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      Protective effect of high dose short term statin therapy with normal saline in prevention of contrast-induced nephropathy among iodixanol-receiving patients

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          Abstract

          Contrast media agents are applied for various diagnostic imagines, however, contrast-induced nephropathy (CIN) limits its usage. Statins have been found to prevent CIN via various mechanisms. However, study regarding the beneficial property of simvastatin as a kind of statin is scarce. This study was aimed to evaluate the efficacy of high dose short term statin therapy against nephrotoxicity of iodixanol. 194 patients were divided equally to control and statin-treated groups. Control group (placebo) received normal satin before and after angiography and statin-treated patients received simvastatin (80 mg/day) plus normal saline before and after angiography. Simvastatin and normal saline were started 12 hours before to 12 hours after the procedure, and serum creatinine before and two consecutive days after procedure were assessed. Estimated glomerular filtration rate (eGFR) was calculated using modification of diet in renal disease (MDRD ) method. In the first 24 hours after procedure, there was no difference between two groups, however after 48 hours of treatment, a significant difference for eGFR between two groups with more values in statin treated group was observed (p=0,002). Prophylactic administration of statins along with hydration may be associated with less contrast-induced nephropathy.

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          Contrast-induced Nephropathy

          Contrast-induced nephropathy (CIN) is a serious complication of angiographic procedures resulting from the administration of contrast media (CM). It is the third most common cause of hospital acquired acute renal injury and represents about 12% of the cases. CIN is defined as an elevation of serum creatinine (Scr) of more than 25% or ≥0.5 mg/dl (44 μmol/l) from baseline within 48 h. More sensitive markers of renal injury are desired, therefore, several biomarkers of tubular injury are under evaluation. Multiple risk factors may contribute to the development of CIN; these factors are divided into patient- and procedure-related factors. Treatment of CIN is mainly supportive, consisting mainly of careful fluid and electrolyte management, although dialysis may be required in some cases. The available treatment option makes prevention the corner stone of management. This article will review the recent evidence concerning CIN incidence, diagnosis, and prevention strategies as well as its treatment and prognostic implications.
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            Simvastatin attenuates cisplatin-induced kidney and liver damage in rats.

            Statins have anti-inflammatory effects that are not directly related to their cholesterol-lowering activity. This study aimed to investigate the effect of simvastatin on the extent of tissue damage in cisplatin-induced nephrotoxicity and hepatotoxicity. The rats received a single intravenous injection of 2.5mgkg(-1) cisplatin. Other groups received either simvastatin (1mgkg(-1)) or the vehicle (ethanol:saline) intraperitoneally for 10 days beginning 5 days prior to cisplatin injection. All animals were decapitated 5 days after cisplatin administration. Trunk blood was collected and analyzed for blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), albumin, and total bilirubin levels. The urine samples were used for the calculation of creatinine clearance levels. The kidney and liver samples were stored for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content or were processed for histopathological examinations. Formation of reactive oxygen species in tissue samples was monitored by using chemiluminescence method. Simvastation reduced the extent of both kidney and liver damage and preserved both kidney and liver functions (p<0.01-0.001). Increase in liver MDA level with a concomitant reduction in GSH in the cisplatin group was attenuated by simvastatin treatment (p<0.05-0.01). Increase in tissue collagen content and chemiluminescence levels in the kidney and liver samples of the cisplatin group was also reversed by simvastatin (p<0.001). In conclusion, simvastatin is beneficial in cisplatin-induced kidney and liver dysfunction and organ damage in rats via prevention of lipid peroxidation and tissue fibrosis, preservation of antioxidant glutathione, and suppression of neutrophil infiltration.
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              Comparison of usefulness of simvastatin 20 mg versus 80 mg in preventing contrast-induced nephropathy in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

              Contrast-induced nephropathy limits the outcomes of percutaneous coronary intervention (PCI). The present study compared the protective effects of different statin doses on renal function. A total of 228 patients with acute coronary syndrome undergoing selective PCI were randomly divided into simvastatin 20-mg group (S20, n = 115) and simvastatin 80-mg group (S80, n = 113). Serum creatinine was measured at admission, the day of PCI, and 24 and 48 hours after PCI. The creatinine clearance was calculated using the Cochcroft-Gault formula. High-sensitive C-reactive protein, P-selectin, and intercellular adhesion molecule-1 were also measured before and after the procedure. Contrast-induced nephropathy was defined as a postprocedure increase in serum creatinine of > or =0.5 mg/dl or >25% from baseline. The serum creatinine significantly increased after PCI, with the peak value occurring at 24 hours, and then began to decrease. At 48 hours, the serum creatinine had decreased to the baseline level in the S80 group, but it had failed to do so in the S20 group. At 24 and 48 hours after PCI, the serum creatinine was lower in the S80 group than in the S20 group (p <0.05 and p <0.001, respectively). The creatinine clearance significantly decreased after PCI, with the lowest value occurring at 24 hours, and then it began to increase. In the S80 group, the creatinine clearance recovered to baseline level at 48 hours, but it failed to do so in the S20 group. The creatinine clearance was greater at 24 and 48 hours in the S80 group than that in the S20 group. Although the procedure caused a significant increase in high-sensitive C-reactive protein, P-selectin, and intercellular adhesion molecule-1 levels, the value was lower in the S80 group than in the S20 group (p <0.001). In conclusion, pretreatment with simvastatin 80 mg before PCI could further decrease the occurrence of contrast-induced nephropathy compared with simvastatin 20 mg. This benefit was associated with the lowering of high-sensitive C-reactive protein, P-selectin, and intercellular adhesion molecule-1 levels.
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                Author and article information

                Journal
                J Renal Inj Prev
                J Renal Inj Prev
                J Renal Inj Prev
                JRIP
                Journal of Renal Injury Prevention
                Nickan Research Institute
                2345-2781
                2012
                01 January 2012
                : 1
                : 1
                : 43-45
                Affiliations
                1Department of Internal Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
                2Faculty of Health, Zahedan University of Medical Sciences, Zahedan, Iran
                Author notes
                [* ] Corresponding author: Siavosh Abdani, Department of Internal Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. siavoshabdani@ 123456yahoo.com
                Article
                10.12861/jrip.2012.15
                4205974
                25340104
                7318d132-8d2b-44f7-be22-efbe86fe9329
                Copyright © 2012 The Author(s); Published by Nickan Research Institute

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 September 2011
                : 04 December 2011
                Page count
                Tables: 1, References: 6, Pages: 3
                Categories
                Short Communication

                statin,contrast-induced nephropathy,renal failure
                statin, contrast-induced nephropathy, renal failure

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