Heart failure (HF) is a major public health concern worldwide. The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid-range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on the European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology.

Purpose: The peptidomes of spent hemodialysate, urine, and plasma are investigated, to shed light on peptide handling in the kidney. Experimental Design: Fifteen plasma, 15 urine, and 13 spent hemodialysate samples are collected from age-and sex-matched subjects with chronic kidney disease. Peptide identification and quantification are performed with capillary electrophoresis-coupled mass spectrometry. Results: A total of 6278 urinary peptides, 1743 plasma peptides, and 1727 peptides from spent hemodialysate are detected. Of these, sequences can be assigned to 1580, 419, and 352 peptides, respectively. A strong correlation in peptide abundance between urine and spent hemodialysate (p = 3 × 10 −21 , Rho = 0.52), a moderately strong correlation between spent hemodialysate and plasma (p = 4.5 × 10 −5 , Rho = 0.30), and no significant correlation between urine and plasma (p = 0.11, Rho = 0.094) are found. Collagen and fibrinogen alpha peptides are highly abundant in all three body fluids. In spent hemodialysate, thymosin ß4 is one of the most abundant peptides, which is shown to be negatively associated with the estimated glomerular filtration rate (Rho = −0.39, p-value = 3.9 × 10 −81). Conclusion and Clinical Relevance: The correlation of peptide abundance in these three body fluids is lower than expected, supporting the hypothesis that tubular reabsorption has a major impact on urinary peptide content. Further investigation of thymosin ß4 in hemodialysis is thus warranted.