Nicotinamide Attenuates Complement and Coagulation Pathways and Resultant Renal Fibrosis

Area of Science:

• Nephrology
• Immunology
• Hematology

Background:

• Coagulation and complement pathways interact, influencing inflammation and thrombosis.
• Their specific roles in chronic kidney disease (CKD) pathogenesis are not fully understood.

Purpose of the Study:

• To investigate the association between coagulation and complement systems in CKD.
• To explore the therapeutic potential of nicotinamide (NAM) in modulating these pathways in CKD.

Main Methods:

• Analysis of CKD patient cohorts for coagulation markers (fibrinogen, prothrombin time) and complement levels (C3, C4).
• Gene expression analysis in CKD renal tissues and adenine/folic acid-induced nephropathy mouse models.
• RNA sequencing and KEGG pathway analysis to evaluate NAM's effects on coagulation and complement cascades.

Main Results:

• Elevated fibrinogen and shortened prothrombin time correlated with higher C3 and C4 levels in CKD patients.
• Upregulation of coagulation factors (tissue factor, fibrinogen) and C3 observed in fibrotic kidneys of mouse models.
• NAM administration significantly inhibited coagulation and complement cascades in adenine-induced nephropathy, suppressing inflammasome and neutrophil extracellular trap formation.

Conclusions:

• Excessive coagulation and complement activation are implicated in CKD pathogenesis.
• Nicotinamide (NAM) demonstrates therapeutic potential by modulating these pro-thrombotic and inflammatory pathways in CKD.