Nephrology Hypertension

Acute Kidney Injury: Contrast Nephrotoxicity

Also known as: contrast nephropathy; contrast-induced nephropathy; radiocontrast nephropathy

Related conditions: acute kidney injury, acute renal failure

Does this patient have contrast-associated acute kidney injury?

Description of the problem

Contrast-associated acute kidney injury (CA-AKICA-AKI) is characterized by an abrupt decline in kidney function following the intravascular administration of iodinated contrast media. CA-AKI 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 occurs 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 < 10meq/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.

Tubular epithelial cell and granular "muddy brown" casts are often seen on urine microscopy, as CA-AKI represents a form of acute tubular necrosis.

Complications of progressive or severe CA-AKI 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

How should patients with contrast nephrotoxicity be managed?

Emergency management

Emergency management of CA-AKI 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, sodium polystyrene sulfonate). Renal replacement therapy may be required in severe and/or refractory cases

  2. Volume overload/pulmonary edema - Intravenous 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


CA-AKI 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 CA-AKI

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 CA-AKI. Atheroembolic disease is often accompanied by extra-renal organ involvement (e.g., central nervous system [CNS], gastrointestinal [GI], skin). Clinical features of atheroembolic renal disease not present in CA-AKI include hypocomplementemia and livedo reticularis.

Pre-renal AKI

Pre-renal AKI is due to decreased absolute or effective circulating volume and reduced renal perfusion. As may occur with CA-AKI, pre-renal AKI is characterized by low urine Na and FeNa. Unlike CA-AKI, 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.

Alternative causes of acute tubular necrosis (ATN)

Ischemic (e.g., 2o hypotension), other nephrotoxic medications including aminoglycosides

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

Specific treatment

CA-AKI 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

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 non-steroidal anti-inflammatory agents) prior to contrast administration and withhold until confirmation made that CA-AKI 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 day following the contrast-enhanced procedure (see below for recommendations on dosing). While data supporting the effectiveness of NAC for the prevention of CA-AKI are inconclusive, the oral formulation of this agent is generally safe and inexpensive. Therefore, until adequately powered trials conclusively define the role of this anti-oxidant, 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 CA-AKI 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 increased risk of CA-AKI 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 patients' risk for CA-AKI, use of this medication in a patient who develops CA-AKI increases the risk for life-threatening metabolic acidosis. Once confirmation is made that CA-AKI 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 provision of alternative hypoglycemic therapy as appropriate and in consultation with the primary provider.

Data on the discontinuation of angiotensin converting enzyme inhibitors (ACEI) 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 CA-AKI: aminophylline, theophylline, HMG Co-A reductase inhibitors (statins), prostaglandin analogs, ascorbic acid, calcium channel blockers, hemofiltration. There are currently insufficient data to recommend the use of these interventions to prevent CA-AKI.

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

N-acetylcysteine - consider 1200 mg po twice daily on day of and day following the contrast-enhanced procedure. Preliminary data suggest that a dose of 1200 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 to 12 hours prior to and 6 to 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 to 6 hours following contrast administration.

Disease monitoring, follow-up and disposition

Monitoring for the development of CA-AKI 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 CA-AKI). 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, be instructed to avoid any other nephrotoxic insults, and followed for the development of clinical and/or serological complications of acute kidney injury.

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.

What happens to patients with contrast nephrotoxicity?


The pathophysiology of CA-AKI 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 CA-AKI varies considerably based on three principal factors:

Definition of CA-AKI - the most commonly used definition of CA-AKI 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 CA-AKI.

Underlying risk - among patients with no underlying risk factors, the incidence of CA-AKI is exceedingly low. Among patients at higher risk for CA-AKI (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.

Type of procedure - the observed incidence of CA-AKI 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 CA-AKI 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 CA-AKI of 8% to13%. Among a similar population of patients undergoing non-emergent computed tomography, the risk ranged from 3.5% to 6.5%. However, < 1% of patients with eGFR > 45 ml/min/1.73 m2 undergoing non-emergent outpatient computed tomography developed CA-AKI. The risk for CA-AKI 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 CA-AKI. A very small proportion of patients who develop CA-AKI (~ 1-2%) will require renal replacement therapy. While in-hospital death is similarly very uncommon following the development of CA-AKI, multiple studies, largely retrospective in nature, have demonstrated that CA-AKI is strongly associated with an increased risk for short- and long-term mortality. Whether CA-AKI is the proximate cause of increased mortality or represents a biochemical marker of patients at higher risk is not known.

CA-AKI commonly increases hospital duration and has been associated with increased health resource utilization. Economic analyses suggest that a single episode of CA-AKI carries a 1-year cost of over $11,800.

Recent data link CA-AKI 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.

Preventive Therapy

Heinrich, MC, Häberle, L, Müller, V, Bautz, W, Uder, M. "Nephrotoxicity of iso-osmolal iodixanol compared with nonionic low-osmolal contrast media: meta-analysis of randomized controlled trials". Radiology. vol. 250. 2009. pp. 68-86.

((This meta-analysis compares the comparative nephrotoxicity of iso-osmolal and low-osmolal contrast based on the findings of clinical trials.)

Weisbord, SD, Palevsky, PM. "Acute kidney injury: intravenous fluid to prevent contrast-induced AKI". Nat Rev Nephrol. vol. 5. 2009. pp. 256-257.

((This review discusses the role of intravenous fluids for the prevention of CA-AKI.)

Rihal, CS, Textor, SC, Grill, DE, Berger, PB, Ting, HH, Best, PJ, Singh, M, Bell, MR, Barsness, GW, Mathew, V, Garratt, KN, Holmes, DR. "Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention". Circulation. vol. 105. 2002. pp. 2259-2264.

((This study examines the incidence and outcomes associated with CA-AKI.)

McCullough, PA, Adam, A, Becker, CR, Davidson, C, Lameire, N, Stacul, F, Tumlin, J. "CIN Consensus Working Panel: Epidemiology and prognostic implications of contrast-induced nephropathy". Am J Cardiol. vol. 98. 2006. pp. 5K-13K.

((This article discusses the epidemiology and outcomes associated with CA-AKI.)

Weisbord, SD, Chen, H, Stone, RA. "Associations of increases in serum creatinine with mortality and length of hospital stay after coronary angiography". J Am Soc Nephrol. vol. 7. 2006. pp. 2871-2877.

((This study examines the associations of small increments in serum creatinine following angiography with mortality and length of stay.)

Goldenberg, I, Chonchol, M, Guetta, V. "Reversible acute kidney injury following contrast exposure and the risk of long-term mortality". Am J Nephrol. vol. 29. 2009. pp. 136-144.

((This study examined the association of CA-AKI with long-term risk of mortality.)

James, MT, Ghali, WA, Tonelli, M, Faris, P, Knudtson, ML, Pannu, N, Klarenbach, SW, Manns, BJ, Hemmelgarn, BR. "Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function". Kidney Int. vol. 78. 2010. pp. 803-809.

((This study examined the association of CA-AKI with long-term loss of kidney function.)

Subramaniam, RM, Suarez-Cuervo, C, Wilson, RF, Turban, S, Zhang, A, Sherrod, C, Aboagye, J, Eng, J, Choi, MJ, Hutfless, S, Bass, EB. "Effectiveness of prevention strategies for contrast-induced nephropathy: A systematic review and meta-analysis". Ann Intern Med. vol. 164. 2016. pp. 406-416.

((This is a systematic review and meta-analysis of strategies for prevention of AA-AKI. The most important finding from this analysis is that the strength of evidence for the majority of interventions discussed is low or insufficient).

Eng, J, Wilson, RF, Subramaniam, RM, Zhang, A, Suarez-Cuervo, C, Turban, S, Choi, MJ, Sherrod, C, Hutfless, S, Iyoha, EE, Bass, EB. "Compartive effect of contrast media type on the incidence of contrast-induced nephropathy: A systematic review and meta-analysis". Ann Intern Med. vol. 164. 2016. pp. 417-424.

((This systematic review and meta-analysis compares the comparative nephrotoxicity of iso-osmolal and low-osmolal contrast based on the findings of clinical trials).
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