Abstract

Chronic kidney disease (CKD) is an increasingly prevalent pathological condition. The global rise in the number of individuals affected by CKD is dependent on the ageing, as well as on the growing prevalence of obesity, diabetes and hypertension. The need for treatment strategies aimed at preventing the onset of CKD and slowing its progression has led to the implementation of combination therapy, consisting of a Renin-Angiotensin-Aldosterone System inhibitor (RAASi) and a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), which has demonstrated efficacy in slowing CKD progression and reducing the occurrence of cardiovascular events. Updated guidelines recommend a tailored, multi-drug approach based on the residual cardiorenal risk of the individual patient. The KDIGO guidelines advocate for a stepwise approach in managing diabetes mellitus and CKD, with RAASi and SGLT-2i as first-line therapy, and GLP-1 receptor agonists (GLP-1 RA) and non-steroidal mineralocorticoid receptor antagonists (MRAs) as additional agents for further cardiorenal protection. Endothelin Receptor Antagonists (ERAs), a newer class of drugs, have shown antiproteinuric and nephroprotective effects in various trials. The objective of developing increasingly effective and personalized therapeutic strategies underscores the need to combine multiple drug classes that can act synergistically on different pathways.

Keywords: CKD, proteinuria, cardiovascular risk, diabetes mellitus, RAASi, SGLT-2i, MRAs, GLP-1 RA, ERAs