Continuing Education Activity
Iodine contrast medium is essential in invasive and interventional cardiac procedures. Because of an increasing number of coronary angiography and coronary interventional procedures, the increasing use of contrast media, and the increasing number of invasive cardiac procedures being performed in high-risk patients with chronic kidney disease, diabetes mellitus, hypertension, and kidney failure due to contrast-induced nephropathy remains a growing concern. A sudden change in kidney function is a common complication of coronary angiography, and percutaneous coronary intervention, primarily because of contrast-induced acute kidney injury or contrast-induced nephropathy. This activity reviews the pathophysiology of contrast-induced nephropathy and highlights the role of the interprofessional team in its management and prevention.
- Describe the risk factors for contrast-induced nephropathy.
- Review the pathophysiology of contrast-induced nephropathy.
- Summarize the treatment and prevention of contrast-induced nephropathy.
- Outline the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by contrast-induced nephropathy.
Iodine contrast medium is essential in invasive and interventional cardiac procedures. Because of an increasing number of coronary angiography and coronary interventional procedures, the increasing use of contrast media, and the increasing number of invasive cardiac procedures being performed in high-risk patients with chronic kidney disease, diabetes mellitus, hypertension, and kidney failure due to contrast-induced nephropathy remains a growing concern. A sudden change in kidney function is a common complication of coronary angiography, and percutaneous coronary intervention, primarily because of contrast-induced acute kidney injury or contrast-induced nephropathy.
The most common cause of contrast-induced nephropathy is pre-existing chronic kidney disease. About 8% of patient with estimated glomerular filtration rate (eGFR) between 45 ml/min/1.73m2 to 60 ml/min/1.73m2, 13% of the patients with eGFR between 30 ml/min/1.73m2 to 45 ml/min/1.73m2, and 27% of patients with glomerular filtration rate (GFR) less than 30 ml/min/1.73m2 develop contrast-induced nephropathy following contrast exposure. 
Other clinical factors include advanced age, diabetes, peripheral heart failure, females, peripheral vascular disease, hypertension and a left ventricular ejection fraction (LVEF) of less than 40%. Precipitating factors include acute coronary syndrome, hypotension, volume depletion, concomitant nephrotoxic medications, and anemia. There are several risk predictor models available to predict contrast-induced nephropathy risk before the procedure and use of preventive measures. Gurm and colleagues used a cohort of over 68,000 percutaneous coronary intervention procedures to develop an online calculator risk predictor (http://bmc2.org/calculators/cin).
Similarly, the Roxana Mehran score predictor applies the following ten variables:
- Age (4 points if older than 75 years old)
- Anemia (3 points)
- Use of an intra-aortic balloon pump (5 points)
- eGFR 60 to 40 (2 points)
- eGFR 40 to 20 (4 points)
- eGFR less than 20 (6 points)
- Hypotension (5 points, if systolic BP less than 80 mmHg for at least one hour requiring inotropic support)
- Contrast media volume (1 point per 100 ml)
- Congestive heart failure (5 points)
- Diabetes (3 points).
A risk score of less than 6 carries a risk of 7.5% to score more than 16 carries up to 57% risk.
The prevalence of diabetes and chronic kidney disease is rising. Both of these are risk factors for acute kidney injury after cardiac catheterization and percutaneous coronary interventions. Based on current definitions the incidence of contrast-induced nephropathy ranges from 2% to 30%. Most cases are completely reversible within two to four weeks. The need for renal replacement therapy is rare at a rate of 1% to 4%, and of these, less than 50% require long-term renal replacement therapy. The incidence of contrast-induced nephropathy is calculated to be more than 2% in the general population. However, in high-risk groups with risk factors for kidney disease, the incidence is as high as more than 20% to 30%. It is reported that there is a lower risk of contrast-induced nephropathy when low osmolar contrast media is used.
The pathophysiology of contrast-induced nephropathy remains unclear. The proposed theory is a combination of vasoconstriction, ischemia, hypoxia, and direct toxic effect on renal tubular cells. The hemodynamic alterations and medications can exacerbate the possibility of contrast-induced nephropathy. The risk of contrast-induced kidney injury is much higher with the arterial administration of contrast compared with venous administration of contrast. Metformin can cause lactic acidosis in the setting of kidney dysfunction and acute kidney injury. The FDA recommends holding metformin on the day of contrast exposure and 48 hours after the procedure. Another cause is catheter-induced aeroembolism to the renal microvasculature. Laboratory abnormalities may include eosinophilia and eosinophilia in an acute kidney injury as a result of cholesterol atheroembolism.
When kidney biopsies are done, there is visible evidence of direct damage to the renal tubular epithelial cells by the contrast dye. One may note the presence of interstitial inflammation, cell vacuolization, and patch necrosis. This damage to the cells is usually evident within the first 7-10 days of the injury.
History and Physical
Contrast-induced nephropathy was first reported by Bartel et al. in the 1950s and was related to a fatal acute renal injury that happened following intravenous pyelography in a patient with myeloma kidney. A transient rise in creatine occurs in 15% of patients undergoing invasive procedures. Even mild contrast-induced nephropathy is associated with longer hospital stays, increased cost, and higher short-term and long-term mortality. The reported incidence varies between 7% and 11% depending on the definition applied, study population, and setting. An average additional cost of more than $10,000 is associated with a contrast-induced nephropathy-related hospital stay. Contrast-induced acute kidney injury is diagnosed by following up on creatinine levels two to three days after contrast exposure.
Contrast-induced nephropathy is defined as a rise in serum creatinine of at least 0.5 mg/dL or 25% increase from baseline within 48 to 72 hours after contrast exposure. The Kidney Disease Improving Global Outcome (KDIGO) definition is different, with stage I being a rapid rise of creatinine to greater than 0.3 mg/dL within 48 hours or the relative rise of 50% or more from baseline in 7 days or less or a reduction in urine output to less than 0.5 ml/kg/hr for 6 to 12 hours. This severity is further staged based on creatinine levels, urine output or need for renal replacement therapy. 
Treatment / Management
The most common strategy to reduce the risk of contrast-induced neuropathy must be considered before the contrast exposure. Periprocedural hydration in chronic kidney disease patients by initiating intravenous (IV) fluid with 0.9% normal saline infusion at a rate of 1 ml/kg/hr for six to 12 hours before the procedure and continuing after the procedure. Some literature supports a sliding scale IV hydration protocol based on left ventricular end-diastolic pressure.
In a clinical trial, there was no consistent benefit to justify the routine administration of sodium bicarbonate in patients undergoing cardiac catheterization. Similarly, the Acetylcysteine for Contrast-Induced Nephropathy trial found no difference between acetylcysteine and placebo in the prevention of contrast-induced neuropathy or need for dialysis. It is reasonable to pretreat patients with high-intensity statin before contrast use. Fenoldopam, a dopamine receptor agonist, did not have any benefit in clinical trials. Ascorbic acid 1 gm to 3 gm for one to 3 days periprocedural has been shown to reduce contrast-induced neuropathy by 33%. RenalGuard System has shown promise in high-risk patients. The benefit of hemofiltration has been demonstrated in an isolated trial. Intraprocedure, one can use smaller guide catheter, minimize contrast use, avoid ventriculogram, biplane coronary angiography, low osmolar, or iso-osmolar nonionic contrast agent, and maximum allowable contrast dose to be three times the estimated GFR.
- Acute renal failure
- Embolic renal disease
- Interstitial nephritis
- Acute tubular necrosis
- Renal artery stenosis
Toxicity and Side Effect Management
Hypersensitivity or allergic reactions can be treated by the use of steroids, epinephrine, and anti-histamines.
Several scoring systems have been developed to predict contrast-induced kidney injury and the risk factors include the following:
- Use of an intra-aortic balloon pump
- Congestive heart failure (CHF)
- Elevated creatinine (More than 1.5)
- Age greater than 75
- Use of contrast volume more than 100 ml
Overall, the prognosis depends on patients' co-morbidities including but not limited to baseline renal function. Depending upon the scoring system, following contrast administration, there can be a probability of CIN. Generally, it is reversible and biopsy is rarely needed for the diagnosis.
- Acute renal failure
- Acute on chronic renal failure
- Hypersensitivity reactions
- Fluid overload
- Pulmonary edema
- Contrast-induced thyroid dysfunction
Deterrence and Patient Education
CIN is usually reversible and can present with a mild reduction in GFR that tends to improve within three to seven days. Most of the patients return to, or close to, their baseline estimated GFR. People with advanced renal failure may temporarily need dialysis following contrast administration.
Pearls and Other Issues
Approximately 42% of deaths among patients with end-stage renal disease (ESRD) are due to a cardiovascular event. Routine dialysis is not the recommendation in a patient with end-stage renal disease undergoing cardiac catheterization. They can be maintained on their routine dialysis schedule.
It is important to recognize that precaution is needed in a patient with transplanted kidney undergoing cardiac catheterization. Instrumentation of the vessel that supplies the transplanted kidney should be avoided. Additionally, contrast should be used judiciously even with normal GFR, avoid indwelling arterial or venous catheters and use of vascular closure device due to the risk of infection.
Assessment of acute kidney injury with serum creatinine has poor sensitivity and specificity. Several new markers have been identified with most of the current interest focused on cystatin C, neutrophil gelatinase-associated lipocalin, interleukin 18, and kidney injury molecule 1.
Enhancing Healthcare Team Outcomes
Because contrast-induced renal injury leads to high morbidity, prolonged admission and increased health care costs, the goal is today is focussed on prevention. Besides physicians, both the nurse and pharmacist need to be aware of the patient's medical history and concomitant use of other medications. A detailed history of risk factors like diabetes, heart failure and hypertension are critical. Any patient prescribed an intervention procedure that uses contrast dye must be fully assessed for a history of diabetes and renal function. These individuals may be better served with another imaging test that does not require the use of contrast. If there is no choice, then the patient must be educated about the possibility of kidney injury and the need for dialysis. The pharmacist should ensure that all nephrotoxic drugs are discontinued prior to the test. The nurse should make sure that the patient is well hydrated both before and after the test. The drug metformin should be withheld for 48 hours and restarted if the renal function is normal. Only through proper communication and monitoring can the frequency of contrast-induced renal injury be lowered. (Level V)
Contrast-induced kidney injury is in most cases not a permanent injury and most patients will see a recovery of renal function within 10-14 days. However, in patients with underlying renal disease, diabetes or hypertension, about 20-30% of patients will have residual impairment of renal function. Dialysis may be required in less than 1-3% of non-diabetic patients, but in diabetics, dialysis may be required in anywhere from 10-15% of cases. Of those who do required dialysis, at least 20% may end up on permanent dialysis. The presence of persistent kidney damage after use of contrast highlights the importance of hydration and avoidance of contrast when other imaging modalities are available. (Level V)