Metabolomic analysis of human plasma from haemodialysis patients
Eur J Clin Invest 2011; 41 (3): 241–255 Background Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we conducted this study to identify novel biomarkers that can be used as alternatives to urea and cr...
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| Published in | European journal of clinical investigation Vol. 41; no. 3; pp. 241 - 255 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.03.2011
Wiley-Blackwell |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0014-2972 1365-2362 1365-2362 |
| DOI | 10.1111/j.1365-2362.2010.02398.x |
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| Abstract | Eur J Clin Invest 2011; 41 (3): 241–255
Background Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we conducted this study to identify novel biomarkers that can be used as alternatives to urea and creatinine to estimate the adequate dialysis dose by metabolomic analyses of plasma samples from patients undergoing haemodialysis.
Material and methods Liquid chromatography–electrospray ionization (ESI)–time‐of‐flight mass spectrometry (MS) was used to analyse low molecular weight molecules present in the plasma samples of 10 patients with end‐stage renal disease (ESRD) who were being treated with haemodialysis, and in 16 healthy subjects.
Results In plasma samples obtained after haemodialysis, the relative quantities of 54 peaks were significantly (P < 0·05) decreased when compared with those in the plasma before haemodialysis. The candidate biomarkers were allocated to three groups. Molecules in Group A improved completely with a large variance, molecules in Group B improved partially but with a large variance, and molecules in Group C improved partially with low variance after haemodialysis. Small cohort validation study consisting of the patients with ESRD undergoing haemodialysis indicates that three candidate biomarkers in Group C would be a very useful marker to estimate adequate haemodialysis dose.
Conclusions 1‐Methylinosine and two unknown molecules whose m/z at ESI‐positive mode are 257·1033 and 413·1359 were found as effective candidate biomarkers to estimate adequate haemodialysis dose, which has to be confirmed in prospective studies. |
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| AbstractList | Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we conducted this study to identify novel biomarkers that can be used as alternatives to urea and creatinine to estimate the adequate dialysis dose by metabolomic analyses of plasma samples from patients undergoing haemodialysis.BACKGROUNDUrea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we conducted this study to identify novel biomarkers that can be used as alternatives to urea and creatinine to estimate the adequate dialysis dose by metabolomic analyses of plasma samples from patients undergoing haemodialysis.Liquid chromatography-electrospray ionization (ESI)-time-of-flight mass spectrometry (MS) was used to analyse low molecular weight molecules present in the plasma samples of 10 patients with end-stage renal disease (ESRD) who were being treated with haemodialysis, and in 16 healthy subjects.MATERIAL AND METHODSLiquid chromatography-electrospray ionization (ESI)-time-of-flight mass spectrometry (MS) was used to analyse low molecular weight molecules present in the plasma samples of 10 patients with end-stage renal disease (ESRD) who were being treated with haemodialysis, and in 16 healthy subjects.In plasma samples obtained after haemodialysis, the relative quantities of 54 peaks were significantly (P < 0·05) decreased when compared with those in the plasma before haemodialysis. The candidate biomarkers were allocated to three groups. Molecules in Group A improved completely with a large variance, molecules in Group B improved partially but with a large variance, and molecules in Group C improved partially with low variance after haemodialysis. Small cohort validation study consisting of the patients with ESRD undergoing haemodialysis indicates that three candidate biomarkers in Group C would be a very useful marker to estimate adequate haemodialysis dose.RESULTSIn plasma samples obtained after haemodialysis, the relative quantities of 54 peaks were significantly (P < 0·05) decreased when compared with those in the plasma before haemodialysis. The candidate biomarkers were allocated to three groups. Molecules in Group A improved completely with a large variance, molecules in Group B improved partially but with a large variance, and molecules in Group C improved partially with low variance after haemodialysis. Small cohort validation study consisting of the patients with ESRD undergoing haemodialysis indicates that three candidate biomarkers in Group C would be a very useful marker to estimate adequate haemodialysis dose.1-Methylinosine and two unknown molecules whose m/z at ESI-positive mode are 257·1033 and 413·1359 were found as effective candidate biomarkers to estimate adequate haemodialysis dose, which has to be confirmed in prospective studies.CONCLUSIONS1-Methylinosine and two unknown molecules whose m/z at ESI-positive mode are 257·1033 and 413·1359 were found as effective candidate biomarkers to estimate adequate haemodialysis dose, which has to be confirmed in prospective studies. Eur J Clin Invest 2011; 41 (3): 241–255 Background Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we conducted this study to identify novel biomarkers that can be used as alternatives to urea and creatinine to estimate the adequate dialysis dose by metabolomic analyses of plasma samples from patients undergoing haemodialysis. Material and methods Liquid chromatography–electrospray ionization (ESI)–time‐of‐flight mass spectrometry (MS) was used to analyse low molecular weight molecules present in the plasma samples of 10 patients with end‐stage renal disease (ESRD) who were being treated with haemodialysis, and in 16 healthy subjects. Results In plasma samples obtained after haemodialysis, the relative quantities of 54 peaks were significantly (P < 0·05) decreased when compared with those in the plasma before haemodialysis. The candidate biomarkers were allocated to three groups. Molecules in Group A improved completely with a large variance, molecules in Group B improved partially but with a large variance, and molecules in Group C improved partially with low variance after haemodialysis. Small cohort validation study consisting of the patients with ESRD undergoing haemodialysis indicates that three candidate biomarkers in Group C would be a very useful marker to estimate adequate haemodialysis dose. Conclusions 1‐Methylinosine and two unknown molecules whose m/z at ESI‐positive mode are 257·1033 and 413·1359 were found as effective candidate biomarkers to estimate adequate haemodialysis dose, which has to be confirmed in prospective studies. Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we conducted this study to identify novel biomarkers that can be used as alternatives to urea and creatinine to estimate the adequate dialysis dose by metabolomic analyses of plasma samples from patients undergoing haemodialysis. Liquid chromatography-electrospray ionization (ESI)-time-of-flight mass spectrometry (MS) was used to analyse low molecular weight molecules present in the plasma samples of 10 patients with end-stage renal disease (ESRD) who were being treated with haemodialysis, and in 16 healthy subjects. In plasma samples obtained after haemodialysis, the relative quantities of 54 peaks were significantly (P < 0·05) decreased when compared with those in the plasma before haemodialysis. The candidate biomarkers were allocated to three groups. Molecules in Group A improved completely with a large variance, molecules in Group B improved partially but with a large variance, and molecules in Group C improved partially with low variance after haemodialysis. Small cohort validation study consisting of the patients with ESRD undergoing haemodialysis indicates that three candidate biomarkers in Group C would be a very useful marker to estimate adequate haemodialysis dose. 1-Methylinosine and two unknown molecules whose m/z at ESI-positive mode are 257·1033 and 413·1359 were found as effective candidate biomarkers to estimate adequate haemodialysis dose, which has to be confirmed in prospective studies. |
| Author | Fujiwara, Kouichi Yamamoto, Masanori Tanaka, Noriaki Sato, Emiko Kohno, Masahiro Fujisawa, Tatsuya |
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| Keywords | Kidney disease Human Urinary system disease Hemodialysis Biological marker haemodialysis Biological indicator Patient Liquid chromatography Blood plasma Medicine uraemic toxin Extrarenal dialysis Toxin LC-MS/MS Mass spectrometry MS/MS Renal failure Biomarkers |
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| References | Lindon JC, Holmes E, Nicholson JK. Metabonomics techniques and applications to pharmaceutical research & development. Pharm Res 2006;23:1075-88. Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 2003;63:1934-43. Lesaffer G, De Smet R, Lameire N, Dhondt A, Duym P, Vanholder R. Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane. Nephrol Dial Transplant 2000;15:50-7. Lysaght MJ. Maintenance dialysis population dynamics: current trends and long-term implications. J Am Soc Nephrol 2002;13(Suppl. 1):S37-40. Chan W, Cai Z. Aristolochic acid induced changes in the metabolic profile of rat urine. J Pharm Biomed Anal 2008;46:757-62. Morton AR, Singer MA. The problem with Kt/V: dialysis dose should be normalized to metabolic rate not volume. Semin Dial 2007;20:12-5. Fenn JB. Electrospray wings for molecular elephants (Nobel Lecture). Angew Chem Int Ed 2003;42:3871. Li HY, Wang SM, Liu HM, Bu SS, Li J, Han D et al. Separation and identification of purine nucleosides in the urine of patients with malignant cancer by reverse phase liquid chromatography/electrospray tandem mass spectrometry. J Mass Spectrom 2009;44:641-51. Bond A, Dudley E, Lemiere F, Tuytten R, El-Sharkawi S, Brenton AG et al. Analysis of urinary nucleosides. V. Identification of urinary pyrimidine nucleosides by liquid chromatography/electrospray mass spectrometry. Rapid Commun Mass Spectrom 2006;20:137-50. Vanholder R, DeSmet R, Lesaffer G. Dissociation between dialysis adequacy and Kt/V. Semin Dial 2002;15:3-7. Wang X, Lv H, Zhang G, Sun W, Zhou D, Jiao G et al. Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples. J Sep Sci 2008;31:2994-3001. Dudley E, Lemiere F, Van Dongen W, Tuytten R, El-Sharkawi S, Brenton AG et al. Analysis of urinary nucleosides. IV. Identification of urinary purine nucleosides by liquid chromatography/electrospray mass spectrometry. Rapid Commun Mass Spectrom 2004;18:2730-8. Vanholder R, De Smet R. Pathophysiologic effects of uremic retention solutes. J Am Soc Nephrol 1999;10:1815-23. Kim K, Aronov P, Zakharkin SO, Anderson D, Perroud B, Thompson IM et al. Urine metabolomics analysis for kidney cancer detection and biomarker discovery. Mol Cell Proteomics 2009;8:558-70. Lemmel C, Stevanovic S. The use of HPLC-MS in T-cell epitope identification. Methods 2003;29:248-59. Iseki K. Chronic kidney disease in Japan. Intern Med 2008;47:681-9. 2009; 44 2002; 15 2006; 20 2006; 23 2004; 18 2000; 15 2002; 13 2008; 47 1999; 10 2008; 46 2009; 8 2003; 29 2008; 31 2007; 20 2003; 63 2003; 42 |
| References_xml | – reference: Dudley E, Lemiere F, Van Dongen W, Tuytten R, El-Sharkawi S, Brenton AG et al. Analysis of urinary nucleosides. IV. Identification of urinary purine nucleosides by liquid chromatography/electrospray mass spectrometry. Rapid Commun Mass Spectrom 2004;18:2730-8. – reference: Chan W, Cai Z. Aristolochic acid induced changes in the metabolic profile of rat urine. J Pharm Biomed Anal 2008;46:757-62. – reference: Vanholder R, DeSmet R, Lesaffer G. Dissociation between dialysis adequacy and Kt/V. Semin Dial 2002;15:3-7. – reference: Lesaffer G, De Smet R, Lameire N, Dhondt A, Duym P, Vanholder R. Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane. Nephrol Dial Transplant 2000;15:50-7. – reference: Wang X, Lv H, Zhang G, Sun W, Zhou D, Jiao G et al. Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples. J Sep Sci 2008;31:2994-3001. – reference: Fenn JB. Electrospray wings for molecular elephants (Nobel Lecture). Angew Chem Int Ed 2003;42:3871. – reference: Iseki K. Chronic kidney disease in Japan. Intern Med 2008;47:681-9. – reference: Vanholder R, De Smet R. Pathophysiologic effects of uremic retention solutes. J Am Soc Nephrol 1999;10:1815-23. – reference: Kim K, Aronov P, Zakharkin SO, Anderson D, Perroud B, Thompson IM et al. Urine metabolomics analysis for kidney cancer detection and biomarker discovery. Mol Cell Proteomics 2009;8:558-70. – reference: Li HY, Wang SM, Liu HM, Bu SS, Li J, Han D et al. Separation and identification of purine nucleosides in the urine of patients with malignant cancer by reverse phase liquid chromatography/electrospray tandem mass spectrometry. J Mass Spectrom 2009;44:641-51. – reference: Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P et al. 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Identification of urinary purine nucleosides by liquid chromatography/electrospray mass spectrometry publication-title: Rapid Commun Mass Spectrom – volume: 8 start-page: 558 year: 2009 end-page: 70 article-title: Urine metabolomics analysis for kidney cancer detection and biomarker discovery publication-title: Mol Cell Proteomics – volume: 23 start-page: 1075 year: 2006 end-page: 88 article-title: Metabonomics techniques and applications to pharmaceutical research & development publication-title: Pharm Res – volume: 20 start-page: 12 year: 2007 end-page: 5 article-title: The problem with Kt/V: dialysis dose should be normalized to metabolic rate not volume publication-title: Semin Dial – volume: 47 start-page: 681 year: 2008 end-page: 9 article-title: Chronic kidney disease in Japan publication-title: Intern Med – volume: 10 start-page: 1815 year: 1999 end-page: 23 article-title: Pathophysiologic effects of uremic retention solutes publication-title: J Am Soc Nephrol – volume: 29 start-page: 248 year: 2003 end-page: 59 article-title: The use of HPLC–MS in T‐cell epitope identification publication-title: Methods – volume: 63 start-page: 1934 year: 2003 end-page: 43 article-title: Review on uremic toxins: classification, concentration, and interindividual variability publication-title: Kidney Int – volume: 20 start-page: 137 year: 2006 end-page: 50 article-title: Analysis of urinary nucleosides. V. Identification of urinary pyrimidine nucleosides by liquid chromatography/electrospray mass spectrometry publication-title: Rapid Commun Mass Spectrom – volume: 46 start-page: 757 year: 2008 end-page: 62 article-title: Aristolochic acid induced changes in the metabolic profile of rat urine publication-title: J Pharm Biomed Anal – volume: 42 start-page: 3871 year: 2003 article-title: Electrospray wings for molecular elephants (Nobel Lecture) publication-title: Angew Chem Int Ed – volume: 13 start-page: S37 issue: Suppl. 1 year: 2002 end-page: 40 article-title: Maintenance dialysis population dynamics: current trends and long‐term implications publication-title: J Am Soc Nephrol – volume: 15 start-page: 50 year: 2000 end-page: 7 article-title: Intradialytic removal of protein‐bound uraemic toxins: role of solute characteristics and of dialyser membrane publication-title: Nephrol Dial Transplant – volume: 44 start-page: 641 year: 2009 end-page: 51 article-title: Separation and identification of purine nucleosides in the urine of patients with malignant cancer by reverse phase liquid chromatography/electrospray tandem mass spectrometry publication-title: J Mass Spectrom – volume: 15 start-page: 3 year: 2002 end-page: 7 article-title: Dissociation between dialysis adequacy and Kt/V publication-title: Semin Dial |
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Background Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been... Urea and creatinine are widely used as biomarkers for disease. However, these parameters have been criticized as markers for several reasons. Thus, we... |
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| SubjectTerms | Adult Aged Aged, 80 and over Analysis of Variance Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Biomarkers Biomarkers - analysis Biomarkers - blood Case-Control Studies Cohort Studies Creatinine - analysis Creatinine - blood Emergency and intensive care: renal failure. Dialysis management Female General aspects haemodialysis Humans Intensive care medicine Kidney Failure, Chronic - blood Kidney Failure, Chronic - therapy Kidney Function Tests LC-MS/MS Male Medical sciences Metabolomics - methods Middle Aged Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Renal Dialysis - methods Renal failure uraemic toxin Urea - analysis Urea - blood |
| Title | Metabolomic analysis of human plasma from haemodialysis patients |
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