Identification and Management of Patients at Risk for Contrast-Induced Nephropathy: A Practical Approach

Contrast-induced nephropathy (CIN), or acute kidney injury from an iodinated contrast agent, is an important complication in the use of iodinated contrast media that accounts for a significant number of cases of hospital-acquired acute kidney injury. Contrast-induced nephropathy is defined as a sudden deterioration in renal function after the recent intravascular administration of iodinated contrast medium in the absence of another nephrotoxic event. The most commonly used definition in clinical trials is a rise in serum creatinine of 0.5 mg/dL or a 25% increase from the baseline value, assessed at 48 hours after the procedure. In most cases this normalizes in 7 days to 10 days.

The incidence is <2% in the general population but is much higher in patients with risk factors. It is estimated to be as high as 20% to 30% in older patients with diabetes mellitus, chronic renal insufficiency, and congestive heart failure. Mortality rates of 14% to 34% are associated with CIN and it is the third most common cause of hospital-acquired renal failure (first is medications and second is surgery).¹ 

Pathophysiology

The exact pathophysiology of contrast-induced nephropathy is not known but several theories have been proposed. In the presence of reduced nephron mass (reduced renal reserve), the remaining kidney is vulnerable to injury. Iodinated contrast first results in transient vasodilatation and then prolonged vasoconstriction, which results in ischemic injury. This, in turn, sets off a cascade of events mediated by oxidative injury resulting in depth of renal tubular cells. If enough cells die, there is a detectable rise in serum creatinine. Other factors are also thought to increase risk, such as the duration of time renal cells are exposed to contrast (so high urinary flow rates are thought to be protective), oxidative stress, inflammation, hypotension, microatherotic emboli from catheter exchanges, intra-aortic balloon pump counterpulsation, and bleeding complications.¹

Assessing Risk

There is no universally agreed-upon threshold of glomerular filtration rate (GFR) or creatinine beyond which intravenous contrast should not be given, so various ways to assess individual risk have been proposed which include delineation of risk factors, Risk Score systems and setting of GFR thresholds below which preventative measures are instituted.

The American College of Radiology (ACR) and Canadian Association of Radiologists (CAR) have made recommendations for risk assessment and prevention of CIN.^2, 

American College of Radiology

• Age greater than 60 years
• Renal disease
• Dialysis
• Kidney transplant
• Solitary kidney
• Renal cancer
• Renal surgery
• Hypertension being treated with medication
• Diabetes
• Metformin

Canadian Association of Radiologists

• Age greater than 70 years
• Renal disease
• Kidney transplant
• Solitary kidney
• Hypertension, vascular disease
• Diabetes
• Nephrotoxic drugs
• Sepsis or hypotension
• Dehydration
• Chemotherapy
• HIV
• Collagen vascular
• Native Canadian (First Nation)

Diabetes mellitus is a risk multiplier. Other patient-related risk factors include hypotension, low cardiac output, Class IV congestive heart failure, anemia, and hypoalbuminemia (<35 g/L). There are also procedure-related risk factors, which include multiple contrast media injections within 72 hours, intra-arterial injection site, a high volume of contrast media, and a high osmolality of contrast media. Low-osmolar contrast media (LOCM) poses less risk of CIN and iso-osmolar contrast is lower risk than LOCM.

Prevention

No adjunctive medical or mechanical treatment has been proven efficacious at reducing the risk of acute kidney injury after exposure to iodinated contrast. Prophylactic hemodialysis or hemofiltration has not been validated as an effective strategy. As such the focus is on prevention of CIN. Avoidance or reduction of contrast dose are the best ways to decrease the incidence of CIN. 

Dose of contrast administered and type of contrast are important factors to be considered, with LOCM or iso-osmolar contrast demonstrating decreased risk of CIN. Laskey suggested that as a general rule, the volume of contrast not to exceed twice the GFR.⁴ The ACR and CAR have additional recommendations for those patients at risk. The ACR recommendations are more general. The CAR offers more specific prevention measures.

American College of Radiology Recommendations

• Avoid contrast
• Use lowest dose
• Avoid repeated doses (within 24 hours)
• LOCM (and iso-osmolar preferred)
• Hydration (Lactated Ringer’s or .9% saline) 100mL/hr from 6 to 12 hours prior to 4 to 12 hours post 
• Oral hydration less effective
• Pediatric weight-based doses
• Sodium bicarbonate: conflicting evidence (equivalent to hydration)
• N-acetylcysteine: no recommendation
• Avoid furosemide and mannitol 
• Dialysis: contrast may be administered; urgent dialysis only if massive volumes or cardiac 
• issues²

Canadian Association of Radiologists Recommendations: General Guidelines for GFR <60mL/min

• Avoid dehydration 
• Consider alternate imaging studies not requiring contrast medium 
• Minimize contrast medium volume 
• Avoid repeat iodinated contrast studies especially within 48 hours 
• Use LOCM or iso-osmolar nonionic contrast
• Mild to Moderate Risk of CIN: Estimated GFR (eGFR) <45 mL/min and intravenous contrast administration
• Intravenous hydration 
• Avoid dehydration (oral fluids if intravenous hydration impractical) 
• Follow-up serum creatinine and eGFR in 48 to 72 hours 
• Moderate to High Risk of CIN: eGFR < 60 mL/min and IA contrast administration OR any eGFR w/ acute illness, unstable renal function or inpatients
• Hold nephrotoxic drugs (especially NSAIDs and diuretics)
• Hydrate with intravenous NACl or NaHCO₃ 
• Consider N-acetylcysteine
• Follow-up serum creatinine and eGFR in 48 to 72 hours

The University of Kentucky offers specific hydration protocol guidelines.⁵ 

Conclusion

Contrast-induced nephropathy remains a frequent source of acute renal failure and is associated with increased morbidity and mortality. Chronic renal insufficiency, diabetes, dehydration, anemia, and other risk factors predispose patients to contrast-induced renal failure. A GFR of <60 mL/min is a threshold where CIN begins to occur. Reduced contrast dose and choice of agent is most important to minimize risk. This can be accomplished by selecting LOCM or iso-osmolar contrast. Contrast dilution may be employed to further decrease contrast dose.

Preprocedural hydration is a key prevention measure. Other medical therapies to prevent CIN remain controversial. Adoption of a system-wide, approved hospital policy is an important way to minimize CIN risk.

Editor’s note: This article underwent peer review by one or more members of the Interventional Oncology 360 editorial board. 

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports no disclosures related to the content of this manuscript. 

Address for correspondence: Author queries may be directed by email to Ana Echenique, MD, at aecheniq@mac.com.

Recommended citation: Echenique A. Identification and management of patients at risk for contrast-induced nephropathy: a practical approach. Intervent Oncol 360. 2014;2(12):E88-E91.

References

1.McCullough PA. Contrast-Induced Acute Kidney Injury. J Am Coll Cardiol. 2008;51(15):1419-1428.

2.American College of Radiology. Manual on Contrast Media Version 5. 2004; Reston, VA: Author.

3.Owen RJ, Hiremath S, Myers A, Fraser-Hill M, Barrett B. Consensus Guidelines for the Prevention of Contrast Induced Nephropathy. 2011; Ottawa, Ontario: Canadian Association of Radiologists. Available at https://www.car.ca/uploads/standards%20guidelines/20110617_en_prevention_cin.pdf

4.Laskey WK, Jenkins C, Selzer F, et al; NHLBI Dynamic Registry Investigators. Volume-to-creatinine clearance ratio: a pharmacokinetically based risk factor for prediction of early creatinine increase after percutaneous coronary intervention. J Am Coll Cardiol. 2007 Aug 14;50(7):584-590. 

5.University of Kentucky Chandler Medical Center. Guidelines for Contrast-Induced Nephropathy (CIN) Prevention in Adults. 2009. Available at https://www.hosp.uky.edu/pharmacy/formulary/criteria/ContrastNephropathyGuidelines.pdf