Plasma and Urinary Amino Acid Metabolomic Profiling in Patients with Different Levels of Kidney Function

Abstract

SummaryBackground and objectives 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.Design, setting, participants, & measurements 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: 35.9616.3 versus 61.8623.6 mmol/L, P,0.01; in urine: 1.061.2 versus 7.1614.3 mmol/mol creatinine, P,0.001). Plasma asymmetric dimethylarginine levels were higher in advanced CKD (CKD stages 2 and 3, 0.5760.29; CKD stages 4 and 5, 1.0260.48, P,0.001), whereas urinary excretion was lower (2.3760.93 versus 1.5161.43, 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).Conclusion 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.

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“…The inverse association between eGFR and l-citrulline in most of the groups also confirms previous findings which suggested this link by indicating increased plasma l-citrulline levels in patients with different degrees of chronic kidney disease (Lau et al 2000;Duranton et al 2013). Our finding of a negative association between eGFR and SDMA in whites, is also in agreement with the literature as summarized in a meta-analysis (Kielstein et al 2006), but it is unclear why this relationship was absent in the blacks.…”

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“…The elevation of serum AFMK may indicate enhanced oxidative stress in HD patients. For the serum biomarkers, the increased levels of proline and citrulline and decreased levels of arginine, glutamine, lysine, and tryptophan reflected the disturbance of the serum amino acid profile in HD patients, which has been reported previously [32].…”

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