Promoting soluble guanylate cyclase activity via guanylate cyclase stimulators or guanylate cyclase activators: a feasible option in diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is a word-wide problem. In patients with diabetes mellitus (DM), DKD occurs in up to 40% of patients and is the most common cause of chronic kidney disease (CKD) in diabetic patients. Despite various reno-protective agents, DKD still progresses in the majority of patients necessitating further novel therapeutic options. Recently, another class of medications working by augmenting soluble guanylate cyclase (sGC) has been studied in DKD. Soluble guanylate cyclase activity can be increased by 2 classes of medications with different modes of action, namely sGC stimulators and sGC activators. Preclinical and clinical studies have shown that these medications may reduce albuminuria/proteinuria independent of BP lowering, decrease inflammation, reduce oxidative stress and kidney fibrosis, and have favorable impacts on lipid profile and glucose levels. Importantly, these medications can be used with other kidney protective agents such as Renin-angiotensin system inhibitors and Sodium-glucose cotransporter-2 inhibitors. In this review, we summarized the experimental and clinical studies specifically investigating the effects of sGC stimulators and sGC activators in the context of DKD. Additionally, we explore the effects of increasing sGC on laboratory and clinical parameters in DKD. We also identify knowledge gaps and proposals for future studies.