Metabolomics as an extension of proteomic analysis: study of acute kidney injury.
Although proteomics studies the global expression of proteins, metabolomics characterizes and quantifies their end products: the metabolites, produced by an organism under a certain set of conditions. From this perspective it is apparent that proteomics and metabolomics are complementary and when joined allow a fuller appreciation of an organism's phenotype. Our studies using (1)H-nuclear magnetic resonance spectroscopic analysis showed the presence of glucose, amino acids, and trichloroacetic acid cycle metabolites in the urine after 48 hours of cisplatin administration. These metabolic alterations precede changes in serum creatinine. Biochemical studies confirmed the presence of glucosuria, but also showed the accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and kidney tissue, despite increased levels of plasma insulin. These metabolic alterations were ameliorated by the use of fibrates. We propose that the injury-induced metabolic profile may be used as a biomarker of cisplatin-induced nephrotoxicity. These studies serve to illustrate that metabolomic studies add insight into pathophysiology not provided by proteomic analysis alone.
Portilla
Didier
D
Department of Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. dportilla1@uams.edu
Schnackenberg
Laura
L
Beger
Richard D
RD
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D002945:Cisplatin / Q000633:toxicity; D005227:Fatty Acids / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D047493:PPAR alpha / Q000502:physiology; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D007328:Insulin; D047493:PPAR alpha; D011506:Proteins; D014280:Triglycerides; D005947:Glucose; D002945:Cisplatin