Early alterations of plasma free amino acids in chronic renal failure

Ceballos, I.; Chauveau, P; Guérin, Valérie; Bardet, J.; Parvy, P; Kamoun, P.; Jungers, Paul

doi:10.1016/0009-8981(90)90154-k

Cited by 99 publications

(75 citation statements)

References 26 publications

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“…Despite the fact that these preliminary results, such as the accumulation of fatty acids and the depletion of amino acids, were obtained from a relatively small-scale clinical study, the findings are rational and in good agreement with conventional studies that centered mainly on individual or certain metabolites [29][30][31]. Therefore, the proposed GC-MS-based metabolic profiling technology is able to characterize the metabolic disturbances associated with human uremia, and so it potentially provides a holistic therapeutic strategy for uremic patients.…”

Section: Clinical Applicationsupporting

confidence: 55%

GC-MS with ethyl chloroformate derivatization for comprehensive analysis of metabolites in serum and its application to human uremia

et al. 2008

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Abstract:An optimized method based on GC-MS with ethyl chloroformate derivatization has been developed for the comprehensive analysis of endogenous metabolites in serum. Twenty-two reference standards and serum samples were used to validate the proposed method. The correlation coefficient was higher than 0.9900 for each of the standards, and the LOD varied from 125 to 300 pg on-column. The analytical equipment exhibited good repeatability (RSD<10%) for all of the standards. Both the repeatability and the within-48-h stability of the analytical method were satisfactory (RSD<10%) for the 18 metabolites identified in the serum samples. Mean recovery was acceptable for the 18 metabolites, ranging from 70% to 120% with RSDs of less than 10%. Using the optimized protocol and a subsequent multivariate statistical technique, complete differentiation was achieved between the metabolic profile of uremic patients and that of age-and sex-matched normal subjects. Significantly decreased levels of valine, leucine, and isoleucine and increased levels of myristic acid and linoleic acid were observed in the patient group. This work demonstrated that this method is suitable for serumbased metabolic profiling studies.

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Section: Clinical Applicationsupporting

confidence: 55%

GC-MS with ethyl chloroformate derivatization for comprehensive analysis of metabolites in serum and its application to human uremia

et al. 2008

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“…Among 22 compounds, 13 compounds were already reported as uremic retention solutes. 5,[14][15][16][17][18][19][20][21][22][23][24] On the other hand, other nine cationic compounds, N-acetylglucosamine, g-butyrobetaine, ophthalmate, N-e-acetyllysine, cytosine, hypotaurine, 7-methylguanine, methionine sulfoxide and Asn, have not been reported to be accumulated (shaded in Table 2). …”

Section: Study Population and Ce-ms Analysismentioning

confidence: 99%

Metabolomic profiling of uremic solutes in CKD patients

et al. 2010

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Early detection and accurate monitoring of patients with chronic kidney disease (CKD) is likely to improve care and decrease the risk of cardiovascular and cerebrovascular diseases. As a new diagnostic tool, we examined the retention of uremic solutes as a simpler, more accurate method to assess renal function. To achieve this, we comprehensively evaluated these solutes in CKD patients. By capillary electrophoresis with mass spectrometry, we found 22 cations and 30 anions that accumulated significantly as the estimated glomerular filtration rate (eGFR) decreased. These compounds included 9 cations and 27 anions that were newly identified in this study. In contrast, we also found 7 cations (2 new) and 5 anions (all new) that decrease significantly as eGFR declines. We evaluated each substance for its suitability to detect early CKD stage. Compounds that are highly correlated with eGFR and whose plasma concentration changed in a manner approximated by the first-degree equation are excellent candidates for detecting CKD and identifying uremic toxins that might aggravate kidney function in the early stage of CKD. These results identify a number of uremic compounds, many of which are novel and which predict worsening renal function. These compounds provide diagnostic information and may be targets for therapies designed to treat the complications of CKD patients. Keywords: biomarker; CE-MS; CKD; uremic toxin INTRODUCTION Chronic kidney disease (CKD) is an important public health problem and determination of the glomerular filtration rate (GFR) has been essential for the evaluation of CKD patients. 1-3 Early detection of impairment of renal function allows treatment to prevent further deterioration and complications. With the progression of CKD, various uremic toxins accumulate, subsequently causing renal damage and hypertension. 4,5 Recently, we revealed that many compounds accumulate during renal failure, and that the kidney-specific organic anion transporter SLCO4C1 excretes uremic toxins, resulting in the reduction of blood pressure and renal inflammation. 6 To generalize these results for clinical use, it is necessary to examine the accumulation of uremic solutes precisely. Therefore, the aims of this study were (1) to identify new uremic retention solutes that accumulate in CKD patients comprehensively by capillary electrophoresis with mass spectrometry (CE-MS) and (2) to determine substances that are more sensitive for detecting early renal damage than serum creatinine (Cr) or cystatin C.

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“…The dynamics of renal peptide breakdown and protein synthesis as well as kidneys' capacity for AA interconversions modify the pool of AAs found in renal cells and also influence plasma concentrations (1). In patients with CKD, quantitative and qualitative alterations in the plasma AA profile have been observed (2,3). At an early stage of CKD, plasma concentrations in citrulline, cystine, and taurine have been shown to increase, whereas serine and ornithine were reduced (2).…”

Section: Introductionmentioning

confidence: 99%

“…In patients with CKD, quantitative and qualitative alterations in the plasma AA profile have been observed (2,3). At an early stage of CKD, plasma concentrations in citrulline, cystine, and taurine have been shown to increase, whereas serine and ornithine were reduced (2). At more advanced stages of CKD and after dialysis initiation, alterations in the plasma profile were more pronounced (2,(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…At an early stage of CKD, plasma concentrations in citrulline, cystine, and taurine have been shown to increase, whereas serine and ornithine were reduced (2). At more advanced stages of CKD and after dialysis initiation, alterations in the plasma profile were more pronounced (2,(4)(5)(6). It has been shown that clinical features associated with CKD, such as inflammation or metabolic acidosis, influenced AA and protein metabolism (5,7).…”

Section: Introductionmentioning

confidence: 99%

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

Duranton¹,

Lundin²,

Gayrard³

et al. 2014

Clinical Journal of the American Society of Nephrology

169

124

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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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Early alterations of plasma free amino acids in chronic renal failure

Cited by 99 publications

References 26 publications

GC-MS with ethyl chloroformate derivatization for comprehensive analysis of metabolites in serum and its application to human uremia

GC-MS with ethyl chloroformate derivatization for comprehensive analysis of metabolites in serum and its application to human uremia

Metabolomic profiling of uremic solutes in CKD patients

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

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