and thereby help to slow kidney function decline in patients with IgAN. Sparsentan is included in the 2024 draft Kidney Disease Improving Global Outcome (KDIGO) guidelines for patients with IgAN at risk of progressive kidney function loss. Additionally, other KDIGO guidelines recommend a sodium-glucose cotransporter-2 inhibitor (SGLT2i) for all adults at risk of chronic kidney disease (CKD) progression as they are associated with reductions in both kidney and cardiac morbidity and mortality risks. If needed, there is the potential to combine these drugs. Studies regarding such use were presented in three posters at the American Society of Nephrology’s (ASN) Kidney Week 2024. The first included updated interim findings from the open label extension (OLE) study of the Phase III PROTECT trial of sparsentan in a subset of participants where an SGLT2i had been added at the investigators’ discretion. Here, SGLT2i addition led to further proteinuria reduction. The second poster detailed a prespecified interim analysis of the SPARTACUS trial wherein participants with IgAN receiving an SGLT2i and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) treatment were switched to sparsentan plus an SGLT2i. Such a regimen led to proteinuria reduction from baseline. In the final poster, including four patients with IgAN in tertiary care, the concomitant use of sparsentan with an SGLT2i led to proteinuria reduction in the real-world setting regardless of proteinuria levels or kidney function at sparsentan initiation. Taken together, these studies suggest the utility of concomitant use of sparsentan with an SGLT2i in patients at risk of kidney failure progression.