Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury.
Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates.
Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3μg/mmol versus 533.6μg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups.
Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.
O’Sullivan S, Healy DA, Moloney MC, Grace PA, Walsh SR. The role of N-acetylcysteine in the prevention of contrast-induced nephropathy in patients undergoing peripheral angiography: A structured review and meta-analysis. Angiology. 2013;64(8):576–82. doi: 10.1177/0003319712467223. Review. PMID:23188834.
Spargias K, Alexopoulos A, Kyrzopoulos S, Iacovis P, Greenwood D, Manginas A, Voudris V, Pavlides G, Buller C, Kremastinos D, Cokkinos D. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation. 2004;110:2837–42. CrossRefPubMed
Zhou L, Chen H. Prevention of contrast-induced nephropathy with ascorbic acid. Int Med. 2012;51(6):531–5. CrossRef
Tee H, Jan M, Bae S. A1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo. Am J Physiol Renal. 2006;290(6):1367–75. CrossRef
Weisbord SD, Kip KE, Saul MI, Palevsky PM. Defining clinically significant radiocontrast nephropathy. J Am Soc Nephrol. 2003;14:280A–1A.
Noorani A, Sadat U, Chowdhury MM, Rollins KE, Harrison SC, Usman A, Burling K, Nordon AG, Boyle JR. Use of urinary biomarkers for assessment of renal injury in patients undergoing EVAR. Angiology. 2016. [Epub ahead of print].
Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N, McCullough PA. CIN Consensus Working Panel. Pathophysiology of contrast-induced nephropathy. Am J Cardiol. 2006;98(6):14–20. CrossRef
- Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy
M. P. Baker
J. R. Boyle
- BioMed Central
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