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Case ReportContrast-induced acute kidney injury (CIAKI)

remains a concern for those administering iodin-ated contrast agents and caring for patients who receive contrast media. Since the first case report in 1954,1 research on the pathophysiology of CIAKI helped transform our therapeutic approaches and sharpened our ability to predict who will develop this adverse effect. Multiple approaches for the prevention of CIAKI have been subjected to pro-spective randomized trials because patients who are to receive contrast media are known in advance. For some approaches, multiple trials have been summarized in meta-analyses. However, despite the wealth of studies, few approaches survived the scrutiny of rigorous scientific study. More recently, appreciation for the long-term impact of CIAKI on mortality and progression of kidney disease rein-vigorated our desire to prevent CIAKI and target patients with CIAKI for closer follow-up. In this brief review and update, we will touch on the re-cent studies contributing to our understanding of the pathophysiology of CIAKI, characteristics of patients at high risk for CIAKI, preventative mea-sures for which there is rigorous supportive evi-dence, and the long-term outcomes in those who develop CIAKI.

PathophysiologyCIAKI results from the direct nephrotoxic effects

of contrast on kidney cells and ischemia mediated by alterations in the balance between O2 delivery and O2 consumption in critical parts of the kidney.2 How contrast media alters the balance between O2 delivery and consumption, particularly in vulnera-ble regions of the kidney, was studied using a vari-ety of new techniques. A relatively new finding is that contrast media causes vasoconstriction in the vasa recta, the vessels supplying O2 to the outer medullary region of the kidney where tissue pO2 is already very low. This area of the kidney gets only a small fraction of renal blood flow yet has

the highest consumption of O2 to support active sodium transport.3 The contrast-induced vasocon-striction is mediated in part by the production of reactive oxygen species (ROS), depletion of nitric oxide (NO), and increased sensitivity to angio-tensin II.4,5 Although the demonstration of direct vasoconstriction was observed in isolated vasa recta vessels, contrast medium were also shown to decrease the tissue level of oxygen in the outer medulla of intact animals as determined by blood oxygen level dependent magnetic resonance imag-ing (BOLD-MRI).6 These two observations rein-force the central role of ischemia in causing CIA-KI. Additional mechanisms may also be at work. Katzberg et al performed non-contrast computed tomography (CT) of the abdomen 24 hours after patients underwent either coronary angiography or liver chemoembolization using contrast media. They observed segmental renal cortical retention of contrast consistent with either small embolic events or regional vasospasm.7

Risk AssessmentA number of risk models have been developed

to identify patients who are likely to develop CIA-KI.8 In addition to the well recognized role of base-line kidney function, presence of congestive heart failure, and dose of contrast medium, additional risk factors include anemia,9 glycemic control,10-12 and hyperuricemia.13 Adjusted for baseline kidney function, the volume of contrast administered (vol-ume/GFR or volume/creatinine) provides enhanced discriminatory value for predicting CIAKI.14,15 New risk factor tools have been developed for use before patients are exposed to contrast.16,17 The risk of CIAKI may be different in patients who receive in-tra-arterial vs. intravenous (IV) contrast although this remains somewhat controversial.18-20 A me-ta-analysis of 40 trials found an incidence follow-ing intravenous contrast administration of 6.5%.21 In general, risk of CIAKI following intravenous administration of contrast is seen only in patients

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,™ Supplement A to the Journal of Invasive Cardiology, September 2014

Contrast-Induced Nephropathy: What has Changed?

Richard Solomon, MD, FASN, FACP

2

with eGFR <45 mL/min while patients with eGFR <60 mL/min are considered high-risk for CIAKI following intra-arterial administration of contrast. The risk with IV contrast is also greatest in hospi-talized patients compared to outpatients, probably because inpatient status is a marker of other co-morbidities that put the kidney at risk for any cause of acute kidney injury.22 This probably explains the observations that the incidence of CIAKI is sim-ilar in hospitalized patients undergoing non-con-trast compared with contrast enhanced CT until you consider patients with low GFRs.23,24 Finally, others have used bioimpedance measurements to identify patients who are most at risk of CIAKI.25 Patients in whom interstitial body water is lowest before contrast exposure are at highest risk for de-velopment of CIAKI. This approach could be used to guide preventative therapy.

PreventionHydration with sodium-containing solutions remains

the mainstay of current guidelines. A comprehensive re-view of fluid-based preventative therapy can be found in Interventional Cardiology Clinics.26 The review con-cluded that for high-risk patients, sodium-containing fluids should be administered 2-4 hours prior to contrast exposure and for 4-6 hours post-exposure. For patients undergoing coronary angiography, the use of left ven-tricular end-diastolic pressure (LVEDP) to guide fluid therapy has been reported to reduce the incidence of CIAKI.27 Patients with lower LVEDP can usually toler-ate more fluid at a faster rate, and the amount of fluid given (and the resulting urine output) may be the key determinant of the benefit of fluid therapy. Enough flu-id should be administered to provoke a vigorous urine

output (>150 mL/hr).28 In this regard, oral ingestion of water also contributes to increasing urine output.29

The use of bicarbonate in-stead of chloride-containing solutions may offer additional advantages based upon recent meta-analyses of trials (Figure 1) involving patients undergoing intra-arterial contrast primarily for cardiac studies.30,31 Howev-er, evidence supporting the use of a bicarbonate rapid infusion in high-risk patients undergoing CT has also been reported.32

The use of antioxidants such as N-acetylcysteine (NAC) have not been supported by recent

large multicenter trials such as the Acetylcysteine for Contrast-Induced Nephropathy (ACT) trial.33 A sub-study of the ACT trial also found no benefit in patients with diabetes.34 The Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial with an expected enrollment of ~8000 subjects, comparing NAC and bicarbonate to control and combined ther-apy, has just commenced and should provide definitive answers to the role of bicarbonate and NAC.35

The importance of a vigorous urine output is also supported by studies of forced diuresis with matching volume replacement using the RenalGuard system.36 This system permits high urine flow rates without risk-ing either volume overload or depletion. Urine output increases to >300 mL/h within about 45 minutes and remains between 300-600 mL/hr for the next 4-5 hours

Figure 1. A Forrest plot from the most recent meta-analysis supporting a benefit of bicarbonate in the prevention of CIAKI.31

Adapted from Jang JS, et al.

Figure 2. The mean urine flows in a trial using the RenalGuard system.Adapted from Briguori C, et al.

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following a bolus of 250 mL saline and a small dose of furosemide (<0.5 mg/kg) (Figure 2). Two separate Italian multicenter trials involving high-risk patients undergoing coronary angiography and PCI demon-strated a reduction in CIAKI.37,38 A third multicenter trial is currently underway in the US (evaluation of RenalGuard system to reduce the incidence of contrast induced nephropathy in at-risk patients [CIN-RG], NCT 01456013) as well as additional trials in Europe.

Recently, a number of novel approaches to prevention have also been reported. Remote ischemic preconditioning has been applied in patients un-dergoing cardiopulmonary bypass as well as coronary an-giography.39 This technique in-volves repetitive cycles of arm or leg ischemia prior to con-trast exposure. The ischemia is produced by inflation of a blood pressure cuff well above systolic pressure for 5 min-utes, interrupted by 5 minutes of recovery. Remote ischemic preconditioning was shown to reduce the incidence of CIAKI in a small trial of patients.40 Multiple trials investigated the use of statins for prevention of CIAKI. Over 15 prospective randomized trials have been conducted with statins using

various doses, specific agents, and patient groups. A recent meta-analysis concluded that statins were effective in reducing the incidence of CIAKI (Figure 3).41 The benefit of statin therapy does not appear to be related to reduction in lipid levels and subgroup analyses suggest that its effect is robust across diverse patient populations. Finally, the use of automated in-jectors has been found to reduce the total amount of contrast administered and the incidence of CIAKI in recent meta-analyses.42,43

The impact of different classes of contrast media has also been updated using a new meta-analysis technique. Previous classic meta-analyses found no differences in the incidence of CIAKI among isos-molar and low osmolar contrast agents.44,45 Using the network meta-analysis technique, an approach that incorporates indirect as well as direct com-parisons among different contrast agents, 42 trials involving >10,000 patients were analyzed. Isosmolar and low osmolar contrast were again found to be equally effective in minimizing CIAKI. However, there were two exceptions noted. Ioxaglate (an ionic low osmolar contrast medium) and iohexol (a non-ionic low osmolar contrast medium) were each associated with a higher incidence of CIAKI compared to other low osmolar and isosmolar con-trast media (Figure 4).46

Finally, using institutional protocols to determine who is at risk and how they should be treated for pre-vention of CIAKI was shown to lower the overall rate

Figure 3. A Forrest plot from a recent meta-analysis supporting a benefit of statin administration for the prevention of CIAKI.41

Figure 4. A network meta-analysis of contrast media and the risk of CIAKI. The size of the circle corresponds to the probability of its being the best prevention for CIAKI.46

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of CIAKI.47 However, even with national guidelines, many patients at risk are not receiving adequate prophylaxis.48 A recent survey of interventional cardiologists also found that <50% use a written practice-wide protocol.49

Consequences of CIAKILong-term follow-up studies of patients who

develop CIAKI have consistently shown higher mortality and worse kidney function compared with those who do not develop CIAKI.50,51 There is controversy regarding whether CIAKI causes these adverse outcomes or is a marker for comorbidities that in turn cause the adverse outcomes. Regardless of whether CIAKI is a cause or marker for adverse outcomes, the recognition of the consequences of CIAKI led most new trials to incorporate mortal-ity, need for dialysis, and sustained decrements in kidney function as primary outcomes.

ConclusionsPrevention of CIAKI remains an unrealized goal.

With an aging population and increased use of imag-ing techniques involving contrast for both diagnosis and treatment, CIAKI will continue to be a major con-cern in the care of these patients. Strategies to identify high-risk patients, reduce the amount of contrast used, and provide evidence-based approaches to prevention offer the best approach for patient care.

References1. Bartels ED, Brun GC, Gammeltof A, Gjorup LA. Acute anuria fol-

lowing intravenous pyelography in a patient with myelomatosis. Acta Medica Scandinavica. 1954;150(4):297-302.

2. Heyman SN, Rosen S, Khamaisi M, Idee JM, Rosenberger C. Reac-tive oxygen species and the pathogenesis of radiocontrast-induced nephropathy. Invest Radiol. 2010;45(4):188-195.

3. Heyman SN, Brezis M, Reubinoff CA, et al. Acute renal fail-ure with selective medullary injury in the rat. J Clin Invest. 1988;82(2):401-412.

4. 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.

5. Sendeski M, Patzak A, Persson PB. Constriction of the vasa recta, the vessels supplying the area at risk for acute kidney injury, by four different iodinated contrast media, evaluating ionic, nonionic, mo-nomeric and dimeric agents. Invest Radiol. 2010;45(8):453-457.

6. Li LP, Franklin T, Du H, et al. Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose. J Magn Reson Imaging. 2012;36(5):1162-1167.

7. Katzberg RW, Monsky WL, Prionas ND, et al. Persistent CT nephrograms following cardiac catheterisation and intervention: initial observations. Insights Imaging. 2012;3(1):49-60.

8. Tziakas D, Chalikias G, Stakos D, et al. Validation of a new risk score to predict contrast-induced nephropathy after percutaneous coronary intervention. Am J Cardiol. 2014;113(9):1487-1493.

9. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004;44(7):1393-1399.

10. Marenzi G, De Metrio M, Rubino M, et al. Acute hy-perglycemia and contrast-induced nephropathy in pri-mary percutaneous coronary intervention. Am Heart J. 2010;160(6):1170-1177.

11. Stolker JM, McCullough PA, Rao S, et al. Pre-procedural glu-cose levels and the risk for contrast-induced acute kidney injury in patients undergoing coronary angiography. J Am Coll Cardiol. 2010;55(14):1433-1440.

12. Toprak O, Cirit M, Yesil M, et al. Impact of diabetic and pre-di-abetic state on development of contrast-induced nephropathy in patients with chronic kidney disease. Nephrol Dial Transplant. 2007;22(3):819-826.

13. Okino S, Fukuzawa S, Inagaki M, et al. Hyperuricemia as a risk factor for progressive renal insufficiency after coronary interven-tion in patients with chronic kidney disease. Cardiovasc Interv Ther. 2010;25(2):105-111.

14. Mager A, Vaknin Assa H, Lev EI, Bental T, Assali A, Kornows-ki R. The ratio of contrast volume to glomerular filtration rate predicts outcomes after percutaneous coronary intervention for ST-segment elevation acute myocardial infarction. Catheter Car-diovasc Interv. 2011;78(2):198-201.

15. Brown JR, Robb JF, Block CA, et al. Does safe dosing of iodinated contrast prevent contrast-induced acute kidney injury? Circ Car-diovasc Interv. 2010;3(4):346-350.

16. Gurm HS, Seth M, Kooiman J, Share D. A novel tool for reliable and accurate prediction of renal complications in patients under-going percutaneous coronary intervention. J Am Coll Cardiol. 2013;61(22):2242-2248.

17. Singh M, Rihal CS, Lennon RJ, Spertus J, Rumsfeld JS, Holmes DR Jr. Bedside estimation of risk from percutaneous coronary intervention: the new Mayo Clinic risk scores. Mayo Clin Proc. 2007;82(6):701-708.

18. Karlsberg RP, Dohad SY, Sheng R; for the Iodixanol Peripheral Computed Tomographic Angiography Study Investigator Panel. Contrast medium-induced acute kidney injury: comparison of in-travenous and intraarterial administration of iodinated contrast medium. J Vasc Interv Radiol. 2011;22(8):1159-1165.

19. Kooiman J, Le Haen PA, Gezgin G, et al. Contrast-induced acute kidney injury and clinical outcomes after intra-arterial and intra-venous contrast administration: risk comparison adjusted for pa-tient characteristics by design. Am Heart J. 2013;165(5):793-799.

20. Nyman U, Almen T, Jacobsson B, Aspelin P. Are intravenous in-jections of contrast media really less nephrotoxic than intra-arte-rial injections? Eur Radiol. 2012;22(6):1366-1371.

21. Kooiman J, Pasha SM, Zondag W, et al. Meta-analysis: serum creatinine changes following contrast enhanced CT imaging. Eur J Radiol. 2012;81(10):2554-2561.

22. Weisbord S, Mor MK, Resnick AL, et al. Incidence and outcomes of contrast-induced AKI following computed tomography. Clin J Am Soc Nephrol. 2008;3(5):1274-1281.

23. Davenport MS, Khalatbari S, Dillman JR, Cohan RH, Caoili EM, Ellis JH. Contrast material-induced nephrotoxicity and in-travenous low-osmolality iodinated contrast material. Radiology. 2013;267(1):94-105.

24. McDonald JS, McDonald RJ, Comin J, et al. Frequency of acute kidney injury following intravenous contrast medium ad-ministration: a systematic review and meta-analysis. Radiology. 2013;267(1):119-128.

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25. Maioli M, Toso A, Leoncini M, et al. Pre-procedural bioimpedance vectorial analysis of fluid status and prediction of contrast-induced acute kidney injury. J Am Coll Cardiol. 2014;63(14):1387-1394.

26. Rojkowskiy I, Solomon R. Intravenous and oral hydration: ap-proaches, principles, and differing regimes. Intervent Cardiol Clin. 2014;3(3):393-404.

27. Brar SS, Aharonian V, Mansukhani P, et al. Haemodynamic-guid-ed fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. Lancet. 2014;383(9931):1814-1823.

28. Stevens MA, McCullough PA, Tobin K, et al. A prospective ran-domized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Preven-tion of Radiocontrast Induced Nephropathy Clinical Evaluation. J Am Coll Cardiol. 1999;33(2):403-411.

29. Hiremath W, Akbari A, Shabana W, Fergusson DA, Knoll GA. Prevention of contrast-induced acute kidney injury: is simple oral hydration similar to intravenous? A systematic review of the evi-dence. PLos ONE. 2013;8(3):e60009.

30. Wiedermann CJ, Joannidis M. Increasing evidence base for sodi-um bicarbonate therapy to prevent contrast media-induced acute kidney injury: little role of unpublished studies. Nephrol Dial Transplant. 2010;25(3):650-654.

31. Jang JS, Jin HY, Seo JS, et al. Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney injury – a systematic review and meta-analysis. Circ J. 2012;76(9):2255-2265.

32. Kooiman J, Sijpkens YW, de Vries JP, et al. A randomized com-parison of 1-h sodium bicarbonate hydration versus standard peri-procedural saline hydration in patients with chronic kidney disease undergoing intravenous contrast-enhanced computerized tomography. Nephrol Dial Transplant. 2014;29(5):1029-1036.

33. ACT Investigators. Acetylcysteine for prevention of renal out-comes in patients undergoing coronary and peripheral an-giography: main results from the randomized acetylcysteine for contrast-induced nephropathy trial (ACT). Circulation. 2011;124(11):1250-1259.

34. Berwanger O, Cavalcanti AB, Sousa AM, et al. Acetylcysteine for the prevention of renal outcomes in patients with diabetes mellitus undergoing coronary and peripheral vascular angiography: a sub-study of the acetylcysteine for contrast-induced nephropathy trial. Circ Cardiovasc Interv. 2013;6(2):139-145.

35. Weisbord SD, Gallagher M, Kaufman J, et al. Prevention of con-trast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial. Clin J Am Soc Nephrol. 2013;8(9):1618-1631.

36. Solomon R. Forced diuresis with the RenalGuard system: impact on contrast induced acute kidney injury. J Cardiol. 2014;63(1):9-13.

37. Briguori C, Visconti G, Focaccio A, et al; for the REMEDIAL II Investigators. Renal Insufficiency After Contrast Media Adminis-tration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury. Circulation. 2011;124(11):1260-1269.

38. Marenzi G, Ferrari C, Marana I, et al. Prevention of contrast ne-phropathy by furosemide with matched hydration: the MYTHOS (Induced Diuresis With Matched Hydration Compared to Stan-dard Hydration for Contrast Induced Nephropathy Prevention) trial. JACC Cardiovasc Interv. 2012;5(1):90-97.

39. Bonventre JV. Limb ischemia protects against contrast-induced nephropathy. Circulation. 2012;126(4):384-387.

40. Er F, Nia AM, Dopp H, et al. Ischemic preconditioning for prevention of contrast medium-induced nephropathy:

randomized pilot RenPro trial (Renal Protection Trial). Circulation. 2012;126(3):296-303.

41. Gandhi S, Mosleh W, Abdel-Qadir H, Farkouh ME. Statins and contrast-induced acute kidney injury with coronary angiogra-phy: systematic review and meta-analysis. Am J Med. 2014. [Epub ahead of print]

42. Minsinger KD, Kassis HM, Block CA, Sidhu M, Brown JR. Me-ta-analysis of the effect of automated contrast injection devices versus manual injection and contrast volume on risk of con-trast-induced nephropathy. Am J Cardiol. 2014;113(1):49-53.

43. Gurm HS, Smith D, Share D, et al. Impact of automated contrast injector systems on contrast use and contrast-associated complica-tions in patients undergoing percutaneous coronary interventions. JACC Cardiovasc Interv. 2013;6(4):399-405.

44. Heinrich M, Häberle L, Müller V, Bautz W, Uder M. Nephrotox-icity of iso-osmolar iodixanol compared with nonionic low-osmo-lar contrast media: meta-analysis of randomized controlled trials. Radiology. 2009;250(1):68-86.

45. Reed M, Meier P, Tamhane UU, Welch KB, Moscucci M, Gurm HS. The relative renal safety of iodixanol compared with low-os-molar contrast media: a meta-analysis of randomized controlled trials. JACC Cardiovasc Interv. 2009;2(7):645-654.

46. Biondi-Zoccai G, Lotrionte M, Thomsen HS, et al. Nephropa-thy after administration of iso-osmolar and low-osmolar contrast media: evidence from a network meta-analysis. Int J Cardiol. 2014;172(2):375-380.

47. Brown JR, McCullough PA, Splaine ME, et al; for the Northern New England Cardiovascular Disease Study Group. How do cen-tres begin the process to prevent contrast-induced acute kidney injury: a report from a new regional collaborative. BMJ Qual Saf. 2012;21(1):54-62.

48. Schilp J, de Blok C, Langelaan M, Spreeuwenberg P, Wagner C. Guideline adherence for identification and hydration of high-risk hospital patients for contrast-induced nephropathy. BMC Nephrol. 2014;15(1):2.

49. Mehran R. Survey of interventional cardiologists regarding con-trast induced acute kidney injury. Transcatheter Cardiovascular Therapeutics meeting. San Francisco, 2013.

50. James MT, Tonelli M, Ghali WA, et al; for the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease and Alberta Kidney Disease Network Investigators. Renal outcomes associated with invasive versus conservative management of acute coronary syndrome: propensity matched cohort study. BMJ. 2013;347:f4151.

51. Weisbord SD, Chen H, Stone RA, et al. Associations of in-creases in serum creatinine with mortality and length of hos-pital stay after coronary angiography. J Am Soc Nephrol. 2006;17(10):2871-2877.

In order to complete this activity, please visit the website to

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Overview This Journal-Based Activity for contrast nephropathy re-mains one of the most common causes of acute renal failure in hospitalized patients. At present, there are no strategies that are approved by the US Food and Drug Administration (FDA) for prevention of contrast-induced nephropathy. Newer approaches show promise, but adoption is hampered by increased cost and a contin-ued lack of randomized data to confirm efficacy. Howev-er, studies of intravenous hydration have demonstrated benefit with infusion rates pre- and post-procedure (see article for more detail).

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3. Implement a newly developed protocol to provide sufficient hydration to patients during angiographic procedures and therefore reduce the risk of contrast nephropathy and renal failure in high-risk patients.

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