SGLT2 inhibitors help to improve kidney function in patients with chronic kidney disease (CKD) and are promising for IgA nephropathy (IgAN), although they remain under investigation. Studies evaluating the potential use of SGLT2 inhibitors in patients with IgAN were discussed at the recent Kidney Week meeting.

Following these proceedings, featured expert Sayna Norouzi, MD, FASN, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis. Dr Norouzi’s clinical perspectives are presented here.

SGLT2 inhibitors play a multifactorial role in modifying the pathophysiology of CKD. They activate the tubuloglomerular feedback mechanism, which reduces persistent glomerular hyperfiltration and intraglomerular pressure to help prevent further damage to the kidneys and improve renal hemodynamics. SGLT2 inhibitors may be helpful in the setting of IgAN because they reduce proteinuria, and a reduction in proteinuria has been linked to better outcomes for patients with IgAN.

There have been studies evaluating the use of SGLT2 inhibitors in IgAN. For example, the placebo-controlled DAPA-CKD trial examined dapagliflozin in patients with CKD and included individuals with IgAN. In an analysis published on the subset of patients with IgAN, those who received dapagliflozin had a reduction in proteinuria vs those who received placebo. One limitation of the DAPA-CKD trial that I think we have to pay attention to is that having biopsy-proven IgAN was not part of the inclusion criteria. If the patient had a previous biopsy indicating IgAN, they were able to enroll in this trial.

Patients enrolled in the PROTECT open-label extension substudy can receive SGLT2 inhibitors in combination with sparsentan, a DEARA with US Food and Drug Administration (FDA) approval for IgAN. Data from the substudy were presented at Kidney Week 2024 by Laura Kooienga, MD, and colleagues in a poster (abstract FR-PO851). The phase 2 SPARTACUS trial evaluated the combination of sparsentan with SGLT2 inhibitors in patients with IgAN. Isabelle Ayoub, MD, and colleagues presented results from an interim analysis of SPARTACUS in a poster at Kidney Week 2024 (abstract FR-PO849). I am really looking forward to the final results to see if adding SGLT2 inhibitors to sparsentan can actually magnify the results of sparsentan alone and if it can help to reduce proteinuria in a shorter amount of time.

I think it is important to note that the previous 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for IgAN said to start with optimized supportive care, which meant using RAAS inhibitors for at least 90 days and then considering disease-modifying drugs such as corticosteroids if the patient was not responding after the 90 days. In the recently released public review draft of the 2024 KDIGO guidelines for IgAN, it considers using SGLT2 inhibitors and RAAS inhibitors at the same time as disease-modifying medication, now that we have these newer medications, with less focus on corticosteroids. In my own practice, all of my patients who have IgAN are receiving a combination of RAAS inhibitors and SGLT2 inhibitors off-label.