Abstract
BackgroundAcute renal allograft rejection is a common complication after renal transplantation that often leads to chronic rejection and ultimate graft loss. While renal allograft biopsy remains the gold standard for diagnosis of acute rejection, the possibility of biopsy-associated complications cannot be overlooked. The development of noninvasive methods for accurate detection of acute renal allograft rejection is thus of significant clinical importance.MethodsGas chromatography–mass spectrometry (GC/MS) was employed for analysis of urine metabolites in 15 renal allograft recipients with acute rejection and 15 stable renal transplant recipients. Partial least squares (PLS) regression and leave-one-out analyses were performed to ascertain whether the metabolites identified could be exploited to distinguish acute rejection from stable groups as well as their sensitivity and specificity.ResultsOverall, 14 metabolites were significantly altered in the acute rejection group (11 and 3 metabolites displayed higher and lower levels, respectively) relative to the stable transplant group. Data from PLS and leave-one-out analyses revealed that the differential metabolites identified not only distinguished acute rejection from stable transplant recipients but also showed high sensitivity and specificity for diagnosis of renal allograft recipients with acute rejection.ConclusionUrine metabolites identified with GC/MS can effectively distinguish acute rejection from stable transplant recipients, supporting the potential utility of metabolome analysis in non-invasive diagnosis of acute rejection.
Highlights
Acute renal allograft rejection is a common complication after renal transplantation that often leads to chronic rejection and ultimate graft loss
Multiple analytical approaches have been applied for metabolomic analyses, including gas chromatography–mass spectrometry (GC/MS), liquid chromatography–mass spectrometry (LC–MS) and proton nuclear magnetic resonance (NMR) [8,9,10]
After silylation for 30 min, 40 μl heptane was added, the mixture centrifuged at 10,000 rpm for 5 min, and 80 μl supernatant transferred for GC/MS analysis
Summary
Acute renal allograft rejection is a common complication after renal transplantation that often leads to chronic rejection and ultimate graft loss. The development of noninvasive methods for accurate detection of acute renal allograft rejection is of significant clinical importance. Noninvasive methods to accurately detect acute renal allograft rejection are an urgent clinical requirement. Metabolomics, characterized by high-throughput and quantitative measurement of all small-molecule metabolites in the metabolome, targets the similarities and differences between biological samples [6]. This technique has been used in a number of areas, including identification of potential biomarkers of disease, pharmaceutical research, nutrition and botanical science [7]. In combination with bioinformatic and biostatistical analyses, this technology may contribute to the identification and quantification of small-molecule metabolites to characterize whole-organism response to a given disease
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