Homocitrulline as marker of protein carbamylation in hemodialyzed patients.
BACKGROUND
Homocitrulline (HCit) is a carbamylation-derived product (CDP) that has been identified as a valuable biomarker of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of this study was to determine whether initiation of hemodialysis therapy (HD) could induce variations of HCit concentrations in CKD patients.


METHODS
Serum HCit concentrations were determined by LC-MS/MS in CKD patients (n=108) just before (M0) and six months (M6) after the initiation of HD therapy.


RESULTS
Mean HCit concentrations reached 1000μmol/mol Lysine before initiation of HD therapy and decreased by 50% within 6months after HD onset. HCit concentrations remained stable over time as assessed during a 24-months follow-up period. HCit was mostly found in its protein-bound form in HD patients. HCit concentrations obtained at M0 were positively correlated with urea (r=0.58) and carbamylated hemoglobin (r=0.41), and are likely to be promising predictive markers of mortality. However, no correlations were found between HCit concentrations and Kt/V values, suggesting that HCit is not a marker of HD efficiency.


CONCLUSIONS
HCit concentrations reflect the intensity of protein carbamylation and are stable over time during HD treatment, making HCit a reliable biomarker in the follow-up of CKD patients.
University Hospital of Reims, Maison Blanche Hospital, Laboratory of Paediatric Biology and Research, Reims, France; University of Reims Champagne-Ardenne, "Extracellular Matrix and Cell Dynamics" (MEDyC) Research Unit UMR CNRS No 7369, Reims, France. Electronic address: sjaisson@chu-reims.fr.
Stéphane
S
Jaisson
University Hospital of Reims, Nephrology Department, Reims, France.
Isabelle
I
Kazes
University Hospital of Reims, Maison Blanche Hospital, Laboratory of Paediatric Biology and Research, Reims, France; University of Reims Champagne-Ardenne, "Extracellular Matrix and Cell Dynamics" (MEDyC) Research Unit UMR CNRS No 7369, Reims, France.
Aurore
A
Desmons
University Hospital of Reims, Nephrology Department, Reims, France.
Fouad
F
Fadel
University Hospital of Reims, Maison Blanche Hospital, Laboratory of Paediatric Biology and Research, Reims, France; University of Reims Champagne-Ardenne, "Extracellular Matrix and Cell Dynamics" (MEDyC) Research Unit UMR CNRS No 7369, Reims, France.
Jean-Baptiste
JB
Oudart
University Hospital of Reims, Maison Blanche Hospital, Laboratory of Paediatric Biology and Research, Reims, France.
Izabella C R Dos
IC
Santos-Weiss
University Hospital of Reims, Department of Pharmacology, Reims, France.
Hervé
H
Millart
University of Reims Champagne-Ardenne, "Extracellular Matrix and Cell Dynamics" (MEDyC) Research Unit UMR CNRS No 7369, Reims, France; University Hospital of Reims, Nephrology Department, Reims, France.
Fatouma
F
Touré
University of Reims Champagne-Ardenne, "Extracellular Matrix and Cell Dynamics" (MEDyC) Research Unit UMR CNRS No 7369, Reims, France; University Hospital of Reims, Nephrology Department, Reims, France.
Philippe
P
Rieu
University Hospital of Reims, Maison Blanche Hospital, Laboratory of Paediatric Biology and Research, Reims, France; University of Reims Champagne-Ardenne, "Extracellular Matrix and Cell Dynamics" (MEDyC) Research Unit UMR CNRS No 7369, Reims, France.
Philippe
P
Gillery
D015415:Biomarkers / Q000097:blood; D002219:Carbamates / Q000378:metabolism*; D002956:Citrulline / Q000031:analogs & derivatives* / Q000097:blood; D006441:Hemoglobin A / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D008137:Longitudinal Studies; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; D002219:Carbamates; C001352:homocitrulline; D002956:Citrulline; C022017:hemoglobin A, carbamylated; D006441:Hemoglobin A
Biomarker; Carbamylation; End-stage renal disease; Hemodialysis; Homocitrulline