Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach

Abstract

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium-glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease.

Keywords: ACEi; ARBs; CKD; GLP-1; SGLT2i; finerenone; proteinuria; sparsentan.

Figure 1

Management of proteinuria. Legend: ACEis, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; SGLT2i, sodium–glucose cotransporter 2 inhibitors; GLP-1RA, GLP-1 receptor agonists.