Contrast-Induced Nephropathy

Contrast-Induced Acute Kidney Injury

"CIN has an adverse effect on prognosis and adds to healthcare costs. This subject is becoming increasingly important to radiologists, cardiologists, and nephrologists."
Peter McCullough (Consensus Panel)1

What is CIN?

Contrast-Induced Nephropathy (CIN) is a form of Acute Renal Failure that is caused by exposure to contrast media during image-guided cardiology and radiology procedures. The lack of effective treatment to prevent CIN remains problematic for patients with renal-insufficiency.

Millions of cardiovascular and peripheral diagnostic and interventional procedures are performed worldwide each year. These less invasive, image-guided medical procedures require the use of an iodine-based radio-contrast media, or dye, to facilitate the capture and display of x-ray images. These contrast agents are known to be toxic to the kidney, whose main function is to filter and remove wastes and fluids from the body. Patients who undergo this type of procedure and who present themselves with a certain level of pre-existing impaired renal (kidney) function are especially susceptible to the toxic effects of these contrast agents and to developing CIN.

In patients at risk, the concentration of contrast agents in the collecting duct may be increased. Along with this continuous concentration process, tubular fluid containing contrast agents will become increasingly viscous and can lead to tubular obstruction. This increases tubular pressure and intrarenal tissue pressure. As a result, renal perfusion pressure for the renal medulla (17mmHg) may no longer be high enough to assure sufficient perfusion to critical kidney areas; thus aggravating hypoxic injury."2

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What are the potential consequences?

CIN is associated with increased:3

  • Major adverse in-hospital cardiac events
  • In-hospital mortality rates
  • Long-term mortality
  • Risk of acceleration toward end-stage renal disease (dialysis)
  • Longer and more frequent hospital stays

According to Marenzi, et al,4, hospitalized patients who received contrast media and who acquired CIN had significantly higher mortality rate (31% vs. .6%) than patients who did not acquire CIN.

These consequences usually lead to higher health care costs.

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What factors may affect a patient's risk of acquiring CIN?

There are many factors that may increase a patient's risk of acquiring CIN. According to Mehran, et al.5, the incidence of CIN increases with these patient-related characteristics:

  • Renal Insufficiency
  • Hypotension
  • Congestive Heart Failure
  • Hypotension
  • Age > 75 years
  • Anemia
  • Diabetes Mellitus

The risk of CIN is directly proportional to the severity of pre-existing renal
insufficiency.6

Patients with renal insufficiency are easily identified with a routine blood analysis that looks at the level of a biological marker called serum creatinine and the consequent calculation of an estimated Glomerular Filtration Rate (eGFR). An eGFR of <60mL/min/1.73m^2 is recognized as the threshold for clinical importance.7

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What is eGFR?

According to the National Kidney Foundation, eGFR is the best estimate of kidney function. Patients with an eGFR of 60 or below are generally considered at risk for acquiring CIN. The chart below describes the stages of kidney disease as it relates to eGFR.

Stage Description Glomerular Filtration Rate (GFR)
At increased risk Risk factors for kidney disease (e.g., diabetes, high blood pressure, family history, older age, ethnic group) More than 90
1 Kidney damage (protein in the urine) and normal GFR More than 90
2 Kidney damage and mild decrease in GFR 60 to 89
3 Moderate decrease in GFR 30 to 59
4 Severe decrease in GFR 15 to 29
5 Kidney failure (dialysis or kidney transplant needed) Less than 15

Reprinted with permission from National Kidney Foundation.  KDOQI clinical Practice Guidelines for Chronic Kidney Disease:  Evaluation, Classification and Stratification.  Am J Kidney Dis 39:S1-S000, 2002 (suppl 1)

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How is CIN determined?

In clinical practice, CIN is usually defined as a relative rise of 25% or an absolute rise of 0.5mg/dL over a baseline in serum creatinine within four days of a procedure where contrast is administered.8

CIN rates vary widely depending on the patient population and baseline risk factors. Studies have shown rates of up to 53% depending on the types of patients studied. CIN rates also depend on the criteria by which it is defined.9

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Are there any effective prevention methods?

"No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing the risk of CIN."
Stacul (Consensus Panel)10

Although many feel that CIN can be prevented, most studies of measures to prevent CIN have either been neutral, found deleterious effects, or have reported conflicting results.11 Specifically, prevention strategies involving calcium-channel blockers, endothelin receptor antagonists, theophylline, prostaglandins, diuretics, anti-oxidants, or other reno-protective drugs have been shown to have no benefit or to have little consistent effect.12

Since higher contrast volumes are associated with higher rates of CIN13 (Davidson, Consensus Panel), many physicians seek to reduce the toxicity of contrast by reducing the volume given to at-risk patients in a procedure. A physician may endeavor to limit the amount of contrast used in a single procedure.

For more complex procedures, a physician may stage procedures, or perform 2-3 procedures over a period of days, allowing for a reduction in the amount of contrast put into the vascular system at one time. Finally, a physician may decide that the risk of complications related to the use of contrast outweighs the benefit of a diagnosis or intervention. These methods may present limitations for patients requiring imaging procedures to advance their care.

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RenalGuard is CE-marked for the intended use of temporary (up to 14 days) replacement of urine output by infusion of a matched volume of sterile replacement solution to maintain a patient’s intravascular fluid volume. The RenalGuard System is not intended for infusion of blood, blood components, medications, or nutritional fluids. All treatments administered via The RenalGuard System must be prescribed by a physician. RenalGuard Solutions, Inc. reserves the right to modify the specifications and features described herein, or discontinue manufacture of the product described at any time without prior notice or obligation.

Caution - Investigational Device, Limited By United States Law to Investigational Use.

1 McCullough et al, Contrast-Induced Nephropathy: Clinical Insights and Practical Guidance
A Report from the CIN Consensus Working Panel, Supplement to the American Journal of Cardiology, Vol. 98 (6A), September 18, 2006

2 Bartorelli, Antonio L., Marenzi, Giancarlo; Contrast-Induced Nephropathy: In Interventional Cardiovascular Medicine, 2005; pp. 3-11

3 Merten et al., Prevention of Contrast-Induced Nephropathy With Sodium Bicarbonate - A Randomized Controlled Trial; JAMA, May 19, 2004; 291; 2328-2334

4 Marenzi, G, Lauri, G, et al. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. JACC 2004;44:780-5

5 Mehran et al., A Simple Risk Score for Prediction of Contrast-Induced Nephropathy After Percutaneous Coronary Intervention; JACC 2004; 44; 1393-9

6 Rudnick et al., Contrast-induced nephropathy: How it develops, how to prevent it; Cleveland Clinic Journal of Medicine January 2006; 73; 75-87

7 See note 1

8 Tepal et al., Contrast-Induced Nephropathy: A Clinical and Evidence-Based Approach; Circulation, 2006;133;1799-1806

9 Stone et al., Fenoldopam Mesylate for the Prevention of Contrast-Induced Nephropathy - A Randomized Controlled Trial; JAMA; 2003; 290; 2284 - 2291

10 See note 1

11 See note 9

12 Marenzi et al., The Prevention of Radiocontrast-Agent-Induced Nephropathy by Hemofiltration; NEJM October 2003 349;14; 1333-1340

13 See note 1