Metabolomics as an Extension of Proteomic Analysis: Study of Acute Kidney Injury

Portilla, Didier; Schnackenberg, Laura K.; Beger, Richard D.

doi:10.1016/j.semnephrol.2007.09.006

Cited by 46 publications

(40 citation statements)

References 42 publications

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“…Overlap of the signals and volume calculation under signals (the concentration of compounds) were made automatically by the author's program. Our study showed high level of glucose, similar to mouse investigation [14,16]. Also, increased concentrations of alanine, valine, isoleucine and leucine in the urine after the cisplatin infusion were found.…”

Section: Discussionsupporting

confidence: 88%

“…Only Portilla et al [16] used one dimension 1 H NMR spectra. In our own investigation two-dimensional JRES spectra were obtained, which eliminate the overlapping of signals in 1 H NMR and the separation of multiplets (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The result of these abnormalities is the increased urinary excretion of AA, which in properly functioning kidneys is minimized [1,16,[20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

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Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment

Doskocz¹,

Marchewka²,

Jeż³

et al. 2015

Adv Clin Exp Med

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Background. Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney. Objectives. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined. Material and Methods. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles. Results. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p ≤ 0.05, p ≤ 0.01). Conclusions. There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program (Adv Clin Exp Med 2015, 24, 4, 629-635).

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment

Doskocz¹,

Marchewka²,

Jeż³

et al. 2015

Adv Clin Exp Med

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“…The last few years has seen a number of studies investigating changes in metabolites accompanying AKI, especially with respect to the use of nephrotoxins such as cisplatin. 175,176 A recent study investigated changes in the metabolic profiles in a mouse model of IRI, in which a period of renal ischemia was followed by 2 hours to 7 days of reperfusion, 177 using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry analysis. There were changes in metabolites related to energy and purine metabolism as well as osmotic regulation and inflammation.…”

Section: Metabolomic Studies To Identify Biomarkersmentioning

confidence: 99%

The potential use of biomarkers in predicting contrast-induced acute kidney injury

Andreucci¹,

Faga²,

Riccio³

et al. 2016

IJNRD

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Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect.

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“…Since the kidney is the major organ for excreting metabolic end products, its injury can cause changes in the renal metabolic profile, and understanding its influence on kidney function will shed light on new potential diagnostic markers and therapeutic targets in AKI (17,21,34,43). Advances in functional genomics and proteomics have fostered progress in our understanding of the pathogenic mechanisms involved and identified some novel protein biomarkers and candidate therapeutic targets in plasma, urine, and tissues which precede changes in commonly used clinical markers of renal dysfunction like plasma creatinine (6,14,18,29,41). Comparatively little, however, is known regarding the role of lipids in pathogenic mechanisms of AKI (1,5,39).…”

mentioning

confidence: 99%

Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

Rao

Walters

Wilson

et al. 2016

American Journal of Physiology-Renal Physiology

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Acute kidney injury (AKI) is one of the leading causes of in-hospital morbidity and mortality, particularly in critically ill patients. Although our understanding of AKI at the molecular level remains limited due to its complex pathophysiology, recent advances in both quantitative and spatial mass spectrometric approaches offer new opportunities to assess the significance of renal metabolomic changes in AKI models. In this study, we evaluated lipid changes in early ischemia-reperfusion (IR)-related AKI in mice by using sequential window acquisition of all theoretical spectra (SWATH)-mass spectrometry (MS) lipidomics. We found a significant increase in two abundant ether-linked phospholipids following IR at 6 h postinjury, a plasmanyl choline, phosphatidylcholine (PC) O-38:1 (O-18:0, 20:1), and a plasmalogen, phosphatidylethanolamine (PE) O-42:3 (O-20:1, 22:2). Both of these lipids correlated with the severity of AKI as measured by plasma creatinine. In addition to many more renal lipid changes associated with more severe AKI, PC O-38:1 elevations were maintained at 24 h post-IR, while renal PE O-42:3 levels decreased, as were all ether PEs detected by SWATH-MS at this later time point. To further assess the significance of this early increase in PC O-38:1, we used matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to determine that it occurred in proximal tubules, a region of the kidney that is most prone to IR injury and also rich in the rate-limiting enzymes involved in ether-linked phospholipid biosynthesis. Use of SWATH-MS lipidomics in conjunction with MALDI-IMS for lipid localization will help in elucidating the role of lipids in the pathobiology of AKI.

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Metabolomics as an Extension of Proteomic Analysis: Study of Acute Kidney Injury

Cited by 46 publications

References 42 publications

Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment

Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment

The potential use of biomarkers in predicting contrast-induced acute kidney injury

Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

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