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University of Wisconsin Hospital and Clinics
Guidelines for the Prevention of Contrast-Induced Nephropathy in Adults
Last Updated by: Molly Thompson, PharmD; Cindy Gaston, PharmD
Coordination: Lee Vermeulen, MS, RPh, FCCP, Director CDP
Reviewed by: Michael Hofmann, MD; Giorgio Gimelli, MD; Maryl Johnson, MD; Girma Tefera, MD;
Sharon Bartosh, MD; Cheryl Sanchez, MD; Myron Pozniak, MD; Christine Griffin, RN; Karna Boquet, RN;
Susan Schroeder, RN, MSN; Mary Randel, RN, ACNP; Gwen Klinkner, RN, MSN; Jennifer Grice,
Approved by P&T Committee: April 2006
Last Reviewed by P & T: December 2008
Next Scheduled Review Date: December 2010
These clinical guidelines were designed to assist clinicians by providing a framework for the identification,
evaluation and treatment options available to reduce the risk of contrast-induced kidney failure in high risk
populations. They were developed by reviewing and incorporating the most current evidenced-based
literature available. These guidelines are not intended to replace a clinician’s judgment or to establish a
The intravascular administration of contrast media can lead to acute kidney injury. Contrast agents
induce kidney injury and reduce kidney function by altering hemodynamics and by direct toxic effects on
kidney cells. Even small changes in kidney function have been associated with increased morbidity and
mortality, making prevention of contrast-induced nephropathy (CIN) of paramount importance. Clinical
trials have defined CIN as an increase in serum creatinine by 25% or 0.5 mg/dL within 2-5 days after
contrast. The mechanism by which contrast induced kidney injury occurs is not well understood.
Preliminary evidence in animals suggest two theories.1
• Vasoconstriction – In animal studies the infusion of contrast media resulted in a transient
increase in perfusion, followed by an abrupt, sharp and prolonged decrease in blood flow. In some studies completed on humans, the reduction in blood flow with contrast media did not occur suggesting that the functional redistribution of intrarenal blood flow leads to medullary ischemia and tubular damage. There is evidence that diabetes mellitus and congestive heart failure disorders are associated with impaired nitric oxide generation which could contribute to increased susceptibility to contrast agents.
• Tubular Injury – Direct tubular injury may occur as a consequence of proximal tubule cell
exposure to hyperosmolar contrast media.
It is estimated that three to five percent of hospitalized patients develop acute kidney injury. One of the most common etiologies is the administration of intravenous (IV) or intra-arterial contrast media. The incidence of CIN is highly dependent on clinical characteristics and reported ranges are near zero percent in low risk patients to over fifty percent in high-risk patients.2-6 The administration of any contrast agent lead to acute kidney injury. In addition, the FDA issued an alert in 2008 about the risk of nephrogenic systemic fibrosis (NSF) associated with the use of gadolinium-based contrast agents and required that a black box warning be added to the package labeling of these products.7 Gadolinium-based contrast agents are FDA-approved for magnetic resonance imaging (MRI) but are sometime used off-label for magnetic resonance angiography as well. These products have been implicated with increasing the risk of NSF in patients with acute or chronic severe renal function impairment (glomerular filtration rate less than 30 mL/min per 1.73m2) or in patients with acute renal function impairment of any severity because of the hepatorenal syndrome or in those in the perioperative liver transplantation period. In these patient populations, the FDA recommends the avoidance of gadolinium-based contrast agents unless the diagnostic information is essential and not available with noncontrast enhanced MRI. NSF may result in fatal or debilitating systemic fibrosis affecting the skin and
connective tissues throughout the body. The FDA warns that the recommended dose of gadolinium-based contrast agents should not be exceeded and that a sufficient period of time be allowed for elimination of the agent from the body prior to any readministration. This guideline will summarize the principal risk factors for CIN along with evidence-based preventive strategies. There are several studies and meta-analyses on treatment modalities for the prevention of CIN, however the treatment doses, administration methods, and outcomes are variable between studies. Given the lack of consistency between studies, these guidelines should be viewed as recommendations.
B. Evaluation of kidney function
1.0 The standard for defining kidney function will be the use of the estimated glomerular filtration
rate (eGFR). See Appendix A. Note: eGFR cannot accurately predict acute changes in kidney
2.0 Spot urine tests are recommended on all diabetic patients to assess for proteinuria.
3.0 Assessment of the BUN and creatinine should be completed within two weeks prior to the
C. Risk assessment
1.0 Specific risk factors associated with increased risk of CIN2,3,7-13
1.1 Stage 4 chronic kidney disease (CKD)- eGFR < 30 mL/min/1.73 meters squared
With lesser stages of CKD, the incidence of CIN approximates 5-10%2-4
1.2 Proteinuria- greater than 3 grams of protein per day 1.3 Diabetes mellitus (DM) - diabetic nephropathy
Combination of DM and CKD increases risk to 10-50%2,4-6
At risk patients include those with congestive heart failure, hepato-renal
syndrome and ascites. In these clinical situations, decreased effective
circulating volume and reduced kidney perfusion potentiate vasoconstriction
1.5 High volume contrast administration or multiple sequential procedures with contrast
1.6 Concomitant administration of drugs that alter kidney hemodynamics 1.7 Hyponatremia 1.8 Hypoalbuminuria 1.9 Advanced age 1.10 Multiple myeloma 1.11 Peripheral vascular disease 1.12 Congestive heart failure 1.13 Myocardial infarction less than 24 hours before procedure
D. Patient management
1.1 All high risk patients should have a renal function assessment to determine if they meet
the inclusion criteria for bicarbonate hydration. Patients meeting the inclusion criteria should receive bicarbonate hydration and post-contrast management as outlined below.
Patient selection criteria: 18.104.22.168 Previously documented contrast-induced acute kidney injury and/or
22.214.171.124 eGFR less than 30 mL/min/1.73 meters squared 126.96.36.199 Evidence of diabetic nephropathy 188.8.131.52 Proteinuria greater than 3 grams
184.108.40.206 Uncontrolled hypertension with a systolic blood pressure > 160
mmHg or diastolic blood pressure > 100 mmHg
220.127.116.11 Emergency procedures 18.104.22.168 Cardiomyopathy or congestive heart failure patients at risk for fluid
overload. Confer with CHF Staff or consult service for pre-clearance.
Obtain a serum creatinine no more than 2 weeks prior to planned contrast
Perform random spot urine for protein and creatinine on all diabetic patients to assess for proteinuria.
ordering a procedure that requires contrast media need to
complete a review of patient medications and identify potentially nephrotoxic medications with consideration of holding such agents such as NSAIDS and diuretics.
All patients receiving metformin will have this medication held the morning of contrast administration and for 48 hours after contrast administration
2.1 Published literature supports the use of iso-osmolal nonionic contrast media14-17 and
2.2 Hydration solutions: In prophylactic hydration the most efficacious anion for sodium is
bicarbonate. Alkalizing the renal tubular fluid with bicarbonate may reduce injury19-23.
2.3 N-acetylcysteine: In trials evaluating n-acetylcysteine for the prevention of CIN, the
results have been inconsistent and do not at this point support the standard use of n-acetylcysteine for all at-risk patients.24-48
Iso-osmolal nonionic contrast media12-15 (e.g., iodixanol)
Solution: dextrose 5% in water 1000 mL with sodium bicarbonate 200 mEq, total volume 1250 mL, final concentration sodium bicarbonate 160 mEq/Liter
Infuse sodium bicarbonate solution in the following manner15: 22.214.171.124 Initiate bolus infusion 3 mL/kg/hr (max 330 mL/hr) for ONE HOUR
126.96.36.199 Following the bolus- reduce rate to 1mL/kg/hr (max 110 mL/hr)
188.8.131.52 Post-Procedure- run fluid at 1 mL/kg/hr (max 110 mL/hr) for SIX
HOURS after the first contrast administration.
Table 1. Infusion Rate of Sodium Bicarbonate Hydration Bolus
Table 2. Infusion Rate of Sodium Bicarbonate Hydration Infusion
3.3 N-acetylcysteine administration- OPTIONAL.
Though level A evidence is lacking and results from clinical trails are conflicting, practitioners may wish to administer n-acetylcysteine prior to emergent radiologic procedures that require contrast in at-risk individuals as defined.
N-acetylcysteine 800 mg, 2 doses ORALLY at 1600 and 2000 the day before contrast administration. Mix with 30 mL cola to disguise the taste. In emergency procedures, 2 doses orally may be given 4-6 hours apart prior to contrast.
4.0 Post contrast administration management:
If inpatient, assess serum creatinine and re-calculate the eGFR on the morning following contrast administration and in 3 days after administration of contrast agent.
If outpatient, assess serum creatinine 3 days after administration of contrast agent.
All patients who received n-acetylcysteine pre-contrast administration should have an additional two- 800 mg doses ORALLY six hours apart following
administration of contrast as directed above.
1. UWHC Laboratory calculates eGFR on outpatients with a measured serum creatinine using the
MDRD equation: GFR (mL/min/1.73m2) = 175 x (SCr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if black). If requested it can also be reported for inpatients.
Assess patient risk factors
- GFR < 30 mL/min/1.73m2- Stage 4 chronic kidney disease- Proteinuria > 3 grams/day- Previously documented contrast-induced decline in kidney function- Diabetes mellitus - diabetic nephropathy- Intravascular volume depletion - CHF, hepto-renal syndrome- High volume contrast administration- Multiple sequential procedures with contrast media- Concomitant administration of drugs that alter kidney hemodynamics- Hyponatremia- Hypoalbuminuria- Increased age- Multiple myeloma- Perpheral vascular disease- Congestive heart failure- Mycardial infarction less than 24 hours prior to procedure
Perform original test.
Implement additional prophylactic measure.
- Administer intravenous sodium bicarbonate- Limit contrast dose- Use iso-osmolal contrast
- Hold potentially nephrotoxic medications prior to
contrast- Administer N-acetylcysteine-optional- Monitor creatinine and eGFR post contrast
Perform alternative test. No additional prophlyactic measures required.
1. Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium induced nephropathy. Kidney Int
2. Parfrey, PS, Griffiths, SM, Barrett, BJ, et al. Contrast material-induced renal failure in patients with
diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med
3. Rudnick, MR, Goldfarb, S, Wexler, L, et al. Nephrotoxicity of ionic and nonionic contrast media in
1196 patients: A randomized trial. Kidney Int
4. Barrett, BJ, Parfrey, PS, Vavasour, HM, et al. Contrast nephropathy in patients with impaired renal
function: high versus low osmolar media. Kidney Int
5. Manske, CL, Sprafka, JM, Strong, JH, Wang, Y. Contrast nephropathy in azotemic diabetic patients
undergoing coronary angiography. Am J Med
6. Weinrauch, LA, Healy, RW, Leland, OS, et al. Coronary angiography and acute renal failure in
diabetic nephropathy. Ann Intern Med
7. U.S. Food and Drug Administration. Information for Healthcare Professionals: Gadolinium-Based
Contrast Agents for Magnetic Resonance Imaging. Available at: http://www.fda.gov/cder/drug/InfoSheets/HCP/gcca_200705.htm. Accessed 12/19/08.
8. Davidson, CJ, Hlatky, M, Morris, KG, et al. Cardiovascular and renal toxicity of a nonionic
radiographic contrast agent after cardiac catheterization. A prospective trial. Ann Intern Med
9. 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
10. Cigarroa, RG, Lange, RA, Williams, RH, Hillis, LD. Dosing of contrast material to prevent contrast
nephropathy in patients with renal disease. Am J Med
11. Lautin, EM, Freeman, NJ, Schoenfeld, AH, et al. Radiocontrast-associated renal dysfunction:
Incidence and risk factors. Am J Roentgenol
12. Barrett, BJ. Contrast nephrotoxicity. J Am Soc Nephrol
1994; 5:125-137. 13. Bartholomew BA, Harjai KJ, Dukkipati S, et al. Impact of nephropathy after percutaneous coronary
intervention and a method for risk stratification. Am J Cardiol
. 2004; 93:1515-1519.
14. Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after
percutaneous coronary intervention Circulation.
15. Chalmers, N, Jackson, RW. Comparison of iodixanol and iohexol in renal impairment. Br J Radiol
16. Aspelin, P, Aubry, P, Fransson, SG, et al. Nephrotoxic effects in high-risk patients undergoing
angiography. N Engl J Med
17. Jo SH, Youn TJ, Koo BK, et al. Renal toxicity evaluation and comparison between visipaque
(iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial. J Am Coll Cardiol
. 2006; 48:924-930.
18. Solomon RJ, Natarajn MK, Doucet S, et al. Cardiac angiography in renally impaired patients (CARE)
study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation
. 2007; 115:3189-3196.
19. Mueller, C, Buerkle, G, Buettner, HJ, et al. Prevention of contrast media-associated nephropathy:
randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med
20. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium
bicarbonate: a randomized controlled trial. JAMA
21. Brar SS, Shen AY, Jorgenson MB, et al. Sodium bicarbonate vs sodium chloride for the prevention
of contrast medium-induced nephropathy in patients undergoing coronary angiography. JAMA
. 2008; 300:1038-1046.
22. Recio-Mayoral A, Chaparro M, Prado B, et al. The reno-protective effect of hydration with sodium
bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention. J Am Coll Cardiol
. 2007; 49:1283-1288.
23. Briguori C, Airoldi F, D’Andrea D, et al. Renal insufficiency following contrast media administration
trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation
24. Masuda M, Yamada T, Mine T, et al. Comparison of usefulness of sodium bicarbonate versus
sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure. Am J Cardiol
. 2007; 100:781-786.
25. Gomes VO, Poli de Figueredo CE, Caramori P, et al. N-acetylcysteine does not prevent contrast
induced nephropathy after cardiac catheterisation with an ionic low osmolality contrast medium: a multicentre clinical trial. Heart
26. Webb JG, Pate GE, Humphries KH, et al. A randomized controlled trial of intravenous N-
acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: lack of effect. Am Heart J
27. Rashid ST, Salman M, Myint F, et al. Prevention of contrast-induced nephropathy in vascular patients
undergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine. J Vasc Surg
28. Ochoa A, Pellizzon G, Addala S, et al. Abbreviated dosing of N-acetylcysteine prevents contrast-
induced nephropathy after elective and urgent coronary angiography and intervention. J Interv Cardiol
29. Miner SES, Dzavik V, Nguyen-Ho P, et al. N-acetylcysteine reduces contrast-associated nephropathy
but not clinical events during long-term follow-up. Am Heart J
30. Hoffmann U, Fischereder M, Kruger B, Drobnik W, Kramer BK. The value of N-acetylcysteine in the
prevention of radiocontrast agent-induced nephropathy seems questionable. J Am Soc Nephrol
31. Goldenberg I, Shechter M, Matetzky S, et al. Oral acetylcysteine as an adjunct to saline hydration for
the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlled trial and review of the current literature. Eur Heart J
32. Fung JWH, Szeto CC, Chan WWM, et al. Effect of N-acetylcysteine for prevention of contrast
nephropathy in patients with moderate to severe renal insufficiency: a randomized trial. Am J Kidney Dis
33. Drager LF, Andrade L, Barros de Toledo JF, Laurindo FRM, Machado Cesar LA, Seguro AC. Renal
effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury. Nephrol Dial Transplant
34. Briguori C, Colombo A, Violante A, et al. Standard vs double dose of N-acetylcysteine to prevent
contrast agent associated nephrotoxicity. Eur Heart J
35. Briguori C, Colombo A, Airoldi F, et al. N-Acetylcysteine versus fenoldopam mesylate to prevent
contrast agent-associated nephrotoxicity. J Am Coll Cardiol
36. Oldemeyer JB, Biddle WP, Wurdeman RL, Mooss AN, Cichowski E, Hilleman DE. Acetylcysteine in
the prevention of contrast-induced nephropathy after coronary angiography. Am Heart J
37. MacNeill BD, Harding SA, Bazari H, et al. Prophylaxis of contrast-induced nephropathy in patients
undergoing coronary angiography. Catheter Cardiovasc Interv
38. Kefer JM, Hanet CE, Boitte S, Wilmotte L, De Kock M. Acetylcysteine, coronary procedure and
prevention of contrast-induced worsening of renal function: which benefit for which patient? Acta Cardiol
39. Kay J, Chow WH, Chan TM, et al. Acetylcysteine for prevention of acute deterioration of renal
function following elective coronary angiography and intervention: a randomized controlled trial. JAMA
40. Boccalandro F, Amhad M, Smalling RW, Sdringola S. Oral acetylcysteine does not protect renal
function from moderate to high doses of intravenous radiographic contrast. Catheter Cardiovasc Interv
41. Baker CSR, Wragg A, Kumar S, De Palma R, Baker LRI, Knight CJ. A rapid protocol for the
prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol
42. Shyu KG, Cheng JJ, Kuan P. Acetylcysteine protects against acute renal damage in patients with
abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol
43. Durham JD, Caputo C, Dokko J, et al. A randomized controlled trial of N-acetylcysteine to prevent
contrast nephropathy in cardiac angiography. Kidney Int
44. Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Acetylcysteine to prevent angiography-related renal
tissue injury (the APART trial). Am J Cardiol
45. Briguori C, Manganelli F, Scarpato P, et al. Acetylcysteine and contrast agent-associated
nephrotoxicity. J Am Coll Cardiol
46. Allaqaband S, Tumuluri R, Malik AM, et al. Prospective randomized study of N-acetylcysteine,
fenoldopam, and saline for prevention of radiocontrast-induced nephropathy. Catheter Cardiovasc Interv
47. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-
contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med
48. Zagler A, Azadpour M, Mercado C, Hennekens CH. N-acetylcysteine and contrast-induced
nephropathy: A meta-analysis of 13 randomized trials. Am Heart J
. 2006; 151:140-145.
49. Marenzi, G. Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in
primary angioplasty. N Eng J Med
. 2006; 354:2773-2782.
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