Therapeutic approaches in the management of chronic kidney disease: the past, the present, and the future.

Abstract

Chronic kidney disease (CKD) remains a major global health burden, contributing significantly to morbidity, mortality, and healthcare costs. Over the past century, therapeutic approaches to CKD have evolved substantially, reflecting advances in the understanding of renal pathophysiology. Early strategies centered around dietary interventions, notably low-protein diets, aimed at mitigating the progression of renal impairment. Subsequently, rigorous blood pressure control and the introduction of renin-angiotensin-aldosterone system (RAAS) blockade with ACE inhibitors and ARBs markedly improved renal outcomes. In the modern era, the emergence of sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (nsMRAs) such as finerenone, and glucagon-like peptide-1 receptor agonists (GLP-1RAs) has redefined the therapeutic landscape, offering robust cardiorenal protection. Despite these advances, CKD often remains a progressive disease, underscoring the need for continued innovation. Future therapeutic strategies, including aldosterone synthase inhibitors, soluble guanylate cyclase activators, and therapies currently in preclinical development - such as gene-editing technologies, novel peptide therapies, and renal regenerative approaches - aim to target the fundamental drivers of CKD progression. These emerging modalities hold the promise not merely of slowing disease progression but potentially restoring renal function. As the field moves toward personalized, mechanism-based interventions, early diagnosis and prompt initiation of therapy will remain pivotal. This review traces the historical evolution of CKD management, highlights contemporary advances, and explores the exciting horizon of future therapeutic opportunities.