Skip to main content Skip to main navigation menu Skip to site footer

A network meta-analysis on comparative efficacy of statins focusing for prevention of contrast-induced acute kidney injury in chronic kidney disease patients undergoing percutaneus coronary intervention


Background: The use of interventional diagnostic and therapeutic procedures required intravascular iodinated contrast are performed in millions of patients worldwide and are steadily increasing the risks of contrast-induced acute kidney injury (CI-AKI). Statins are primarily used in cardiovascular medicine for their lipid-lowering effects but they possess remarkable pleiotropic effects such as improving endothelial function as well as decreasing oxidative stress and inflammation. A network meta-analysis was carried out to evaluate the effect of different statins in prevention of CI-AKI and also to investigate which type and dose of statins maybe the best choice specifically in CKD patients who have higher risk. 

Methods: We performed a pairwise and network meta analysis of 14 randomized studies (9847 patients) comparing a total of 6 different statins: rosuvastatin high dose, atorvastatin high dose, simvastatin high dose, rosuvastatin regular dose, atorvastatin regular dose, pravastatin regular dose versus each other and versus placebo in CKD patients undergoing PCI with iodinated contrast for prevention of CIAKI. Google Scholar, Pubmed, Science Direct databases were searched up to May 2019. The data were pooled using STATA, and R version statistics calculating odds ratios (ORs) with 95% confidence intervals.

Results: Statin loading before contrast administration was associated with a significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization (pooled OR= 0.51; P=0.0001). Regular dose pravastatin comprised the best effect size for a reduction in CIAKI risk (OR = 0.32, 95% CI 0.14-0.72, p=0.006). Regular dose pravastatin and high dose atorvastatin were ranked as the highest probability to be the best treatment (Pbest) with 44% and 31% respectively for effect on CIAKI prevention.

Conclusion: Preloading with statins is associated with significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization. Regular dose pravastatin and high dose atorvastatin have the highest probability to be the most effective prevention strategy.


  1. Abaci O, Harmankaya O, Kocas B, et al. Long-term follow-up of patients at high risk for nephropathy after contrast exposure. Angiology. 2015;66(6):514-8.
  2. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Contrastinduced nephropathy: an “all or none†phenomenon?. Angiology. 2015;66(6):508-13.
  3. Farmer JA.Pleiotropic effects of statins. Current Atherosclerosis Reports. 2000;2(3):208-217.
  4. Shishehbor MH, Aviles RJ, Brennan M. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. The Journal of the American Medical Association. 2003;289(13):1675–1680.
  5. Akyuz S, Yaylak B, Altay S, Kasikcioglu H, Cam N. The role of statins in preventing contrast-induced acute kidney injury: a narrative review. Angiology. 2015;66(8):701-7.
  6. Liu X M, Han Y L, Kui P, Sun L, Pan H, Zhao W, Xu K, LI J. Effect of rosuvastatin on contrast-induced acute kidney injury after percutaneous coronary intervention in elder patients with diabetes associated with mild-moderate renal insufficiency. Med J Chin PLA. 2014;39(4):265-269
  7. Wu H, Han Y L, Wang X, LI Y, Xu K, Li J, Huo Y. Effects of short-term rosuvastatin therapy on heart and kidney function in patients with acute coronary syndrome combining diabetes mellitus and concomitant chronic kidney disease. Med J Chin PLA. 2014;39(1): 546-552
  8. Patti G, Ricottini E, Nusca A, Colonna G, Pasceri V, D’Ambrosio A, et al. Short-term, high-dose atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [atorvastatin for reduction of myocardial damage during angioplasty–contrast-induced nephropathy] trial. Am J Cardiol. 2011;108(1):1–7
  9. Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A, Golia B, et al. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. Circulation. 2012;126(25):3008–16.
  10. Toso A, Maioli M, Leoncini M, Gallopin M, Tedeschi D, Micheletti C, Manzone C, Amato M, Bellandi F. Usefulness of Atorvastatin (80 mg) in Prevention of Contrast-Induced Nephropathy in Patients With Chronic Renal Disease. The American Journal of Cardiology. 20013;105(3):288-292.
  11. Abaci O, Arat Ozkan A, Kocas C, Cetinkal G, Sukru Karaca O, Baydar O, et al. Impact of rosuvastatin on contrast-induced acute kidney injury in patients at high risk for nephropathy undergoing elective angiography. Am J Cardiol. 2015;115(7):867–71.
  12. Leoncini M, Toso A, Maioli M, Tropeano F, Villani S, Bellandi F. Early High-Dose Rosuvastatin for Contrast-Induced Nephropathy Prevention in Acute Coronary Syndrome. Journal of the American College of Cardiology. 2014;63(1):71-79.
  13. Oliveira M, Bomfim Araujo MK, Ribamar CJ, Abizaid A, Stadler J, Alberto Mattos L, et al. Impact on Renal Function of Rosuvastatin Preload Prior to Elective Percutaneous Coronary Intervention in Chronic Statin Users. Revista Brasileira de Cardiologia Invasiva (English Edition). 2012;20(3):303-308.
  14. Jo S, Koo B, Park J, Kang H, Cho Y, et al. Prevention of radiocontrast medium–induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial—a randomized controlled study. American Heart Journal. 2008;155(3):499.e1-499.e8.
  15. Han Y, Zhu G, Xu B, Mehran R, and Huo Y. Short-term statin therapy for prevention of contrast induced-acute kidney injury in patients with diabetes and chronic kidney disease. European Heart Journal. 2013;34(suppl 1):1946-1946.
  16. Yoshida S, Kamihata H, Nakamura S, Senoo T, Manabe K, Motohiro M, Sugiura T, Iwasaka T. Prevention of contrast-induced nephropathy by chronic pravastatin treatment in patients with cardiovascular disease and renal insufficiency. Journal of Cardiology. 2009;54(2):92-198.
  17. Shalaby S, Gamal A, Kandeel O. Efficacy of high-dose atorvastatin in preventing contrast-induced nephropathy in patients undergoing coronary angiography. Menoufia Med J. 2017;31:894-899.
  18. Muñoz M, Maxwell P, Green K, Hughes D, and Talbert R. Pravastatin Versus Simvastatin for Prevention of Contrast-Induced Nephropathy. Journal of Cardiovascular Pharmacology and Therapeutics. 2011;16(4):376-379.
  19. Liu Y, Liu Y, Tan N, Chen J, Zhou Y, Li L, Duan C, Chen P, Luo J, Li H, Wei G. Comparison of the Efficacy of Rosuvastatin versus Atorvastatin in Preventing Contrast Induced Nephropathy in Patient with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention. PLoS ONE. 2014;9(10):e111124.
  20. Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, and Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49(8):1881-1892.
  21. Yada T, Nakata M, Shiraishi T, Kakei M. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+signalling and insulin secretion due to blockade of L-type Ca2+channels in rat islet β-cells. British Journal of Pharmacology. 1999;126(5):1205-1213.
  22. Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T, Nakaya N, Nishimoto S, Muranaka M, Yamamoto A, Mizuno K, Ohashi Y. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. The Lancet. 2006;368(9542):1155-1163.
  23. Lee T, Su S, Tsai C. Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension. Hypertension. 2002;40(1):67-73.
  24. Khanal S, Attallah N, Smithetal DE. Statintherapyreduces contrast-induced nephropathy: an analysis of contemporary percutaneous interventions. American Journal of Medicine. 2005;118(8):843–849.
  25. Aurelio A, Durante A. Contrast-induced nephropathy in percutaneous coronary interventions: pathogenesis, risk factors, outcome, prevention and treatment. Cardiology. 2014;128(1):62-72.
  26. Uzunhasan I, Yildiz A, Arslan S, et al. Contrast-induced acute kidney injury is associated with long-term adverse events in patients with acute coronary syndrome. Angiology. 2017;68(7): 621-6.
  27. Liss P, Nygren A, Olsson U, Ulfendahl HR, Erikson U. Effects of contrast media and mannitol on renal medullary blood flow and red cell aggregation in the rat kidney. Kidney Int.1996;49(5):1268–75.
  28. Liss P. Effects of contrast media on renal microcirculation and oxygen tension. An experimental study in the rat. Acta Radiol Suppl. 1997;409:1–29.
  29. Liss P, Nygren A, Hansell P. Hypoperfusion in the renal outer medulla after injection of contrast media in rats. Acta Radiol. 1999;40(5):521–7.
  30. Sendeski M, Patzak A, Pallone TL, Cao C, Persson AE, Persson PB. Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy. Radiology. 2009;251(3):697–704.
  31. Clark BA, Kim D, Epstein FH. Endothelin and atrial natriuretic peptide levels following radiocontrast exposure in humans. Am J Kidney Dis. 1997;30(1):82–6.
  32. Andreucci M, Lucisano G, Faga T, Bertucci B, Tamburrini O, Pisani A, et al. Differential activation of signaling pathways involved in cell death, survival and inflammation by radiocontrast media in human renal proximal tubular cells. Toxicol Sci. 2011;119(2):408–16.
  33. Caiazza A, Russo L, Sabbatini M, Russo D. Hemodynamic and tubular changes induced by contrast media. Biomed Res Int. 2014;2014:578974.
  34. Heyman SN, Rosen S, Khamaisi M, Ide ´e JM, Rosenberger C. Reactive oxygen species and the pathogenesis of radiocontrastinduced nephropathy. Invest Radiol. 2010;45(4):188–95.
  35. Katholi RE, Woods WT Jr, Taylor GJ, Deitrick CL, Womack KA, Katholi CR, et al. Oxygen free radicals and contrast nephropathy. Am J Kidney Dis. 1998;32(1):64–71.
  36. Walter DH, Dimmeler S, Zeiher AM. Effects of statins on endothelium and endothelial progenitor cell recruitment. Semin Vasc Med. 2004;4(4):385–93.
  37. Ridker PM, Rifai N, Clearï¬eld M, Downs JR, Weis SE, Miles JS, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344(26):1959–65.
  38. Bonnet J, McPherson R, Tedgui A, et al. Comparative effects of 10-mg versus 80-mg Atorvastatin on high-sensitivity C-reactive protein in patients with stable coronary artery disease: results of the CAP (Comparative Atorvastatin Pleiotropic effects) study. Clin Ther. 2008;30(12):2298-313.
  39. Xinwei J, Xianghua F, Jing Z, et al. 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. Am J Cardiol. 2009;104(4):519-24.
  40. Dulak J, Loboda A, Jazwa A, et al. Atorvastatin affects several angiogenic mediators in human endothelial cells. Endothelium. 2005;12(6):233-41.
  41. Abou-Shousha SA, Youssef AI. Interleukin-2 regulatory effect on P-selectin and interleukin-8 production in patients with chronic renal failure. Egypt J Immunol. 2006;13(1):11-8.
  42. Pistolesi V, Regolisti G, Morabito S, et al. Contrast medium induced acute kidney injury: a narrative review. J Nephrol. 2018. doi:10.1007/s40620018-0498-y.
  43. Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond lipid lowering—are they clinically relevant? Eur Heart J. 2003;24(3):225-48.
  44. Mossanen JC, Pracht J, Jansen TU, et al. Elevated soluble urokinase plasminogen activator receptor and proenkephalin serum levels predict the development of acute kidney injury after cardiac surgery. Int J Mol Sci. 2017;18(8):1662-73.
  45. Gianella A, Nobili E, Abbate M, et al. Rosuvastatin treatment prevents progressive kidney inflammation and fibrosis in stroke-prone rats. Am J Pathol. 2007;170(4):1165-1177.
  46. Kiener PA, Davis PM, Murray JL, Youssef S, Rankin BM, Kowala M. Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors. Int Immunopharmacol. 2001;1(1):105-118.
  47. Zhou X, Dai J, Xu X, Wang Z, Xu H, Chen J, Qiu Y, Mao W. Comparative Efficacy of Statins for Prevention of Contrast-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease: A Network Meta-Analysis. Angiology. 2018;70(4):305-316.

How to Cite

Rahman, I. A., Purnamasari, Y., Rewa, V. N., Kasyim, H., Umar, A. R., & Kasim, F. (2019). A network meta-analysis on comparative efficacy of statins focusing for prevention of contrast-induced acute kidney injury in chronic kidney disease patients undergoing percutaneus coronary intervention. Bali Medical Journal, 8(3), 779–787.




Search Panel