# Presentation: 049870

## Spotlight Case April 2005

**Compare and Contrast**

## Source and Credits

- This presentation is based on the April 2005 Spotlight Case in Emergency Medicine
- See the full article at _[http://webmm.ahrq.gov](http://webmm.ahrq.gov/)__  _
- CME credit is available through the Web site
- Commentary by: Kerry Cho, MD; Glenn Chertow, MD, MPH, UCSF School of Medicine
- Editor, AHRQ WebM&M: Robert Wachter, MD
- Spotlight Editor: Tracy Minichiello, MD
- Managing Editor: Erin Hartman, MS

## Objectives

*	**At the conclusion of this educational activity, participants should be able to:*
- Define contrast nephropathy (CN)
- List risk factors for CN
- Implement pharmacologic strategies for CN prophylaxis
- Follow algorithm for CN risk reduction and prevention

## Case: Compare and Contrast

*	**A 76-year-old woman came to the emergency department complaining of vomiting, dehydration, and abdominal pain. An abdominal x-ray revealed a pattern consistent with a partial small bowel obstruction. On admission, BUN was 32 mg/dL and creatinine was 1.4 mg/dL. She underwent a contrast-enhanced abdominal CT to look for a lead point in the bowel obstruction. *

## Contrast Nephropathy (CN)

- Definition: an increase of ≥ 0.5 mg/dL or ≥ 25% in serum creatinine concentration within 48 hours following contrast exposure
- Calculate baseline renal function
- _[GFR MDRD Calculator for Adults](http://www.nkdep.nih.gov/healthprofessionals/tools/gfr_adults.htm)__: GFR (ml/min/1.73 m2) = 186 x (PCR)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American) _
- _[Cockcroft-Gault formula](http://www.mssm.edu/medicine/general-medicine/ebm/CPR/TOOLS/CrClearance.html)__: Creatinine Clearance (ml/min) = [(140 - age) * weight (in kg)] / [72 * serum creatinine (mg/dL)] _
- Multiply by 0.85 if female

*Levey AS, et al. Ann Intern Med. 1999;130:461-70.*
*Levey AS, et al. Ann Intern Med. 2003;139:137-47. *

**Notes:**
1. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-70.
2. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137-47.

## Risk Factors for CN

- Pre-existing chronic kidney disease
- GFR/creatinine clearance < 60 mL/min/1.73 m2 considered a risk factor for CN
- Diabetes mellitus with proteinuria
- Multiple myeloma
- Large volume of radiocontrast
- Congestive heart failure
- Decreased renal perfusion

*Murphy SW, et al. J Am Soc Nephrol. 2000;11:177-82.*
*Gami AS, et al. Mayo Clin Proc. 2004;79:211-9.  *

**Notes:**
3. Murphy SW, Barrett BJ, Parfrey PS. Contrast nephropathy. J Am Soc Nephrol. 2000;11:177-82.
4. Gami AS, Garovic VD. Contrast nephropathy after coronary angiography. Mayo Clin Proc. 2004;79:211-9.

## Additional Risk Factors for CN

- Older age (with normal kidney function)
- Concomitant use of selected drugs
- amphotericin B, cyclosporin A, tacrolimus, diuretics, and non-steroidal anti-inflammatory drugs
- Proteinuria of any cause
- Peri-procedural complications and hypotension

## Risk Factors for Contrast Nephropathy

*Rich MW, Crecelius CA. Arch Intern Med. 1990;150:1237-42.*
* *

**Notes:**
5. Rich MW, Crecelius CA. Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. Arch Intern Med. 1990;150:1237-42.

In one study of older patients receiving coronary angiography, the incidence of CN was only 1.2% in patients without risk factors, but increased to 11.2% with one risk factor and more than 20% with two risk factors.5

## Case (cont.): Compare and Contrast

*	**By hospital day number 3, the patient’s urine output was minimal, and the BUN and creatinine had risen to 70 mg/dL and 3.5 mg/dL, respectively. Her small bowel obstruction continued to improve and no surgical intervention was necessary.*

## Prevention of Contrast Nephropathy

- Avoid contrast
- Use ultrasound, MRI
- Use small amounts of contrast
- Select less toxic radiocontrast agents
- Iso-osmolar and low osmolar contrast associated with lower risk of CN
- Avoid concomitant use of nephrotoxic agents

*Barrett BJ, Carlisle EJ. Radiology. 1993;188:171-8.*
*Aspelin P, et al. N Engl J Med. 2003;348:491-9. *

**Notes:**
7. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology. 1993;188:171-8.
8. Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ, for the NEPHRIC Study Investigators. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003;348:491-9.

A meta-analysis comparing low-osmolar contrast material with traditional agents found a reduced risk of CN in patients with chronic kidney disease.7 
 A recent randomized clinical trial found that iodixanol, an iso-osmolar agent, was less nephrotoxic than low-osmolar iohexol in patients with diabetes and an elevated serum creatinine concentration undergoing coronary or aortofemoral angiography.8

## Pharmacologic Prevention of Nephropathy

- Effective strategies
- N-acetylcysteine
- Normal saline
- Sodium bicarbonate
- Methylxanthines

- Ineffective strategies
- Calcium channel blockers
- Mannitol
- Furosemide
- Atrial natriuretic peptide
- Endothelin antagonists
- Dopamine
- Fenoldopam
- Hemodialysis

*Ide JM. Invest Radiol. 2004;39:155-70.*

**Notes:**
9. Ide JM, Lancelot E, Pines E, Corot C. Prophylaxis of iodinated contrast media-induced nephropathy: a pharmacological point of view. Invest Radiol. 2004;39:155-70.

## N-acetylcysteine for Prevention of CN

- Original report found RR of 0.1 of CN with administration of 600 mg BID starting the day prior X 4 doses when compared to placebo
- Recent meta-analyses published
- Majority show a benefit

*Tepel M. et al. N Engl J Med. 2000;343:180-4.*
*Nallamothu BK, et al. Am J Med. 2004;117:938-47.*

**Notes:**
10. 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. 2000;343:180-4.
11. Nallamothu BK, Shojania KG, Saint S, et al. Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis. Am J Med. 2004;117:938-47.

## Sodium Bicarbonate for Prevention of CN

- Randomized trial of sodium bicarbonate vs normal saline
- Baseline creatinine > 1.1mg/dl
- Infusion rates were 3 mL/kg/hour for 1 hour before and 1 mL/kg/hour for 6 hours after radiocontrast exposure
- N-acetylcysteine not administered

*Merten GJ, et al. JAMA. 2004;291:2328-34. *

**Notes:**
12. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004;291:2328-34.

One hundred and nineteen subjects 
These patients did not receive N-acetylcysteine.  
 CN defined as a 25% increase in serum creatinine within two days of exposure 
Low rates of CN were subsequently confirmed in an open label study of 191 subjects given a simplified isotonic sodium bicarbonate infusion with radiocontrast exposure.  

## CN defined as a  25% increase in serum creatinine within 2 days of exposure
Incidence of CN: 1.7% in the bicarbonate group vs. 13.6% in the saline group
Low rates of CN subsequently confirmed in open-label study of 191 subjects given a simplified isotonic sodium bicarbonate infusion with radiocontrast exposure

- Incidence of CN: 1.7% in the bicarbonate group vs. 13.6% in the saline group
- Low rates of CN subsequently confirmed in open-label study of 191 subjects given a simplified isotonic sodium bicarbonate infusion with radiocontrast exposure

*Merten GJ, et al. JAMA. 2004;291:2328-34. *

**Sodium Bicarbonate for Prevention****of CN (cont.)**

**Notes:**
12. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004;291:2328-34.

## Methylxanthine for Prevention of Nephropathy

- Recent meta-analysis of theophylline and aminophylline concluded these agents reduce rise in serum creatinine following contrast exposure
- Did not report the fraction of patients experiencing > 0.05 increase in serum creatinine, so clinical significance unclear

*Ix JH, et al. Nephrol Dial Transplant. 2004;19:2747-53. *

**Notes:**
15. Ix JH, McCulloch CE, Chertow GM. Theophylline for the prevention of radiocontrast nephropathy: a meta-analysis. Nephrol Dial Transplant. 2004;19:2747-53.

## Case (cont.): Compare and Contrast

*	**Due to continued oliguria and persistent uremia hemodialysis was started on hospital day number 5. *

## Outcome of Contrast Nephropathy

- Mortality rates higher
- Odds of death increased by a factor of 5.5 in patients with CN
- Length of stay (LOS) increased
- LOS 6 days vs 1 in patients without CN
- Need for dialysis is rare
-  <1%

*McCullough PA, et al. Am J Med. 1997;103:368-75.*
*Levy EM, et al. JAMA. 1996;275:1489-94.*
*Aronow HD, et al. Am Heart J. 2001;142:799-805.   *

**Notes:**
6. 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;103:368-75.
16. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort analysis. JAMA. 1996;275:1489-94.
17. Aronow HD, Peyser PA, Eagle KA, et al. Predictors of length of stay after coronary stenting. Am Heart J. 2001;142:799-805.

## Avoiding the Complication

- Low-risk patients have a low incidence of nephropathy, 1% or less
- Do not need any prophylaxis
- Among high risk patients, chronic kidney disease and other risk factors are relative contraindications to radiocontrast exposure
- Should receive prophylaxis

*Maeder et al. J Am Coll Cardiol. 2004;44:1763-71. Waybill et al. J Vasc Interv Radiol. 2001;12:3-9.  *

## Balancing Risk with Benefit

- Renal insufficiency and other risk factors are not an absolute contraindication to radiocontrast studies
- In one study, elderly patients with chronic kidney disease were half as likely to undergo coronary angiography **despite** equivalently appropriate clinical indications
- Therefore, delaying appropriate testing to administer CN prophylaxis or avoidance contrast studies entirely can be a dangerous strategy

*Chertow GM, et al. J Am Soc Nephrol. 2004;15:2462-8.*

**Notes:**
20. Chertow GM, Normand SL, McNeil BJ. "Renalism": inappropriately low rates of coronary angiography in elderly individuals with renal insufficiency. J Am Soc Nephrol. 2004;15:2462-8.

## Take-Home Points

- Estimate kidney function and risk factors prior to contrast administration
- In at-risk patients, consider the urgency of the clinical situation, and the possibility of using non-contrast imaging or delaying imaging to administer prophylactic modalities
- Do not delay urgent diagnostic studies, as the delay-associated hazard frequently outweighs the risk of CN

## Take-Home Points

- If contrast is administered, avoid nephrotoxic medications before and after radiocontrast exposure
- The dose of contrast should be minimized, and iso-osmolar contrast material is preferable
- Consider nephrology consultation to assist in risk assessment, patient education, and supportive care