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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

A. Background/Rationale
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: Previously documented contrast-induced acute kidney injury and/or eGFR less than 30 mL/min/1.73 meters squared Evidence of diabetic nephropathy Proteinuria greater than 3 grams Uncontrolled hypertension with a systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg Emergency procedures 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: Initiate bolus infusion 3 mL/kg/hr (max 330 mL/hr) for ONE HOUR Following the bolus- reduce rate to 1mL/kg/hr (max 110 mL/hr) 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
Weight (Kg)
Weight (Pounds)
Rate (mL/hr)

Table 2. Infusion Rate of Sodium Bicarbonate Hydration Infusion
Weight (Kg)
Weight (Pounds)
Rate (mL/hr)
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.
Appendix A

eGFR Calculator:
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. Appendix B
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.
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