While renin-angiotensin system (RAS) blockers (e.g., angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB)) and sodium-glucose co-transporters-2 inhibitors (SGLT2i) have shown beneficial renal and CV effects in DKD patients by targeting hemodynamic and metabolic drivers of CKD progression (35–40), they inadequately address the inflammation and fibrosis driven by MR overactivation, leading to a persistent high residual risk of CKD progression and CV events development, even in response to combined treatment by these two therapies (9, 13, 37, 38, 41). The gene discussed is ACE; the disease is chronic kidney disease.