Monitoring kidney-transplant patients using metabolomics and dynamic modeling

Stenlund, Hans; Madsen, Rasmus Bødker; Vivi, Antonio; Calderisi, Marco; Lundstedt, Torbjörn; Tassini, Maria; Carmellini, Mario; Trygg, Johan

doi:10.1016/j.chemolab.2009.04.013

Cited by 26 publications

(16 citation statements)

References 16 publications

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“…Consequently, there is increasing interest in applying metabolomics during=after clinical organ transplantation for monitoring kidney, heart, and liver (Sarwal, 2009;Wishart, 2005). Examples include a successful attempt to detect acute cardiac rejection by analyzing plasma by proton nuclear magnetic resonance (NMR) spectroscopy (Eugene et al, 1991;Mouly-Bandini et al, 2000); profiling acute renal rejection by gas-chromatography mass spectrometry (Mao et al, 2008); and monitoring kidney transplant patients' immune responses and drug effects in early recovery using urine samples analyzed by NMR (Stenlund et al, 2009). In liver transplantation, NMR-based metabolomics studies have showed that individual metabolites may act as indicators of liver function: for example, primary graft dysfunction may be characterized by constant levels of glycerophosphocholine (in the liver tissue) throughout OLT (Duarte et al, 2005), by increased glutamine levels (serum and urine), and by decreased urea levels (urine) following OLT (Singh et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Application of Metabolomics to Investigate the Process of Human Orthotopic Liver Transplantation: A Proof-of-Principle Study

Hrydziuszko

Silva

Perera

et al. 2010

OMICS: A Journal of Integrative Biology

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To improve the outcome of orthotopic liver transplantation (OLT), knowledge of early molecular events occurring upon ischemia/reperfusion is essential. Powerful approaches for profiling metabolic changes in tissues and biofluids are now available. Our objective was to investigate the applicability of two technologies to a small but well-defined cohort of patients undergoing OLT: consecutive liver biopsies by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and microdialysates of extracellular fluid by coulometric electrochemical array detection (CEAD). FT-ICR MS detected reproducibly more than 4,000 peaks, revealing hundreds of significant metabolic differences between pre- and postreperfusion grafts. These included increased urea production, bile acid synthesis and clearance of preservation solution upon reperfusion, indicating a rapid resumption of biochemical function within the graft. FT-ICR MS also identified successfully the only graft obtained by donation-after-cardiac-death as a "metabolic outlier." CEAD time-profile analysis showed that there was considerable change in redox-active metabolites (up to 18 h postreperfusion), followed by their stabilization. Collectively these results verify the applicability of FT-ICR MS and CEAD for characterizing multiple metabolic pathways during OLT. The success of this proof-of-principle application of these technologies to a clinical setting, considering the potential metabolic heterogeneity across only eight donor livers, is encouraging.

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Section: Introductionmentioning

confidence: 99%

Application of Metabolomics to Investigate the Process of Human Orthotopic Liver Transplantation: A Proof-of-Principle Study

Hrydziuszko

Silva

Perera

et al. 2010

OMICS: A Journal of Integrative Biology

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“…Dynamic modelling , Stenlund et al, 2009) is a methodology that makes it possible to evaluate and handle different types of variations such as individual differences in metabolic kinetics, circadian rhythm, fast and slow responders and is also capable of handling sparse and unevenly sampled time series.…”

Section: Orthogonal Projections To Latent Structures Discriminant Anamentioning

confidence: 99%

“…We therefore used PCA to map the metabolic trajectory for each individual rat in accordance with the dynamic modeling approach , Stenlund et al, 2009). This means that each rat is used as its own reference, allowing subtle changes, specific to each individual rat over time to be examined.…”

Section: Comparison Of Serum Profiles Using Pca and Dynamic Modelingmentioning

confidence: 99%

“…In order to test the hypothesis that metabolic changes in serum predict diabetes we followed with repeat serum metabolomics analyses by LC/MS (Bruce et al, 2008) and GC/MS (A et al, 2005) combined with statistical dynamic modeling , Stenlund et al, 2009, congenic DP BB rats along with their DR1 and DR2 littermates from 40 days of age until the rapid onset of diabetes. In contrast to Oresic et al (2008), our study is specifically addressing to what extent the acute onset of diabetes in the BB rat is preceded by changes in the serum metabolite profile that would distinguish the pre-diabetic DP from the DR BB rats.…”

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Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

et al. 2011

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“…9,10 Metabonomics is also considered as a useful tool for surgeons 11 and monitoring renal transplants early and sensitively. [12][13][14][15][16][17][18] Serkova et al found that allantoin and trimethylamine-N-oxide could be used to quantify the severity of ischemia/reperfusion injury in a rat kidney transplant model based on NMR metabolic signatures. 12 By using a matrix assisted laser desorption-ionization Fourier transform mass spectrometer (MALDI-FTMS) Wang et al found that urinary small molecules were associated with acute renal allograft rejection.…”

Section: Introductionmentioning

confidence: 99%

Metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry

et al. 2012

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Acute graft rejection is one of the most common and serious post complications in renal transplantation, noninvasive diagnosis of acute graft rejection is essential for reducing risk of surgery and timely treatment. In this study, a non-targeted metabonomics approach based on ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (MS) is used to investigate the effect of acute graft rejection in rat renal transplantation on metabolism. To collect more metabolite information both hydrophilic interaction chromatography and reversed-phase liquid chromatography were used. Using the partial least squares-discriminant analysis, we found that the change of metabonome in a shamoperated group and a non-graft rejection group had a similar trend, while that of the acute graft rejection group was clearly different. Several discriminating metabolites of the acute graft rejection were identified, including creatinine, phosphatidyl-cholines, lyso-phosphatidylcholines, carnitine C16:0, free fatty acids and indoxyl sulfate etc. These discriminating metabolites suggested that acute graft rejection in renal transplantation can lead to the accumulation of creatinine in the body, and also the abnormal metabolism of phospholipids. These findings are useful to understand the mechanisms of the rejection, it also means that a UPLC-MS metabonomic approach is a suitable tool to investigate the metabolic abnormality in the acute graft rejection in renal transplantation.

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Monitoring kidney-transplant patients using metabolomics and dynamic modeling

Cited by 26 publications

References 16 publications

Application of Metabolomics to Investigate the Process of Human Orthotopic Liver Transplantation: A Proof-of-Principle Study

Application of Metabolomics to Investigate the Process of Human Orthotopic Liver Transplantation: A Proof-of-Principle Study

Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

Metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry

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