Currently, a major focus in glomerular disease is on slowing the progression to prevent end-stage kidney disease, and the combination of SGLT2 inhibitors and RAAS blockade may help to achieve this goal. Updates on glomerular disease, including with regard to the use of SGLT2 inhibitors, were presented at the National Kidney Foundation (NKF) 2024 Spring Clinical Meetings (SCM24).

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

There has been a lot of research over the last few years looking at therapies that might help prevent nephron loss in the setting of chronic kidney disease (CKD). In particular, SGLT2 inhibitors have been extensively studied in diabetic nephropathy to help slow the rate of kidney function decline, prevent kidney failure, and reduce proteinuria.

Recently, 2 large trials studied SGLT2 inhibitors in CKD, and a large proportion of patients in these trials had some form of glomerular disease. The DAPA-CKD trial and, more recently, the EMPA-KIDNEY trial found that the addition of an SGLT2 inhibitor to RAAS inhibitor therapy significantly reduced proteinuria, better preserved glomerular filtration rate, and delayed the progression of CKD in patients with diabetic and nondiabetic kidney disease (ie, IgA nephropathy or other forms of glomerular disease). I think that there is a general consensus among the community that RAAS blockade and an SGLT2 inhibitor are a standard of care to slow the progression of CKD in some patients.

A retrospective chart review looking at SGLT2 inhibitors in 2074 patients with nondialysis CKD was presented at SCM24 (poster 370). From 2021 to 2023, the percentage of patients with nondialysis CKD who were treated with an SGLT2 inhibitor more than doubled, from 17% to 38%, which is dramatic. In this study, nearly 50% of patients who had a primary glomerular disease such as IgA nephropathy, focal segmental glomerulosclerosis, and C3 glomerulopathy were treated with an SGLT2 inhibitor as of 2023. Of the 551 responding nephrologists, 82% agreed that SGLT2 inhibitors may significantly slow the progression of CKD in patients with glomerular disease. So, there is a great deal of excitement regarding SGLT2 inhibitors, and that excitement is translating into more and more nephrologists prescribing them to help slow the progression of CKD.

There has also been a lot of research over the last 5 to 10 years examining the risk for CKD among patients of African ancestry. These patients seem to have a higher risk for progressive kidney disease and for kidney disease with more resistance to therapy no matter what the disease is.

In addition, genetic variation in APOL1 is present in some patients with African ancestry. The idea is that the genetic variations in APOL1 evolved over time to protect against trypanosome infection. However, it seems that patients who have a homozygous mutation for APOL1 tend to be at higher risk for developing early and progressive CKD, and this was discussed at SCM24 during a glomerular disease preconference course. An ongoing phase 3 clinical trial is evaluating an agent that targets APOL1. So, that has been an exciting development over the last couple of years. It will be very interesting to see how that study turns out because this is a high-risk population for whom we have not had many treatments. We are very hopeful that targeting APOL1 may help slow the progression of kidney disease.