Plasma and urinary amino acid metabolomic profiling in patients with different levels of kidney function.
OBJECTIVE
Patients with CKD display altered plasma amino acid profiles. This study estimated the association between the estimated GFR and urinary and plasma amino acid profiles in CKD patients.


METHODS
Urine and plasma samples were taken from 52 patients with different stages of CKD, and plasma samples only were taken from 25 patients on maintenance hemodialysis. Metabolic profiling was performed by liquid chromatography coupled with tandem mass spectrometry after phenylisothiocyanate derivatization.


RESULTS
Most plasma amino acid concentrations were decreased in hemodialysis patients, whereas proline, citrulline, asparagine, asymmetric dimethylarginine, and hydroxykynurenine levels were increased (P<0.05). Both plasma levels and urinary excretion of citrulline were higher in the group of patients with advanced CKD (CKD stages 2 and 3 versus CKD stages 4 and 5; in plasma: 35.9±16.3 versus 61.8±23.6 µmol/L, P<0.01; in urine: 1.0±1.2 versus 7.1±14.3 µmol/mol creatinine, P<0.001). Plasma asymmetric dimethylarginine levels were higher in advanced CKD (CKD stages 2 and 3, 0.57±0.29; CKD stages 4 and 5, 1.02±0.48, P<0.001), whereas urinary excretion was lower (2.37±0.93 versus 1.51±1.43, P<0.001). Multivariate analyses adjusting on estimated GFR, serum albumin, proteinuria, and other covariates revealed associations between diabetes and plasma citrulline (P=0.02) and between serum sodium and plasma asymmetric dimethylarginine (P=0.03). Plasma tyrosine to phenylalanine and valine to glycine ratios were lower in advanced CKD stages (P<0.01).


CONCLUSIONS
CKD patients have altered plasma and urinary amino acid profiles that are not corrected by dialysis. Depending on solutes, elevated plasma levels were associated with increased or decreased urinary excretion, depicting situations of uremic retention (asymmetric dimethylarginine) or systemic overproduction (citrulline). These results give some insight in the CKD-associated modifications of amino acid metabolism, which may help improve their handling.
RD Néphrologie, Montpellier, France;, †BIOCRATES Life Sciences AG, Innsbruck, Austria;, ‡Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany;, §Centre Hospitalier Universitaire et Université Bordeaux II, Bordeaux, France;, ‖Néphrologie, Dialyse et Transplantation, Université de Montpellier, Hôpital Lapeyronie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France;, ¶Laboratoire de Recherche en Biostatistique, Epidemiologie et Recherche Clinique, Institut Universitaire de Recherche Clinique, Montpellier, France, *Néphrologie Dialyse St. Guilhem, Sète, France.
Flore
F
Duranton
Ulrika
U
Lundin
Nathalie
N
Gayrard
Harald
H
Mischak
Michel
M
Aparicio
Georges
G
Mourad
Jean-Pierre
JP
Daurès
Klaus M
KM
Weinberger
Angel
A
Argilés
D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood* / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016009:Chi-Square Distribution; D002853:Chromatography, Liquid; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy / Q000652:urine*; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
D000596:Amino Acids; D015415:Biomarkers