Metabonomics of acute kidney injury in children after cardiac surgery

Division of Systems Toxicology, United States Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Pediatric Nephrology (Impact Factor: 2.86). 04/2008; 23(6):977-84. DOI: 10.1007/s00467-008-0756-7
Source: PubMed


Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.

Download full-text


Available from: Richard D Beger,
  • Source
    • "The emerging field of metabolomics promises immense potential for early diagnosis, therapy monitoring and f pathogenesis of diseases. In the field of nephrology, metabolomics has been efficiently and successfully applied in renal transplantation [14], acute kidney injury (AKI) [15], renal cell carcinoma [16] and diabetic nephropathy (DN) [17]. But few studies have reported the metabolic profile of glomerular diseases including FSGS. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary focal segmental glomerulosclerosis (FSGS) is pathological entity which is characterized by idiopathic steroid-resistant nephrotic syndrome (SRNS) and progression to end-stage renal disease (ESRD) in the majority of affected individuals. Currently, there is no practical noninvasive technique to predict different pathological types of glomerulopathies. In this study, the role of urinary metabolomics in the diagnosis and pathogenesis of FSGS was investigated. NMR-based metabolomics was applied for the urinary metabolic profile in the patients with FSGS (n = 25), membranous nephropathy (MN, n = 24), minimal change disease (MCD, n = 14) and IgA nephropathy (IgAN, n = 26), and healthy controls (CON, n = 35). The acquired data were analyzed using principal component analysis (PCA) followed by orthogonal projections to latent structure discriminant analysis (OPLS-DA). Model validity was verified using permutation tests. FSGS patients were clearly distinguished from healthy controls and other three types of glomerulopathies with good sensitivity and specificity based on their global urinary metabolic profiles. In FSGS patients, urinary levels of glucose, dimethylamine and trimethylamine increased compared with healthy controls, while pyruvate, valine, hippurate, isoleucine, phenylacetylglycine, citrate, tyrosine, 3-methylhistidine and β-hydroxyisovalerate decreased. Additionally, FSGS patients had lower urine N-methylnicotinamide levels compared with other glomerulopathies. NMR-based metabonomic approach is amenable for the noninvasive diagnosis and differential diagnosis of FSGS as well as other glomerulopathies, and it could indicate the possible mechanisms of primary FSGS.
    PLoS ONE 11/2013; 8(11):e78531. DOI:10.1371/journal.pone.0078531 · 3.23 Impact Factor
  • Source
    • "Metabolomic analysis has also proved useful in identifying early urinary biomarkers of acute kidney injury after cardiopulmonary bypass surgery [24]: using ultra-performance liquid chromatography (UPLC)/MS based metabolomic analyses on urine samples collected 4 and again 12 hours after surgery, the authors were able to identify the children that would develop acute kidney injury over the next 3 days. From a clinical standpoint, finding early metabolic biomarkers may improve our understanding of the pathophysiological mechanisms involved in acute kidney injury and enable a timely diagnosis of this disease after pediatric cardiac surgery. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In many fields of medicine there is a growing interest in characterizing diseases at molecular level with a view to developing an individually tailored therapeutic approach. Metabolomics is a novel area that promises to contribute significantly to the characterization of various disease phenotypes and to the identification of personal metabolic features that can predict response to therapies. Based on analytical platforms such as mass spectrometry or NMR-based spectroscopy, the metabolomic approach enables a comprehensive overview of the metabolites, leading to the characterization of the metabolic fingerprint of a given sample. These metabolic fingerprints can then be used to distinguish between different disease phenotypes and to predict a drug's effectiveness and/or toxicity. Several studies published in the last few years applied the metabolomic approach in the field of pediatric medicine. Being a highly informative technique that can be used on samples collected non-invasively (e.g. urine or exhaled breath condensate), metabolomics has appeal for the study of pediatric diseases. Here we present and discuss the pediatric clinical studies that have taken the metabolomic approach.
    Italian Journal of Pediatrics 10/2009; 35(1):30. DOI:10.1186/1824-7288-35-30 · 1.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Concomitant cardiac and renal dysfunction has been termed the cardiorenal syndrome (CRS). This clinical condition usually manifests as heart failure with worsening renal function and occurs frequently in the acute care setting. A consistent definition of CRS has not been universally agreed upon, although a recent classification of CRS describes several subtypes depending on the primary organ injured and the chronicity of the injury. CRS may develop in adults and children and is a strong predictor of morbidity and mortality in hospitalized and ambulatory patients. The underlying physiology of CRS is not well understood, creating a significant challenge for clinicians when treating heart failure patients with renal insufficiency. This review summarizes recent data characterizing the incidence, physiology, and management of children who have heart failure and acute kidney injury.
    Current Heart Failure Reports 09/2009; 6(3):191-198. DOI:10.1007/s11897-009-0027-3
Show more