Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis...

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Biochemistry

Background:

• Protein-bound uremic toxins are established cardiovascular (CV) risk factors in end-stage renal disease patients.
• Indole-3-acetic acid (IAA), a uremic toxin, is linked to CV disease, but its precise role is unclear.
• Mitogen-activated protein kinase (MAPK) signaling pathways are implicated in CV disease pathogenesis.

Purpose of the Study:

• To investigate the association between circulating Indole-3-acetic acid (IAA) levels and proteins within the MAPK signaling cascade in hemodialysis (HD) patients.
• To explore potential pathophysiological mechanisms linking IAA to cardiovascular disease in kidney disease patients.

Main Methods:

• Quantification of circulating total form IAA using mass spectrometry.
• Measurement of forty MAPK cascade-associated proteins via proximity extension assay in 331 prevalent HD patients.
• Multivariable-adjusted linear regression models and bioinformatics analysis (STITCH tool).

Main Results:

• Circulating IAA levels showed a significant positive association with stem cell factor (SCF) (β = 0.13, p = 0.004) after adjusting for multiple testing.
• Bioinformatics analysis suggested IAA's involvement in regulating cell proliferation, hematopoietic cells, and the JAK-STAT signaling pathway.
• These findings highlight a potential novel mechanistic link between IAA and cardiovascular risk.

Conclusions:

• Circulating IAA levels are associated with stem cell factor in hemodialysis patients, suggesting a novel pathway contributing to cardiovascular risk.
• The findings provide insights into non-traditional cardiovascular risk factors in kidney disease.
• Further in vitro studies are warranted to validate the identified mechanistic pathways.