Abstract
Contrast induced nephropathy (CIN) that develops as a result of using contrast after coronary angiography or other diagnostic procedures, has been reported to be the third leading cause of acute renal failure in hospitalized patients but there are limited prognostic and early diagnostic tools .Therefore, a tool that pre-procedural could predict CIN and then early detect the patients already developed CIN would be valuable for patient care. It is been hypothesized that urine metabolomics profile will differ between those patients who will develop CIN after angiography and those who do not after contrast administration. It is believed that urine metabolomics profiles prior to coronary angiography may identify subjects who will go on to develop CIN and are therefore at higher risk. It is also been proposed that urine metabolomics analysis differ in patients who develop CIN post coronary angiography even as early as 6 hours after contrast administration. 100 patients were enrolled in this pilot study. To be eligible patients had to be >18 years old, undergoing elective coronary angiography with glomerular filtration rate > 60 mL/min/1.73 m2. Patients were excluded from the study if they had an estimated glomerular filtration rate <15 mL/min/1.73 m2, a history of organ transplantation, decompensated heart failure, were currently on immunosuppressive medications, were septic or on antibiotic therapy, had a history of or were currently receiving dialysis of any type and had an exposure to iodinated contrast within 3 days prior to the study. All patients received approximately 100 mL of intra-arterial iodinated contrast material that was administered via computer-controlled automated power injector at 4 mL per second. Baseline serum creatinine and urine samples and serum creatinine and urine samples 6, 12, and 72 hours after coronary angiography were collected. Urine metabolomics was done with nuclear magnetic resonance spectroscopy. Spectra were acquired with 154 scans. Predictive biomarker candidates (p-value < 0.05 in U test) with fold change > 1.2 which had been changed or differed in the urine metabolomics analysis before angiography in whom developed CIN later, were included :3-methylhistidine and 11-alpha hydroxyprogestrone (up-regulated) and Taurodeoxycholic acid, 3-methyl-2-oxovaleric acid, D-Glutamine, Epi coprostanol, Phenylalanine, Argininosucssinic acid and Tyrosine (down regulated).Early detection biomarkers with VIP > 1 in multivariate model and fold change > 1.2: Epi-coprostanol (down regulated), Urocanic acid, tyrosine and 11-alphahydroxyprogestrone (up-regulated) These biomarkers were checked against significant variables obtained from OPLS-DA model of non-CIN population before and after angiography, to be sure that their changes are not caused by contrast agent. Differences in urine metabolomics patterns pre coronary angiography in patients, who will and will not develop CIN later, exist. Urine Metabolites may be potential early predictors of CIN . Differences in urine metabolomics patterns also exist in early post coronary angiography frame and can be used as new markers for early detection of post coronary angiography induced CIN even as early as 6 hours after contrast administration.
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