New and Emerging Nonimmunosuppressive Drug Therapies for Primary Adult Glomerular Diseases

Primary adult glomerular diseases (GD) including IgA nephropathy (IgAN), membranous nephropathy, and focal segmental glomerulosclerosis, are important causes of chronic kidney disease, and may progress to kidney failure.Non-immunosuppressive foundation drug therapy for primary adult GD focuses on renin-angiotensin-aldosterone system (RAAS) inhibition to reduce proteinuria, alleviate hypertension, and reduce the risk of kidney disease progression.Additional agents with a distinct mechanism of action may be added or substituted in patients with a high progression risk or who are intolerant to RAAS inhibitors.This review highlights the role of lifestyle optimization as well as summarizing the currently non-immunosuppressive pharmacologic treatment options, for the management of primary adult GDs.We also provide an overview of the key pathophysiologic processes contributing to disease progression.Given the safety concerns associated with immunosuppressive therapies, we discuss the future role of newer non-immunosuppressive agents including finerenone (a non-steroidal mineralocorticoid receptor antagonist), sparsentan (a dual endothelin-angiotensin II receptor antagonist), atrasentan (an endothelin receptor antagonist), and iptacopan (complement inhibitor), which are currently FDA approved or are under investigation in clinical trials for primary GDs.These and other agents may expand the currently limited treatment landscape for patients with primary adult GD.