Pathophysiology of Contrast-Induced Acute Kidney Injury (CIAKI)

Author(s): Georgios Vlachopanos, Dimitrios Schizas, Natasha Hasemaki, Argyrios Georgalis*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 44 , 2019

Become EABM
Become Reviewer

Abstract:

Contrast-induced acute kidney injury (CIAKI) is a severe complication associated with the use of iodinated contrast media (CM); a sudden but potentially reversible fall in glomerular filtration rate (GFR) typically occurring 48-72 hours after CM administration. Principal risk factors related with the presentation of CIAKI are preexisting chronic kidney disease and diabetes mellitus. Studies on CIAKI present considerable complexity because of differences in CM type and dose, controversies in definition and baseline comorbidities. Despite that, it should be noted that CIAKI poses a serious health problem because it is a very common cause of hospitalacquired AKI, linked to increased morbidity and mortality and utilizing growing healthcare resources. The pathogenesis of CIAKI is heterogeneous and, thus, is incompletely understood. Three basic mechanisms appear to simultaneously occur for CIAKI development: Renal vasoconstriction and medullary hypoxia, tubular cell toxicity and reactive oxygen species formation. The relative contribution of each one of these mechanisms is unknown but they ultimately lead to epithelial and endothelial cell apoptosis and GFR reduction. Further research is needed in order to better clarify CIAKI pathophysiology and accordingly introduce effective preventive and therapeutic strategies.

Keywords: Acute kidney injury, AKI, contrast-induced nephropathy, iodinated contrast media, radiocontrast, pathophysiology, pathogenesis, nephrotoxicity.

[1]
Stacul F, van der Molen AJ, Reimer P, et al. Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 2011; 21(12): 2527-41.
[http://dx.doi.org/10.1007/s00330-011-2225-0] [PMID: 21866433]
[2]
Thomsen HS, Morcos SK, Barrett BJ. Contrast-induced nephropathy: the wheel has turned 360 degrees. Acta Radiol 2008; 49(6): 646-57.
[http://dx.doi.org/10.1080/02841850801995413] [PMID: 18568557]
[3]
Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis 2002; 39(5): 930-6.
[http://dx.doi.org/10.1053/ajkd.2002.32766] [PMID: 11979336]
[4]
Tsai TT, Patel UD, Chang TI, et al. Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry. JACC Cardiovasc Interv 2014; 7(1): 1-9.
[http://dx.doi.org/10.1016/j.jcin.2013.06.016] [PMID: 24456715]
[5]
Rao QA, Newhouse JH. Risk of nephropathy after intravenous administration of contrast material: a critical literature analysis. Radiology 2006; 239(2): 392-7.
[http://dx.doi.org/10.1148/radiol.2392050413] [PMID: 16543592]
[6]
Newhouse JH, Kho D, Rao QA, Starren J. Frequency of serum creatinine changes in the absence of iodinated contrast material: implications for studies of contrast nephrotoxicity. AJR Am J Roentgenol 2008; 191(2): 376-82.
[http://dx.doi.org/10.2214/AJR.07.3280] [PMID: 18647905]
[7]
Davenport MS, Khalatbari S, Cohan RH, Dillman JR, Myles JD, Ellis JH. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology 2013; 268(3): 719-28.
[http://dx.doi.org/10.1148/radiol.13122276] [PMID: 23579046]
[8]
Wallingford VH. The development of organic iodine compounds as x-ray contrast media. J Am Pharm Assoc Am Pharm Assoc 1953; 42(12): 721-8.
[http://dx.doi.org/10.1002/jps.3030421206] [PMID: 13108780]
[9]
Buschur M, Aspelin P. Contrast media: history and chemical properties. Interv Cardiol Clin 2014; 3(3): 333-9.
[PMID: 28582217]
[10]
Lautin EM, Freeman NJ, Schoenfeld AH, et al. Radiocontrast-associated renal dysfunction: a comparison of lower-osmolality and conventional high-osmolality contrast media. AJR Am J Roentgenol 1991; 157(1): 59-65.
[http://dx.doi.org/10.2214/ajr.157.1.2048540] [PMID: 2048540]
[11]
Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M. Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology 2005; 235(3): 843-9.
[http://dx.doi.org/10.1148/radiol.2353040726] [PMID: 15845795]
[12]
Eng J, Wilson RF, Subramaniam RM, et al. Comparative effect of contrast media type on the incidence of contrast-induced nephropathy: a systematic review and meta-analysis. Ann Intern Med 2016; 164(6): 417-24.
[http://dx.doi.org/10.7326/M15-1402] [PMID: 26830055]
[13]
Kane GC, Doyle BJ, Lerman A, Barsness GW, Best PJ, Rihal CS. Ultra-low contrast volumes reduce rates of contrast-induced nephropathy in patients with chronic kidney disease undergoing coronary angiography. J Am Coll Cardiol 2008; 51(1): 89-90.
[http://dx.doi.org/10.1016/j.jacc.2007.09.019] [PMID: 18174044]
[14]
McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997; 103(5): 368-75.
[http://dx.doi.org/10.1016/S0002-9343(97)00150-2] [PMID: 9375704]
[15]
Taliercio CP, Vlietstra RE, Fisher LD, Burnett JC. Risks for renal dysfunction with cardiac angiography. Ann Intern Med 1986; 104(4): 501-4.
[http://dx.doi.org/10.7326/0003-4819-104-4-501] [PMID: 3954277]
[16]
Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy. AJR Am J Roentgenol 2004; 183(6): 1673-89.
[http://dx.doi.org/10.2214/ajr.183.6.01831673] [PMID: 15547209]
[17]
Dong M, Jiao Z, Liu T, Guo F, Li G. Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials. J Nephrol 2012; 25(3): 290-301.
[http://dx.doi.org/10.5301/jn.5000067] [PMID: 22252847]
[18]
McDonald JS, McDonald RJ, Comin J, et al. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology 2013; 267(1): 119-28.
[http://dx.doi.org/10.1148/radiol.12121460] [PMID: 23319662]
[19]
Speck U. Contrast media: overview, use and pharmaceutical aspects. 4th ed. Berlin, Heidelberg, New York: Springer 1999; pp. 8-83.
[http://dx.doi.org/10.1007/978-3-642-85995-3_1]
[20]
Geenen RW, Kingma HJ, van der Molen AJ. Contrast-induced nephropathy: pharmacology, pathophysiology and prevention. Insights Imaging 2013; 4(6): 811-20.
[http://dx.doi.org/10.1007/s13244-013-0291-3] [PMID: 24092564]
[21]
Calvin AD, Misra S, Pflueger A. Contrast-induced acute kidney injury and diabetic nephropathy. Nat Rev Nephrol 2010; 6(11): 679-88.
[http://dx.doi.org/10.1038/nrneph.2010.116] [PMID: 20877303]
[22]
Heyman SN, Rosen S, Khamaisi M, Idée JM, Rosenberger C. Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy. Invest Radiol 2010; 45(4): 188-95.
[http://dx.doi.org/10.1097/RLI.0b013e3181d2eed8] [PMID: 20195159]
[23]
Liu ZZ, Viegas VU, Perlewitz A, et al. Iodinated contrast media differentially affect afferent and efferent arteriolar tone and reactivity in mice: a possible explanation for reduced glomerular filtration rate. Radiology 2012; 265(3): 762-71.
[http://dx.doi.org/10.1148/radiol.12120044] [PMID: 23023964]
[24]
Heyman SN, Rosen S, Rosenberger C. Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy. Clin J Am Soc Nephrol 2008; 3(1): 288-96.
[http://dx.doi.org/10.2215/CJN.02600607] [PMID: 18057308]
[25]
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.
[http://dx.doi.org/10.1148/radiol.2513081732] [PMID: 19366904]
[26]
Sendeski MM, Persson AB, Liu ZZ, et al. Iodinated contrast media cause endothelial damage leading to vasoconstriction of human and rat vasa recta. Am J Physiol Renal Physiol 2012; 303(12): F1592-8.
[http://dx.doi.org/10.1152/ajprenal.00471.2012] [PMID: 23077094]
[27]
Heyman SN, Clark BA, Kaiser N, et al. Radiocontrast agents induce endothelin release in vivo and in vitro. J Am Soc Nephrol 1992; 3(1): 58-65.
[PMID: 1391709]
[28]
Ueda J, Nygren A, Hansell P, Ulfendahl HR. Effect of intravenous contrast media on proximal and distal tubular hydrostatic pressure in the rat kidney. Acta Radiol 1993; 34(1): 83-7.
[http://dx.doi.org/10.1177/028418519303400117] [PMID: 8427755]
[29]
Schwab SJ, Hlatky MA, Pieper KS, et al. Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent. N Engl J Med 1989; 320(3): 149-53.
[http://dx.doi.org/10.1056/NEJM198901193200304] [PMID: 2643042]
[30]
Liu ZZ, Schmerbach K, Lu Y, et al. Iodinated contrast media cause direct tubular cell damage, leading to oxidative stress, low nitric oxide, and impairment of tubuloglomerular feedback. Am J Physiol Renal Physiol 2014; 306(8): F864-72.
[http://dx.doi.org/10.1152/ajprenal.00302.2013] [PMID: 24431205]
[31]
Guitterez NV, Diaz A, Timmis GC, et al. Determinants of serum creatinine trajectory in acute contrast nephropathy. J Interv Cardiol 2002; 15(5): 349-54.
[http://dx.doi.org/10.1111/j.1540-8183.2002.tb01067.x] [PMID: 12440177]
[32]
Kennedy-Lydon TM, Crawford C, Wildman SS, Peppiatt-Wildman CM. Renal pericytes: regulators of medullary blood flow. Acta Physiol (Oxf) 2013; 207(2): 212-25.
[http://dx.doi.org/10.1111/apha.12026] [PMID: 23126245]
[33]
Patzak A, Carlström M, Sendeski MM, et al. Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate. Acta Physiol (Oxf) 2015; 213(1): 285-93.
[http://dx.doi.org/10.1111/apha.12425] [PMID: 25394939]
[34]
Rabelink TJ, de Zeeuw D. The glycocalyx--linking albuminuria with renal and cardiovascular disease. Nat Rev Nephrol 2015; 11(11): 667-76.
[http://dx.doi.org/10.1038/nrneph.2015.162] [PMID: 26460356]
[35]
Li LP, Lu J, Franklin T, Zhou Y, Solomon R, Prasad PV. Effect of iodinated contrast medium in diabetic rat kidneys as evaluated by blood-oxygenation-level-dependent magnetic resonance imaging and urinary neutrophil gelatinase-associated lipocalin. Invest Radiol 2015; 50(6): 392-6.
[http://dx.doi.org/10.1097/RLI.0000000000000141] [PMID: 25668748]
[36]
Koneth I, Weishaupt D, Bachli EB. Persistent nephrogram after administration of an isoosmolar contrast medium. Nephrol Dial Transplant 2004; 19(6): 1654-5.
[http://dx.doi.org/10.1093/ndt/gfh157] [PMID: 15150366]
[37]
Akrawinthawong K, Ricci J, Cannon L, et al. Subclinical and clinical contrast-induced acute kidney injury: data from a novel blood marker for determining the risk of developing contrast-induced nephropathy (ENCINO), a prospective study. Ren Fail 2015; 37(2): 187-91.
[http://dx.doi.org/10.3109/0886022X.2014.991994] [PMID: 25519207]
[38]
Tervahartiala P, Kivisaari L, Kivisaari R, Vehmas T, Virtanen I. Structural changes in the enal proximal tubular cells induced by iodinated contrast media. Nephron 1997; 76(1): 96-102.
[39]
Michael A, Faga T, Pisani A, et al. Molecular mechanisms of renal cellular nephrotoxicity due to radiocontrast media. BioMed Res Int 2014; 2014 249810
[http://dx.doi.org/10.1155/2014/249810] [PMID: 24745009]
[40]
Andersen KJ, Christensen EI, Vik H. Effects of iodinated x-ray contrast media on renal epithelial cells in culture. Invest Radiol 1994; 29(11): 955-62.
[http://dx.doi.org/10.1097/00004424-199411000-00002] [PMID: 7890510]
[41]
Zager RA, Johnson AC, Hanson SY. Radiographic contrast media-induced tubular injury: evaluation of oxidant stress and plasma membrane integrity. Kidney Int 2003; 64(1): 128-39.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00059.x] [PMID: 12787403]
[42]
Fähling M, Seeliger E, Patzak A, Persson PB. Understanding and preventing contrast-induced acute kidney injury. Nat Rev Nephrol 2017; 13(3): 169-80.
[http://dx.doi.org/10.1038/nrneph.2016.196] [PMID: 28138128]
[43]
Andreucci M, Fuiano G, Presta P, et al. Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells. Biochem Pharmacol 2006; 72(10): 1334-42.
[http://dx.doi.org/10.1016/j.bcp.2006.08.008] [PMID: 16989777]
[44]
Yano T, Itoh Y, Kubota T, Sendo T, Oishi R. A prostacyclin analog beraprost sodium attenuates radiocontrast media-induced LLC-PK1 cells injury. Kidney Int 2004; 65(5): 1654-63.
[http://dx.doi.org/10.1111/j.1523-1755.2004.00575.x] [PMID: 15086904]
[45]
Sumimura T, Sendo T, Itoh Y, et al. Calcium-dependent injury of human microvascular endothelial cells induced by a variety of iodinated radiographic contrast media. Invest Radiol 2003; 38(6): 366-74.
[http://dx.doi.org/10.1097/01.RLI.0000066249.29279.1e] [PMID: 12908704]
[46]
Inagi R, Ishimoto Y, Nangaku M. Proteostasis in endoplasmic reticulum--new mechanisms in kidney disease. Nat Rev Nephrol 2014; 10(7): 369-78.
[http://dx.doi.org/10.1038/nrneph.2014.67] [PMID: 24752014]
[47]
Wu CT, Sheu ML, Tsai KS, Weng TI, Chiang CK, Liu SH. The role of endoplasmic reticulum stress-related unfolded protein response in the radiocontrast medium-induced renal tubular cell injury. Toxicol Sci 2010; 114(2): 295-301.
[http://dx.doi.org/10.1093/toxsci/kfq006] [PMID: 20071420]
[48]
Gospos C, Freudenberg N, Staubesand J, Mathias K, Papacharlampos X. The effect of contrast media on the aortic endothelium of rats. Radiology 1983; 147(3): 685-8.
[http://dx.doi.org/10.1148/radiology.147.3.6844605] [PMID: 6844605]
[49]
Romano G, Briguori C, Quintavalle C, et al. Contrast agents and renal cell apoptosis. Eur Heart J 2008; 29(20): 2569-76.
[http://dx.doi.org/10.1093/eurheartj/ehn197] [PMID: 18468994]
[50]
Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med 2018; 378(7): 603-14.
[http://dx.doi.org/10.1056/NEJMoa1710933] [PMID: 29130810]
[51]
Katzberg RW. Contrast medium-induced nephrotoxicity: which pathway? Radiology 2005; 235(3): 752-5.
[http://dx.doi.org/10.1148/radiol.2353041865] [PMID: 15914474]
[52]
Pisani A, Riccio E, Andreucci M, et al. Role of reactive oxygen species in pathogenesis of radiocontrast-induced nephropathy. BioMed Res Int 2013; 2013 868321
[http://dx.doi.org/10.1155/2013/868321] [PMID: 24459673]
[53]
Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007; 87(1): 315-424.
[http://dx.doi.org/10.1152/physrev.00029.2006] [PMID: 17237348]
[54]
Giaccia AJ, Simon MC, Johnson R. The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes Dev 2004; 18(18): 2183-94.
[http://dx.doi.org/10.1101/gad.1243304] [PMID: 15371333]
[55]
Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2009; 2: 2.
[http://dx.doi.org/10.1186/1755-8794-2-2] [PMID: 19133145]
[56]
Pisani A, Sabbatini M, Riccio E, et al. Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury. Clin Exp Nephrol 2014; 18(3): 424-31.
[PMID: 23807430]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 25
ISSUE: 44
Year: 2019
Page: [4642 - 4647]
Pages: 6
DOI: 10.2174/1381612825666191210152944
Price: $65

Article Metrics

PDF: 28
HTML: 3