Protecting Cath Lab Patients from Contrast-Induced Nephropathy: A Review

One of the leading causes of renal failure in patients following diagnostic and interventional cardiac procedures is contrast-induced nephropathy (CIN). As imaging modalities continue to evolve, more patients (especially the elderly) will be treated and diagnosed with contrast-enhanced imagery. The CIN rate varies from 5% to 38%, depending on patient risk factors. For example, this means a lab performing 1000-plus cases a year could have almost 400 patients at risk for CIN. CIN is defined as a 25% or greater increase in serum creatinine, or a decrease in calculated creatinine clearance in the appropriate clinical setting. Exposure to intravenous or intra-arterial contrast can cause a rise in creatinine within the first 24 hours; continuing over a period of 48 hours, serum creatinine (SCr) will typically peak within 48-72 hours after contrast exposure, and in the absence of other explanations for acute renal failure such as nephrotoxins, hypotension, and urinary obstruction. As cardiovascular professionals working in the lab, we rarely see the latent effects of the cath lab procedure on our patients once their intervention is complete and they leave the hospital. Cath lab staff are unlikely to ever see the renal damage that can occur in the 48 to 72 hours following these cases. The only effects we may encounter with a case would be anaphylaxis, cardiac arrest or cardiac arrhythmia. So, what can be done to preserve the renal function of patients? CIN occurs with much greater frequency and is more insidious than other explanations for acute renal failure such as nephrotoxins, hypotension, and urinary obstruction, with effects that may not be visible. Long-term studies show that CIN is associated with an increase of in-hospital mortality, from up to 30 days and as far out as one year. The concept is that contrast media agents stimulate vasoconstriction in the vascular bed of the renal bodies and decrease the ability of the organs to vasodilate. Some agents appear to cause ischemia by causing an increase of calcium ions in the renal vascular smooth muscle cells. The combination of the an increase in calcium ions and renovascular bed ischemia lowers the glomerular filtration rate (GFR). In addition, contrast media irritates erythrocytes (red blood cells), which increases blood viscosity and causes cellular depletion of oxygen. Since CIN can take several days to develop, patients might be discharged before any symptoms are evident. As a result, post-care educational processes should cover the signs and symptoms of renal dysfunction and how to contact the physician. The assigned nurse and the physician should emphasize oral hydration, provided the patient’s overall health condition does not contraindicate increased fluid intake (i.e. congestive heart failure or pulmonary hypertension). Instructions should include the need to watch for weight gain (>1 kg or 2 lbs per day), edema or if other signs appear the first days following their procedure. By the time renal failure symptoms are visible, renal function is decreased by as much as 75%. However, renal function in some patients does begin to recover and return to normal over time (unless additional contrast studies are needed). Therefore, the cath lab team needs to be aware of the potential of CIN and be prepared to reduce its occurrence. Factors Increasing Risk of CIN Improvement of patient outcomes requires the recognition of those patients which are high risk and have the potential for contrast-induced acute renal failure. There are many factors that may predispose a patient’s incidence of CIN. Pre-existing decreased renal function puts them in the high-risk category. The lower the renal function, the higher the risk of failure. We should, as well, be aware of any other co-morbidities, particularly diabetes and impaired cardiac function. Patients with diabetes and pre-existing renal insufficiency have the greatest risk of CIN. When patients in this group develop CIN, they more than often develop oliguria (diminished frequency of urination) as well. Screening for any contrast-related problems would be the simplest approach. One of the easiest ways to be on top of this potentially fatal complication is to check the blood urea nitrogen and creatinine levels prior to procedure to assure that they are within normal limits. If the patient is at the threshold or below, notify the physician prior to placing patient on the table. The physician can then determine whether to return the patient to his room for hydration and come back later in the day, do the procedure and schedule dialysis after the case, or scrub the case if the patient is not emergent. Calculating the patient’s glomerular filtration rate (GFR) or creatinine clearance is another way to recognize any potential issues. The normal ranges of GFR, adjusted for body surface area, are: • Males: 70 ± 14 mL/min/m2 • Females: 60 ± 10 mL/min/m2 Estimation Using Creatinine Clearance In clinical practice, creatinine clearance is used to measure GFR. Creatinine is an endogenous molecule, synthesized in the body, which is freely filtered by the glomeruli (but also secreted by the renal tubules in very small amounts). Creatinine clearance is therefore a close approximation of the GFR. Many labs use serum creatinine instead. All patients coming into the lab receiving contrast should have their creatinine clearance calculated; it takes just a minute to do so. The formula requires the age, weight and creatinine level. This is a simple test and a commonly used indicator of renal function. A rise in blood creatinine levels is observed only with marked damage to functioning nephrons. Therefore, this test is not suitable for detecting early stage kidney disease. However, the approximation of the GFR calculation is best measured by the evaluation and visualization of the frequency and duration of urination. The GFR is typically recorded in units of volume per time, e.g. milliliters per minute (ml/min). Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour he excretes 75 mg of creatinine in urine. The GFR is calculated as M/P (where M is the mass of creatinine excreted per unit time and P is the plasma concentration of creatinine). Modification of Diet in Renal Disease (MDRD) Formula The most commonly used formula is the “4-variable MDRD” which estimates GFR using four variables: serum creatinine, age, race and gender. The original MDRD used six variables, with the additional variables being the blood urea nitrogen and albumin levels. The equations have been validated in patients with chronic kidney disease; however, both versions underestimate the GFR in healthy patients with GFRs over 60 mL/min. The equations have not been validated in acute renal failure. Cockroft Gault Formula This is another formula that some facilities may use. The Cockcroft-Gault equation aims to predict creatinine clearance from knowledge of serum creatinine, age and weight. A presentation at the 2008 Chronic Total Occlusion (CTO) Summit in New York, NY was given by Dr. Roxana Mehran in reference to CIN prevention, causes and treatments. A “scheme to define CIN risk” was introduced along with a scoring system that incorporated a series of risk factors predicting the potential for CIN (Figure 1). As professionals working in the lab, it is unrealistic to expect that these formulas and schemes be used prior to each case. The formulas are very accurate and beneficial, but generally too complex and lengthy to be used pre-intervention, when all factors cannot necessarily be accounted for in the fast-paced environment of the cath lab. In the “real world” of cardiac and peripheral intervention, there needs to be a simple, accurate way to determine patient risk and how to properly protect them from CIN. At our facility, we include eGFR (estimate) as a standard in all drawn renal panels. It eliminates the need to figure out complex equations. In addition, most contrast media representatives should be able to provide simple slide rules to estimate CrCl using the patient’s age, weight, sex and SrCr. By implementing a screening process, we can achieve better outcomes for our patients and better manage the problem of CIN. Prevention focuses on limiting risk factors. Hydration is imperative to preventing CIN. The Cardiovascular Research Foundation/Columbia University Medical Center conducted a trial comparing the efficacy of 0.9% saline and 0.45% sodium chloride in 1383 patients to help determine an optimal hydration regimen. The study showed that 0.45% sodium chloride had an increased incidence of CIN by 2%, whereas 0.9% saline had only an increased incidence of less than 1%. In addition to hydration, N-acetylcysteine (NAC) seems to have an effect in the prevention of CIN. A prospective, randomized study at Columbia University Medical Center took 83 high-risk patients with a CrCl

1. Solomon R. The role of osmolality in the incidence of contrast induced nephropathy: a systematic review of angiographic contrast media in high-risk patients. Kidney Intl 2005; 68:2256-2263. 2. Rudnick MR, Kesselheim A, Goldfarb S. Contrast-induced nephropathy: how it develops, how to prevent it. Cleve Clin J Med 2006; 73:75-80, 83-7. 3. Stone GW, McCullough PA, Tumlin JA, et al. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: A randomized controlled trial. JAMA 2003; 290:2284–2291. 4. Tadros GM, Malik JA, Manske CL. Iso-osmolar radio contrast iodixanol in patients with chronic kidney disease. J Invasive Cardiol 2005;17:211–215.9 Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;105: 2259–2264. 5. Aspelin P, Aubry P, Fransson S-G, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003; 348: 491–499. 6. Solomon R, Werner C, Mann D, et al. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med 1994; 331:1416-1420. 7. 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: 1237-1242. 8. McCullough PA, Wolyn R, Rocher LL, et al. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997; 103:368-375. 9. Caro JJ, Trindade E, McGregor M. The cost-effectiveness of replacing high-osmolality with low-osmolality contrast media. Am J Roentgenol 1992;159:869-874. 10. Kohtz C and Thompson M. Preventing contrast medium-induced nephropathy. Am J Nurs 2007 Sep;107(9):40-49.