Chronic kidney disease: a new look at pathogenetic mechanisms and treatment options

Area of Science:

• Nephrology
• Pathophysiology
• Pharmacology

Background:

• Chronic kidney disease (CKD) progression is linked to glomerular hyperfiltration, hypertension, and proteinuria.
• Proteinuria is increasingly recognized as a pathological and etiological factor in CKD, not merely a symptom.
• CKD pathophysiology involves proinflammatory and profibrotic signaling pathways, particularly in proximal tubular epithelial cells.

Purpose of the Study:

• To review experimental and clinical evidence for novel drug treatments targeting CKD progression.
• To explore common therapeutic targets for diverse kidney diseases based on shared pathomechanistic pathways.
• To assess the potential of emerging renoprotective strategies.

Main Methods:

• Review of preclinical and clinical studies on prospective CKD treatments.
• Analysis of animal models of kidney disease (obstructive uropathy, glomerulonephritis).
• Examination of signaling pathways involved in progressive proteinuric CKD.

Main Results:

• Common proinflammatory and profibrotic pathways are activated in progressive proteinuric CKD across various models.
• Several prospective drug treatments show conceptual promise for renoprotection.
• Definitive clinical evidence is lacking for many novel treatments, and some have significant adverse effects.

Conclusions:

• Proteinuria plays a critical role in CKD progression via inflammatory and fibrotic mechanisms.
• Shared pathomechanisms suggest potential for common therapeutic targets in a wide range of kidney diseases.
• Further clinical studies are essential to validate new renoprotective treatments and guide recommendations.