Bis(monoacylglycero)phosphate (BMP), also known as
lysobisphosphatidic acid (LBPA), is a
phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible
biomarker of disorders such as genetic
lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this
biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific
lipid in biofluids. The present study demonstrates that in absence of any sign of
renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the
antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with
amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV
protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary
biomarker of
amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar
lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new
lipid marker of urinary exosomes.