1. Description of the problem

Contrast-induced acute kidney injury (CIAKI) is characterized by an abrupt decline in kidney function following the intravascular administration of iodinated contrast media. CIAKI manifests as an increase in the serum creatinine concentration (SCr) within 2-5 days following the administration of contrast. In severe cases, it may be associated with oliguria or anuria.

Elevation in the SCr and blood urea nitrogen (BUN) typically occur within 2-5 days following contrast administration. In most cases, SCr and BUN peak within 7 days and return toward baseline values by 10 days. Oliguria and anuria can complicate severe cases.

Evaluation of urine electrolytes may demonstrate a low urine sodium concentration (urine Na < 10 mEq/L) and/or a low (<1%) fractional excretion of sodium (urine Na x plasma Cr)/(urine Cr x plasma Na) owing to the vasoconstrictive properties of iodinated contrast.

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Tubular epithelial cell and granular “muddy brown” casts are commonly seen on urine microscopy as CIAKI represents a form of acute tubular necrosis.

Complications of progressive or severe CIAKI are similar to the complications of other etiologies of acute kidney injury and may include hyperkalemia (serum K > 5.5 mEq/L); metabolic acidosis; extracellular volume expansion with pulmonary and peripheral edema; hyperphosphatemia; and, in prolonged cases of AKI, anemia.

2. Emergency Management

Emergency management of CIAKI relates specifically to the acute complications of severe acute kidney injury:

1) Hyperkalemia – medical management of hyperkalemia (i.e., IV calcium, glucose/insulin, inhaled beta agonist, Kayexelate). Renal replacement therapy may be required in severe and/or refractory cases.

2) Volume overload/pulmonary edema – IV diuretics, restriction of sodium intake, provision of renal replacement therapy or isolated ultrafiltration in refractory cases

3) Metabolic acidosis – supplemental sodium bicarbonate administered PO and/or IV. In cases of severe metabolic acidosis, provision of renal replacement therapy.

4) Pericarditis – provision of renal replacement therapy

3. Diagnosis

Diagnostic criteria and tests

CIAKI is commonly defined as an increase in SCr >= 0.5 mg/dL and/or >= 25% within 2-5 days following contrast administration.

Tests to aid in diagnosis

– Spot urine electrolytes (i.e., Na, Cl) and urine creatinine ▸ (low urine Na and fractional excretion of Na)

– Urine dipstick and microscopy ▸ concentrated urine and muddy brown granular casts

– Renal ultrasound (or alternative imaging of the kidney) ▸ helps rule out obstructive causes of acute kidney injury

– Assessment of post-void residual volume ▸ helps rule out obstructive causes of acute kidney injury

Diagnosis is based on characteristic rise in SCr within 2-5 days of intravascular administration of iodinated contrast material in the absence of other known nephrotoxic insults. In the setting of other known insults to the kidney, intravascular iodinated contrast may contribute to and/or exacerbate renal injury.

Primary differential diagnosis of CIAKI

1) Atheroembolic renal disease – atheroembolic disease results from showering of atheromatous debris into the microcirculation of the kidney and other organs. Although the time course of kidney injury in atheroembolic disease is highly variable, it characteristically develops 1-2 weeks following intravascular instrumentation (e.g., coronary angiography, aortography) as compared to the rise in SCr over 2-5 days associated with CIAKI. Atheroembolic disease is often accompanied by extra-renal organ involvement (e.g., CNS, GI, skin). Clinical features of atheroembolic renal disease not present in CIAKI include hypocomplementemia and livedo reticularis.

2) Pre-renal AKI due to decreased absolute or effective circulating volume and reduced renal perfusion. As may occur with CIAKI, pre-renal AKI is characterized by low urine Na and FeNa. Unlike CIAKI, renal tubular epithelial/coarse granular casts on urine microscopy are absent in the setting of pre-renal AKI. Pre-renal AKI responds to intravascular volume administration, whereas established acute tubular necrosis from intravascular contrast administration does not respond to therapeutic intravascular volume expansion.

3) Alternative causes of acute tubular necrosis (ATN) – ischemic (e.g., secondary to hypotension), other nephrotoxic medications including aminoglycosides

Confirmatory tests

Diagnosis of CIAKI is confirmed based on characteristic clinical course following intravascular iodinated contrast administration and the exclusion of alternative etiologies of AKI.

4. Specific Treatment

CIAKI is one of the few preventable forms of acute kidney injury. Therefore, the primary focus of therapy is preventative. The approach to prevention involves the following steps:

1) Identify patients at high risk based on known patient and procedural-related risk factors (Table I). Renal insufficiency, commonly defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, is the principal risk factor. Diabetes mellitus in the absence of underlying kidney disease is not a strong risk factor. However, diabetes mellitus substantially amplifies the risk in the setting of underlying renal insufficiency.

Table I.

Principal risk factors for CIAKI.

2) Consider use of alternative imaging modalities that do not require the administration of iodinated contrast in high-risk patients. When considering the use of magnetic resonance imaging (i.e., MRI, MRA) with gadolinium-based contrast agents as alternative imaging modalities in patients with very advanced chronic kidney disease or end-stage renal disease, the potential for developing nephrogenic systemic fibrosis must be considered.

3) Discontinue potentially nephrotoxic medications (i.e., selective and non-selective nonsteroidal anti-inflammatory agents) prior to contrast administration and withold until confirmation has been made that CIAKI has not developed.

4) Administer intravenous fluids (crystalloid) prior to and following the contrast-enhanced procedure. Use of either isotonic sodium chloride (saline) or isotonic sodium bicarbonate is advised and meets the current standard of care (see below for recommendations on dosing). Data from clinical trials and meta-analyses on the comparative effectiveness of isotonic sodium bicarbonate and isotonic saline are disparate and definitive conclusions on the superiority of isotonic bicarbonate compared to saline cannot be drawn based on currently available data.

5) Administration of oral N-acetylcysteine (NAC) on the day of and the day following the contrast-enhanced procedure (see below for recommendations on dosing). While data supporting the effectiveness of NAC for the prevention of CIAKI are inconclusive, the oral formulation of this agent is generally safe and inexpensive. Therefore, until adequately powered trials conclusively define the role of this antioxidant, use of NAC is generally recommended albeit not in lieu of other preventive measures (i.e., periprocedural intravenous isotonic crystalloid administration).

6) Avoid the use of high-osmolal contrast media. High-osmolal contrast media are associated with an increased risk of CIAKI as compared to low-osmolal and iso-osmolal contrast media. There does not appear to be a consistent benefit of iodixanol, the only iso-osmolal contrast agent available in the United States, as compared to low-osmolal agents; however, there may be an increased risk of CIAKI with specific low-osmolal agents, particularly iohexol and ioxaglate.

7) Minimize volume of contrast administered to the degree possible without compromising the diagnostic yield of the procedure.

8) Discontinue metformin therapy following contrast administration. While metformin is not nephrotoxic and does not increase the patient’s risk for CIAKI, use of this medication in a patient who develops CIAKI increases the risk for life-threatening metabolic acidosis. Once confirmation is made that CIAKI has not developed, metformin therapy can be reinitiated. Accordingly, the effects of holding metformin on serum glucose levels should be monitored closely and consideration given to providing alternative hypoglycemic therapy as appropriate and in consultation with the primary provider.

Data on the discontinuation of ACE inhibitors and angiotensin receptor blockers (ARB) are mixed. There are no sound data supporting the discontinuation of these agents prior to contrast administration, and therefore no recommendation is made to discontinue these agents at the time of contrast administration.

INTERVENTIONS WITH UNPROVEN EFFICACY FOR THE PREVENTION OF CIAKI: aminophylline, theophylline, HMG Co-A reductase inhibitors (statins), prostaglandin analogs, ascorbic acid, calcium channel blockers, hemofiltration. There are currently insufficient data to recommended the use of these interventions to prevent CIAKI.

POTENTIALLY DELETERIOUS INTERVENTIONS : furosemide, mannitol, dopamine, fenoldopam, hemodialysis. Use of these interventions is not recommended.

Drugs and dosages

N-acetylcysteine – consider 1,200 mg po twice daily on day of and day following the contrast-enhanced procedure. Preliminary data suggest that a dose of 1,200 mg is more effective that 600 mg with no substantial difference in the risk for adverse effects.

Isotonic sodium bicarbonate or isotonic saline – for hospitalized patients, administer at a rate of 1 ml/kg per hour for 6-12 hours prior to and 6-12 hours following the procedure. For outpatients and those undergoing urgent/emergent procedures, consider 3 ml/kg/hr for 1 hour prior to contrast administration and 1 to 1.5 ml/kg/hr for at least 4-6 hours following contrast administration.

5. Disease monitoring, follow-up and disposition

Monitoring for the development of CIAKI involves measuring renal function (i.e., SCr) within 2-5 days following the contrast-enhanced procedure among patients at increased risk (i.e., patients with baseline eGFR < 60 ml/min/1.73m2 and/or other known risk factors for CIAKI). For patients who do not demonstrate an increase in SCr within this time frame, no further biochemical monitoring is required.

Patients who demonstrate a post-procedure decrement in kidney function (i.e., increase in SCr) should have kidney function monitored serially, instructed to avoid any other nephrotoxic insults, and followed for the development of clinical and/or serological complications of AKI.

Incorrect diagnosis

An alternative diagnosis of AKI should be suspected when renal injury develops more than 7-10 days following the administration of iodinated contrast. In such instances, careful evaluation for alternative causes of AKI, including atheroembolic disease, should be undertaken.


The pathophysiology of CIAKI is believed to be related to 3 processes:

1) Mismatch of oxygen supply and demand ► medullary ischemia

2) Direct toxicity to renal tubular epithelial cells

3) Generation of reactive oxygen species ► exacerbate tubular cell injury


The epidemiology of CIAKI varies considerably based on three principal factors:

1) Definition of CIAKI – the most commonly used definition of CIAKI is based on an increase in SCr >= 0.5 mg/dL and/or >= 25%. However, more robust increments in SCr of >= 1.0 mg/dL or >= 50% have been used to define this condition, which results in fewer patients meeting the criteria for a diagnosis of CIAKI.

2) Underlying risk – among patients with no underlying risk factors, the incidence of CIAKI is exceedingly low. Among patients at higher risk for CIAKI (e.g., presence of chronic kidney disease), the risk varies by the number and severity of risk factors. Risk increases inversely with level of renal function.

3) Type of procedure – the observed incidence of CIAKI has generally been higher among patients undergoing angiography compared to computed tomography. This may relate to differences in the underlying level of comorbidity in the population of patients undergoing these two types of procedures and/or differential effects of intra-arterial versus intravenous administration of iodinated contrast.

Among patients with no underlying risk factors and/or diabetic patients with normal kidney function and no other risk factors, the risk for CIAKI is very low (i.e., < 1-2%). Among patients undergoing angiography with eGFR values < 60 ml/min/1.73m2, particularly with diabetes, the risk for a rise in SCr >= 0.5 mg/dL and/or 25% is higher and increases inversely with eGFR level. One past study of patients undergoing non-emergent angiography with pre-procedure eGFR < 60 ml/min/1.73m2 found an incidence of CIAKI of 8-13%. Among a similar population of patients undergoing non-emergent computed tomography, the risk ranged from 3.5-6.5%. However, < 1% of patients with eGFR > 45 ml/min/1.73 m2 undergoing non-emergent outpatient computed tomography developed CIAKI. The risk for CIAKI that requires renal replacement therapy after any type of procedure is very low.


Multiple studies have examined the short- and long-term outcomes associated with the development of CIAKI. A very small proportion of patients who develop CIAKI (~ 1-2%) will require renal replacement therapy. While in-hospital death is similarly very uncommon following the development of CIAKI, multiple studies, largely retrospective in nature, have demonstrated that CIAKI is strongly associated with an increased risk for short- and long-term mortality. Whether CIAKI is the proximate cause of increased mortality or represents a biochemical marker of patients at higher risk is not known.

CIAKI commonly increases hospital duration of stay and has been associated with increased health resource utilization. Economic analyses suggest that a single episode of CIAKI carries a one-year cost of over $11,800.

Recent data link CIAKI with persistent renal injury at 3 months following contrast exposure as well as an increase in the rate of decline of kidney function over longer-term follow-up.

Special considerations for nursing and allied health professionals.

Radiology technicians and cardiac and non-cardiac angiography suite personnel should standardize the approach to identifying high-risk patients.

What is the evidence?

“Section 4: Contrast-Induced AKI”. Kidney Int Suppl.. vol. 2. 2012 Mar. pp. 1-138.

Morcos, SK, Thomsen, HS, Webb, JA. “Contrast media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR)”. Eur Radiol.. vol. 9. 1999. pp. 1602-1613.

McCullough, PA. “Contrast-induced acute kidney injury”. J Am Coll Cardiol.. vol. 51. 2008. pp. 1419-1428.

Weisbord, SD, Mor, MK, Resnick, AL, Hartwig, KC, Sonel, AF, Fine, MJ, Palevsky, PM. “Prevention, incidence, and outcomes of contrast-induced nephropathy”. Archives of Internal Medicine. vol. 168. 2008. pp. 1325-1332.

Weisbord, SD, Palevsky, PM. “Strategies for the prevention of contrast-induced acute kidney injury”. Current Opinion in Nephrology and Hypertension.. vol. 19. 2010. pp. 539-549.