Contrast Associated Acute Kidney Injury

An increase of serum creatinine of >0.5 mg/dl or >25% from baseline that occurs within 48 hr after iodinated contrast media (CM) administration.

Classification of Iodinated Contrast Media

Adapted from Vincent JL et al: Textbook of critical care, ed 6, Philadelphia, 2011, Saunders.

Chemical Property	Relative Osmolality	Contrast Agent	Osmolality (mOsm/kg H ₂O)
Ionic	High osmolality	Diatrizoate	1500-1860
Ioxithalamate
Ioxithalamate
Ionic	Low osmolality	Ioxaglate	600
Nonionic	Low osmolality	Iobitridol	521-695
Iohexol
Iomeprol
Iopamidol
Iopromide
Ioversol
Nonionic	Iso-osmolal	Ioxaglate	270-320
Iotrolan
Iodixanol

Synonyms

Contrast-induced nephropathy (CIN)
Contrast nephropathy
Radiocontrast-induced nephropathy (RCIN)
Contrast-induced acute kidney injury (CI-AKI)

Epidemiology & Demographics

Nomenclature

•The term contrast-induced AKI (CI-AKI), formerly called contrast-induced nephropathy (CIN), implies that contrast medium is the sole etiologic factor of AKI during circumstances of contrast administration. However, frequently, multiple potential etiologic factors are present. The term CI-AKI should only be used when contrast medium administration is the sole putative risk factor for development of AKI. Thus, the term, contrast-associated AKI (CA-AKI) is more appropriate in the majority of cases of AKI that occur in the context of CM administration. Therefore, CI-AKI is a subset of CA-AKI, which encompasses any AKI occurring with 48 hr of CM administration.
•Low osmolar CM (LOCM) are hyperosmolar (∼600 mOsm/kg H₂O) relative to isosmolar CM (IOCM; ∼290 mOsm/kg) and serum (∼285 mOsm/kg H₂O to 295 mOsm/kg H₂O). The dimeric structure of IOCM renders them more viscous than LOCM. The majority of contemporary iodinated CM are categorized as LOCM. High osmolar iodinated CM (HOCM) have greater osmolalities than LOCM and IOCM. HOCM have been replaced by LOCM and IOCM for intravenous (IV) administration in modern clinical practice.

Incidence

The overall incidence of CA-AKI is reported as approximately 7%, and 11% of acquired AKI cases during hospitalization have been attributed to CA-AKI. However, recent retrospective studies using statistical techniques to minimize confounding factors suggest that CA-AKI incidence has been greatly overestimated. The following opinions and recommendations apply to IV, e.g., contrast-enhanced CT, versus intra-arterial (e.g., coronary artery angiography) CM administration. The latter has unique considerations that do not apply to IV CM administration (e.g., requirement for arterial access, atheroembolic complications, and population-specific AKI risk factors).

Predominant Sex and Age

Current controversies regarding the true incidence of CA-AKI call into question the relationship of age to CA-AKI risk. The frequency of CA-AKI appears to increase with age, but age may in fact be simply a risk factor for other causes of AKI that occur in patients receiving CM, in particular, declining glomerular filtration rate (GFR). There is no sex predilection for CA-AKI.

Peak Incidence

Incidence rates of CA-AKI vary widely in the literature, the result of discrepancies in type and dose of CM used, rationale for ordering the imaging study, and varying definitions of CA-AKI. In one risk prediction model of CA-AKI, 24% of patients in the highest-risk decile undergoing percutaneous coronary intervention (PCI) developed CA-AKI. In another large, retrospective study using propensity-matched controls, no increased risk of AKI occurred in patients who received CT with IV contrast compared to patients who did not receive CT.

Risk Factors

Patient-related factors include chronic kidney disease (CKD) with an estimated glomerular filtration rate <30 ml/min per 1.73 m² (CKD stage 4 or greater), age >75 yr, diabetes mellitus with CKD, albuminuria, nonnormovolemic states such as heart failure and volume depletion, and hemodynamic instability. Non–patient-related factors include contrast osmolality, exposure to ionic contrast (rarely used), total contrast dose, sequential CM dosing, concomitant exposure to nephrotoxic agents, and requirement for an intra-aortic balloon pump treatment. It is unclear if intra-arterial CM administration (e.g., cardiac catheterization) bears greater risk for AKI than IV CM administration (e.g., CT). Inpatients have a higher risk of developing CA-AKI than outpatients.

Recommendations to Reduce the Risk of Contrast-Associated–AKI

Adapted from Vincent JL et al: Textbook of critical care, ed 6, Philadelphia, 2011, Saunders.

CM, Contrast media; IV, intravenous.

1.Identify patients at risk for CA-AKI.
2.Assess the risk-to-benefit ratio of the proposed contrast medium-requiring intervention. Consider alternatives to procedures or imaging that requires iodinated contrast. Do not withhold IV contrast in emergent situations where administration of contrast is necessary for optimal patient care, i.e., risk-to-benefit ratio is justifiable.
3.Assess kidney function by estimated glomerular filtration rate (eGFR) or calculated creatinine clearance before contrast, especially in patients at risk for CA-AKI.
4.Modify correctable risk factors and withhold medications that may increase risk of nephrotoxicity, i.e., withhold nonsteroidal antiinflammatory agents at least 48 hr prior to contrast exposure.
5.Use the lowest dose of appropriate contrast medium.
6.In high-risk patients, correct hypovolemia. Stop diuretics and consider IV fluid if no contraindication exists. Heart failure patients should not have diuretics withheld or discontinued unless volume depleted.
7.Intravenous, isotonic fluid expansion with either 0.9% saline or isotonic sodium bicarbonate solution (150 mM). The optimal fluid type and quantity have not been definitively determined. Volume expansion generally begins 1 hr precontrast administration and continues for 3-12 hr postcontrast delivery. Typical regimens are those of fixed volumes (e.g., 500 ml before and after CM delivery) or weight-based (1-3 ml/kg per hr). Longer regimens (∼12 hr) have been shown to lower the risk of CA-AKI compared to shorter regimens. The patient should be monitored for signs and symptoms of hypervolemia or pulmonary edema.
8.The decision to continue or withhold renin-angiotensin-aldosterone system (RAAS) inhibitors prior to a contrast study is controversial. However, given the lack of strong evidence supporting a benefit to continuing RAAS inhibitors, we recommend withholding these drugs in high-risk individuals for at least 48 hr before elective procedures.
9.N-acetylcysteine prophylaxis is not recommended.
10.Prophylactic hemodialysis or hemofiltration is not recommended.

Physical Findings & Clinical Presentation

Elevation in serum creatinine generally occurs 24 to 48 hr after administration of contrast. Typically, there are no accompanying symptoms or exam findings. AKI usually resolves within 10 days of radiocontrast exposure. Less than 1% of patients with CA-AKI will require dialysis, typically patients with a history of advanced kidney disease.

Etiology

•Nephrotoxicity occurs from the vasoconstrictive effect of CM on large and small renal arteries with consequent renal medullary ischemia.
•Contrast also exerts a direct cytotoxic effect on the vascular endothelium and renal tubular cells, leading to cell injury and death from reactive oxygen species.

Diagnosis

Differential Diagnosis

Acute tubular injury, atheroembolic renal disease (i.e., postcardiac catheterization), acute interstitial nephritis, prerenal azotemia

Workup

•Diagnosis is primarily dependent on history and laboratory values. A search for clinical findings more suggestive of other etiologies of AKI should be conducted (e.g., livedo reticularis or dusky lower-extremity digits in the presence of atheroembolic disease, evidence of systemic infection accompanied by hypotension in the case of sepsis-mediated acute tubular injury).
•Urinalysis often reveals a fractional excretion of sodium (FE_Na) of <1% despite acute tubular injury. A high urine specific gravity may reflect the filtration of hyperosmolar contrast medium. Markers of renal tubular damage including muddy brown granular casts or renal epithelial cells detected by urine microscopy.
•A kidney biopsy is not recommended to confirm diagnosis because histology is nonspecific for acute tubular injury. If the course of AKI is atypical, a biopsy may define the cause of AKI as atheroembolic disease or acute interstitial nephritis.

Laboratory Tests

•Serum creatinine, urinalysis, and urine microscopy
•Urine and serum sodium and creatinine levels for determination of FE_Na

Imaging Studies

No radiologic test establishes the diagnosis of CA-AKI. A renal ultrasound should be obtained if postrenal obstruction is part of the differential diagnosis.

Treatment

Treatment for CA-AKI is supportive. Prevention has been the focus of research efforts.

Recommended strategies for CA-AKI prophylaxis:

•Avoidance of studies and procedures using intravenous contrast, if not emergent. Consider an alternative imaging modality, if available, for patients at high risk for development of CIN.
•Use low-osmolar nonionic CM.
•Minimize contrast volume (dose).
•Volume expansion with intravenous isotonic fluid. Normal saline (0.9% saline) and sodium bicarbonate solutions are both effective in reducing the risk of CA-AKI.

Preventive measures for CA-AKI that have not shown significant benefit include:

•Oral hydration solutions
•Prophylactic hemodialysis or hemofiltration
•Diuresis from diuretic medications or by osmotic diuretics (e.g., mannitol)
•Vasodilators (e.g., fenoldopam, nifedipine, theophylline)
•Ascorbic acid
•N-acetylcysteine

General Prophylaxis: Intravenous Hydration

•Outpatients with glomerular filtration rate (GFR) <60 ml/min: Withhold medications that reduce GFR, e.g., nonsteroidal antiinflammatory drugs and, possibly, diuretics. An outpatient hydration protocol with either 0.9% saline or sodium bicarbonate may be considered, particularly with eGFRs <45 ml/min per 1.73 m². However, this approach is not required for ambulatory individuals undergoing an IV contrast study. Outpatient hydration protocols have not been rigorously evaluated and are not required prior to IV contrast studies.
•Inpatients with eGFRs <60 ml/min per 1.73 m²: Intravenous 0.9% saline or D₅W with 150 mM sodium bicarbonate at 1 ml/kg per hr for 6 to 12 hr preprocedure, during the procedure, and 6 to 12 hr postprocedure. With contraindications to intravenous fluid administration (e.g., congestive heart failure with pulmonary edema), consider postponement of studies involving CM, if not emergently indicated. If the procedure is unavoidable, fluid management should be tailored to the individual patient.

Disposition

CA-AKI is usually self-limited. Patients with severe renal functional impairment may require hospitalization for supportive care and potential dialysis.

Referral

Patients at high risk for CA-AKI or who develop significant CA-AKI should be referred to nephrology.

Pearls & Considerations

•Although there has been agreement that iodinated contrast dye has nephrotoxic effects, the true incidence of CA-AKI has been reconsidered due to the findings of several recent studies showing that intravenous contrast administration does not increase the risk of AKI in patients with other reasons for development of AKI. There is concern that potentially beneficial diagnostic contrast media-imaging studies or procedures are being withheld due to fears of developing CA-AKI.
•A diagnosis of CA-AKI can be considered in patients who develop AKI 24 to 72 hr after contrast exposure. Urine sediment may be bland or show signs of tubular injury. The FE_Na may be <1% due to altered renal hemodynamics.
•Administration of isotonic intravenous fluids is appropriate for CKD patients with eGFRs <30 ml/min per 1.73 m² or who are otherwise at high risk for CA-AKI.
•Nonsteroidal antiinflammatory drugs and other potential nephrotoxic drugs should be avoided in patients receiving intravenous contrast media. Metformin does not predispose to CA-AKI but should be discontinued if AKI occurs. There is no evidence-based guidance regarding continuation or withdrawal of ACEIs or ARBs before contrast administration. Clinical judgment is warranted.
•Diabetic patients should have metformin held before receiving intravenous contrast due to an increased risk of metformin-related lactic acidosis in the setting of CA-AKI.

Seek Additional Information

Davenport M.S., et al.: Use of intravenous iodinated contrast media in patients with kidney disease: consensus statements from the American College of Radiology and the National Kidney Foundation. Radiology 2020; 294 (3): pp. 660-668.
Ewing M.J., Eidt J.F.: Con: contrast-induced nephropathy—should we try to avoid contrast media in patients with chronic kidney disease? Nephrol Dial Transplant 2018; 33: pp. 1320-1322.
Luk L., et al.: Intravenous contrast-induced nephropathy: the rise and fall of a threatening idea. Adv Chron Kidney Dis 2017; 24 (3): pp. 169-175.
McCullough P., et al.: Contrast-induced acute kidney injury. J Am Coll Cardiol 2016; 68 (13): pp. 1465-1473.
McDonald J.S., et al.: Frequency of acute kidney injury following IV contrast administration: a systematic review and meta-analysis. Radiology 2013; 267 (1): pp. 106-118.
Windpessl M., Kronbichler A.: Pro: contrast-induced nephropathy—should we try to avoid contrast media in patients with chronic kidney disease? Nephrol Dial Transplant 2018; 33: pp. 1317-1319.

Contrast Associated Acute Kidney Injury