Effect of fenofibrate treatment on the low molecular weight urinary proteome of healthy volunteers

Abstract

Purpose: Urinary peptidome changes and discrimination for potential renal glomerular and tubular damage after 6 wk of fenofibrate treatment were evaluated in 26 healthy subjects.

Experimental design: Peptide profiling was performed in urine samples before and after treatment using high-resolution capillary electrophoresis coupled with electrospray ionization mass spectrometry.

Results: A panel of 88 fenofibrate-sensitive peptides was detected with a frequency of ≥50% before and after treatment. This was reduced to 36 peptides by repeating the comparison ten times by randomly excluding samples at each time-point. Nineteen peptides were consistent and reliable biomarkers after an additional comparison with an age and sex-matched subject control group. Levels of peptides identified as fragments of Collagen α-1 (I), Collagen α-1 (XVII), Collagen α-2 (VIII) or sodium/potassium-transporting ATPase subunit gamma were reduced after fenofibrate treatment. Classification scores for renal tubular and glomerular damages determined by support vector machine based biomarker models increased after treatment but remained below pathological score cutoff values.

Conclusions and clinical relevance: Fenofibrate treatment led to minor modifications of the urinary proteomic profile in a way that does not create safety issues affecting glomerular and tubular functions. Urinary peptide profiling proved to be appropriate to monitor drug pharmacological effects in a clinical setting.