Toward proteomics in uroscopy: urinary protein profiles after radiocontrast medium administration.
Previous attempts to use urinary protein profiles for diagnostic purposes have been rather disappointing with respect to their clinical validity, in part because of the insufficient reproducibility, sensitivity, and rapidity of available techniques. Therefore, a newly developed, high-throughput technique, namely surface-enhanced laser desorption/ionization (SELDI) ProteinChip array-time of flight mass spectrometry, was studied, to assess its applicability for protein profiling of urine and to exemplify its use for a group of patients receiving radiocontrast medium. Assessment of the accuracy, sensitivity, and reproducibility of SELDI in test urinary protein profiling was performed. Renal function was studied in 20 male Sprague-Dawley rats before and after intravenous administration of either 1.25 g/kg ioxilan (n = 10) or hypertonic saline solution (n = 10) as a control. Urine samples from 25 patients undergoing cardiac catheterization were obtained before, immediately after, and 6 to 12 h after the procedure. Administration of ioxilan to rats resulted in changes in the abundance of proteins of 9.9, 18.7, 21.0, and 66.3 kD. For patients, even in uncomplicated cases of radiocontrast medium infusion during cardiac catheterization, perturbations in the protein composition occurred but returned to baseline values after 6 to 12 h. Proteins with molecular masses of 9.75, 11.75, 23.5, and 66.4 kD changed in abundance. For patients with impaired renal function, these changes were not reversible within 6 to 12 h. As a proof of principle, one of the peaks, i.e., that at 11.75 kD, was identified as beta(2)-microglobulin. SELDI is a promising tool for the detection, identification, and characterization of trace amounts of proteins in urine. Even for patients without renal complications, proteins with a broad range of molecular masses either appear in or disappear from the urine. Some of these might represent markers of impending nephropathy.
Hampel
Dierk J
DJ
Department of Medicine, Division of Nephrology and Hypertension, State University of New York at Stony Brook, Stony Brook, New York.
Sansome
Christine
C
Department of Medicine, Division of Nephrology and Hypertension, State University of New York at Stony Brook, Stony Brook, New York.
Sha
M A
MA
Ciphergen Biosystems, Inc., Palo Alto, California.
Brodsky
Sergey
S
Department of Medicine, Division of Nephrology and Hypertension, State University of New York at Stony Brook, Stony Brook, New York.
Lawson
William E
WE
Division of Cardiology, State University of New York at Stony Brook, Stony Brook, New York.
Goligorsky
Michael S
MS
Department of Medicine, Division of Nephrology and Hypertension, State University of New York at Stony Brook, Stony Brook, New York.|Department of Physiology, Division of Nephrology and Hypertension, State University of New York at Stony Brook, Stony Brook, New York.
D000818:Animals; D015415:Biomarkers / Q000652:urine; D003287:Contrast Media / Q000008:administration & dosage; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008970:Molecular Weight; D011507:Proteinuria / Q000175:diagnosis / Q000652:urine*; D020543:Proteome; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D003287:Contrast Media; D020543:Proteome