Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences

Area of Science:

• Nephrology
• Pathology
• Molecular Biology

Background:

• Fibrosis involves excessive extracellular matrix accumulation after tissue injury, potentially leading to organ dysfunction.
• Pathological fibrosis becomes an irreversible, self-maintained process, significantly impacting organs.
• Chronic kidney disease (CKD) is associated with significant pathological fibrosis affecting kidney and cardiac function.

Purpose of the Study:

• To review key systems, molecules, and responses driving pathological fibrosis in CKD.
• To highlight the roles of specific factors in CKD-related fibrosis.
• To emphasize the negative kidney and cardiac impact of these fibrotic pathways.

Main Methods:

• Review of existing literature on fibrosis pathogenesis in CKD.
• Focus on molecular and systemic pathways involved in fibrosis.
• Analysis of the interplay between inflammation, hormonal systems, and growth factors in CKD.

Main Results:

• Identified inflammation, renin-angiotensin system (RAS), parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, microRNAs (miRs), and the vitamin D hormonal system as key drivers of fibrosis in CKD.
• These factors are integral to core and regulatory pathways promoting pathological fibrosis.
• These pathways exert a substantial negative impact on kidney and cardiac health in CKD patients.

Conclusions:

• Multiple interconnected pathways, including inflammation and hormonal systems, critically drive pathological fibrosis in CKD.
• Understanding these fibrotic mechanisms is crucial for addressing the significant kidney and cardiac morbidity in CKD.
• Targeting these pathways may offer therapeutic strategies to mitigate fibrosis progression and its consequences in CKD.