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Basic Information ⬇

AUTHORS: Jerry Yee, MD, MACP, FRCP, FASN, FNKF and Mark A. Perazella, MD, FASN, FNKF

Definition

An increase of serum creatinine of >0.5 mg/dl or >25% from baseline that occurs within 48 h after iodinated contrast media (CM) administration (Table E1).

TABLE E1 Classification of Iodinated Contrast Media

Chemical PropertyRelative OsmolalityContrast AgentOsmolality (mOsm/kg H2O)
IonicHigh osmolalityDiatrizoate1500-1860
Ioxitalamate
Ioxitalamate
IonicLow osmolalityIoxaglate600
NonionicLow osmolalityIobitridol521-695
Iohexol
Iomeprol
Iopamidol
Iopromide
Ioversol
NonionicIso-osmolalIoxaglate270-320
Iotrolan
Iodixanol

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

Synonyms

Contrast-induced nephropathy (CIN)

Contrast nephropathy

Radiocontrast-induced nephropathy (RCIN)

Contrast-induced acute kidney injury (CI-AKI)

ICD-10CM CODE
N14.1Nephropathy induced by other drugs, medicaments, and biological substances
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 h 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 HOCM have been replaced by LOCM and IOCM for intravenous (IV) administration in modern clinical practice.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, for example, contrast-enhanced computed tomography (CT), versus intraarterial (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 & 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. The difference is likely explained by the risk factors present in those getting intraarterial contrast for a coronary intervention.

Risk Factors

Patient-related factors include chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m2 (CKD stage 4 or greater), age >75 yr, diabetes mellitus with CKD, albuminuria, abnormal volemic states such as heart failure and volume depletion, and hemodynamic instability. Nonpatient-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 intraaortic balloon pump treatment. It is unclear if the intraarterial route of 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 (Box E1).

BOX E1 Recommendations to Reduce the Risk of Contrast-Associated Acute Kidney Injury

  • Identify patients at risk for CA-AKI.
  • 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 intravenous (IV) contrast in emergent situations where administration of contrast is necessary for optimal patient care, that is, risk-to-benefit ratio is justifiable.
  • Assess kidney function by estimated glomerular filtration rate (eGFR) or calculated creatinine clearance before contrast, especially in patients at risk for CA-AKI.
  • Modify correctable risk factors and withhold medications that may increase risk of nephrotoxicity, that is, withhold nonsteroidal antiinflammatory agents at least 48 h before contrast exposure.
  • Use the lowest dose of appropriate contrast medium.
  • 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.
  • 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 h precontrast administration and continues for 3-12 h 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/h). Longer regimens (∼12 h) 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.
  • The decision to continue or withhold renin-angiotensin-aldosterone system (RAAS) inhibitors before 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 h before elective procedures.
  • N-acetylcysteine prophylaxis is not recommended.
  • Prophylactic hemodialysis or hemofiltration is not recommended.

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

Physical Findings & Clinical Presentation

Elevation in serum creatinine generally occurs 24 to 48 h 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 and arterioles 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.
  • CM viscosity may play a role in pathogenesis. Low- and iso-osmolal radiocontrast is more viscous than high-osmolal CM.
  • CM may also cause tubular injury through an effect known as “osmotic nephropathy.”

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 (FENa) 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 FENa
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. An algorithm for the prevention and management of CI-AKI is illustrated in Fig. E1. Prevention has been the focus of research efforts.

Figure E1 Algorithm for the Prevention and Management of Contrast-Induced Acute Kidney Injury (AKI)

!!flowchart!!

ACS, Acute coronary syndromes; ALARA, as low as reasonably achievable; CI-AKI, contrast-induced acute kidney injury; CKD, chronic kidney disease; Cr, creatinine; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; HF, heart failure; IV, intravenous; L-FABP, L-type fatty-acid binding protein; LVEDP, left ventricular end-diastolic pressure; NGAL, neutrophil-associated lipocalin; NSAIDs, nonsteroidal antiinflammatory drugs; RASi, renin angiotensin system inhibitors; SCr, serum creatinine; TAVI, transcatheter aortic valve insertion; TIMP2∗IGFBP-7, tissue inhibitor of metalloproteinase-2 concentration multiplied by insulin-like growth factor binding protein-7 concentration.

Ronco C et al: Critical care nephrology, ed 3, Philadelphia, 2019, Elsevier.

Recommended strategies for CA-AKI prophylaxis:

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

General Prophylaxis: Intravenous Hydration

  • Outpatients with GFR <60 ml/min: Withhold medications that reduce GFR, e.g., NSAIDs 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 before intravenous contrast studies.
  • Inpatients with eGFRs <45 ml/min per 1.73 m2: Intravenous 0.9% saline or D5W with 150 mM sodium bicarbonate at 1 ml/kg/h for 6 to 12 h preprocedure, during the procedure, and 6 to 12 h 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 ⬆ ⬇

Related Content

Acute Kidney Injury (Related Key Topic)

Suggested Readings ⬆

  1. Davenport M.S. : Use of intravenous iodinated contrast media in patients with kidney disease: consensus statements from the American College of Radiology and the National Kidney FoundationRadiology. ;294:660-668, 2020.
  2. 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. ;33:1320-1322, 2018.
  3. Luk L. : Intravenous contrast-induced nephropathy: the rise and fall of a threatening ideaAdv Chron Kidney Dis. ;24:169-175, 2017.
  4. McCullough P. : Contrast-induced acute kidney injuryJ Am Coll Cardiol. ;68:1465-1473, 2016.
  5. McDonald J.S. : Frequency of acute kidney injury following IV contrast administration: a systematic review and meta-analysisRadiology. ;267:106-118, 2013.
  6. Novak J.E., Handa R. : Contrast nephropathy associated with percutaneous coronary angiography and interventionCardiol Clin. ;37:287-296, 2020.
  7. Windpessl M., Kronbichler A. : Pro: contrast-induced nephropathy-should we try to avoid contrast media in patients with chronic kidney disease?Nephrol Dial Transplant. ;33:1317-1319, 2018.