Contrast-Induced Acute Kidney Injury (CI-AKI)

• Lisa Cohen, M.D.

 Basic Information

Definition

A rise in serum creatinine of 0.5 mg/dl or >25% elevation from baseline 48 hours after iodinated contrast media exposure (Table E1).

Synonyms

1. Contrast-induced nephropathy (CIN)

2. Contrast nephropathy

3. Radiocontrast-induced nephropathy

4. CI-AKI

ICD-10CM CODES
N14.1	Nephropathy induced by other drugs, medicaments, and biological substances

Epidemiology & Demographics

Incidence

The overall incidence of CI-AKI has been reported to be approximately 7%, and 11% of acquired AKI cases during hospitalization have been attributed to CK-AKI. However, recent retrospective studies using statistical techniques to minimize confounding factors suggest that CI-AKI incidence has been greatly overestimated.

Peak Incidence

Incidence rates vary widely in the literature—a result of discrepancies in type and dose of contrast media used, reason for the imaging study, and definition of CI-AKI. In one risk prediction model of CI-AKI, 24% of patients in the highest-risk decile undergoing percutaneous coronary intervention (PCI) developed CI-AKI. In another large, retrospective study using propensity-matched controls, no increased risk of acute kidney injury was seen in patients receiving CT with IV contrast compared with those not receiving CT.

Predominant Sex and Age

Risk of CI-AKI increases with age. There is no gender predilection.

Risk Factors

Patient-related factors include chronic kidney disease, age >75 years, diabetes mellitus if CKD is present, severe anemia, non-normovolemic states such as heart failure and volume depletion, and hemodynamic instability. Non-patient-related factors include contrast osmolality, use of ionic contrast (rarely used), contrast total dose and sequential doses, and requirement for intraaortic balloon pump. Although initially thought to be higher, the risk of CI-AKI does not increase with intraarterial contrast administration (e.g., cardiac catheterization) compared with intravenous contrast dosing (e.g., CT). Inpatients have a higher risk of developing CI-AKI than outpatients (Box E1 and Table E2).

BOX E1Recommendations to Reduce the Risk of Contrast-Induced Nephropathy

1. 1.

   Identify patients at risk for contrast-induced nephropathy (CIN) and calculate their total risk score.

2. 2.

   Assess risk/benefit of the proposed contrast-requiring intervention and consider alternative not requiring contrast intervention.

3. 3.

   Assess kidney function by estimated glomerular filtration rate (eGFR) or calculated creatinine clearance prior to contrast, especially in patients at risk for CIN.

4. 4.

   Modify correctable risk factors and hold medications that may act as co-nephrotoxins.

5. 5.

   In high-risk patients receiving intraarterial contrast, consider either a low-osmolar contrast medium (other than iohexol) or an iso-osmolar contrast agent.

6. 6.

   Use the lowest dose of appropriate contrast medium.

7. 7.

   In high-risk patients, correct hypovolemia. Stop diuretics and consider IV fluid if no contraindication exists. The optimal fluid type and quantity are not clear. Data support the use of either 0.9% saline or isotonic sodium bicarbonate, beginning at least 1 hour prior to contrast injection and continuing for at least 6 hours postinjection. Initial rates of 3 ml/kg/hr followed by 1 ml/kg/hr are commonly recommended. The patient should be monitored for signs and symptoms of hypervolemia or pulmonary edema.

8. 8.

   In high-risk patients, consider N-acetylcysteine, particularly if higher doses of contrast media or intraarterial administration is necessary. A total of 4 doses of N-acetylcysteine, 1200 mg orally twice a day, starting the day prior to contrast injection, is an acceptable regimen. For emergent procedures, consider 1200 mg IV as an initial dose followed by the aforementioned 4 doses.

9. 9.

   In patients with advanced kidney disease, prophylactic hemofiltration before and after contrast was associated with reduced mortality in one study.

10. 10.

    In high-risk patients, serum creatinine should be rechecked within 24 to 72 hours post contrast injection.

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

Physical Findings & Clinical Presentation

1. •

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

Etiology

1. •

   Nephrotoxicity occurs due to renal medullary ischemia, a result of vasoconstrictive effects of the contrast medium on the large and small renal arteries.

2. •

   Contrast also exerts a direct cytotoxic effect on the vascular endothelium and renal tubular cells, leading to cell injury and death due to generation of damaging reactive oxygen species.

    

Diagnosis

Differential Diagnosis

1. •

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

Workup

1. •

   Diagnosis is dependent primarily 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 ATN).

2. •

   Urinalysis often reveals a fractional excretion of sodium (FE_Na) of <1% despite acute tubular necrosis. 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 may be seen on urinalysis.

3. •

   A renal biopsy is not recommended for diagnostic confirmation, since biopsy findings are nonspecific for acute tubular necrosis.

Laboratory Tests

1. •

   Creatinine, urinalysis, and urine microscopy

2. •

   Urine and plasma sodium and creatinine concentrations for determination of FE_Na

Imaging Studies

1. •

   No radiologic tests aid in the diagnosis of CI-AKI. A renal ultrasound should be obtained if postrenal obstruction is in the differential diagnosis.

Treatment

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

Recommended strategies for CI-AKI prophylaxis:

1. •

   Avoidance of studies and procedures using intravenous contrast, if not emergent. Consider an alternative imaging modality, if available, for patients at high risk for developing CIN.

2. •

   Use low-osmolar nonionic contrast media.

3. •

   Minimize contrast volume (dose).

4. •

   Volume expansion with intravenous isotonic fluid. Normal saline and sodium bicarbonate solutions are both effective in reducing the risk of CIN, and normal saline is more effective than 0.45% saline. Although sodium bicarbonate solutions were initially thought to be superior to saline, current evidence reveals that neither solution is superior.

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

1. •

   Oral hydration solutions

2. •

   Prophylactic hemodialysis or hemofiltration

3. •

   Diuresis from diuretic medications or by osmotic diuretics (e.g., mannitol)

4. •

   Vasodilators (e.g., fenoldopam, nifedipine, theophylline)

5. •

   Ascorbic acid

Preventive measures for CI-AKI that may provide modest additional benefit include N-acetylcysteine (given at high dose with intravenous fluids), HMG Co-A reductase inhibitors (statins), and repeat ischemia-reperfusion injury techniques.

General Prophylaxis: Intravenous Hydration

1. •

   Outpatients with glomerular filtration rate (GFR) <60 ml/min: withhold medications that reduce GFR (e.g., nonsteroidal antiinflammatory drugs and, possibly, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) or extracellular fluid volume (e.g., thiazide or loop diuretics). An outpatient hydration protocol with either normal saline or sodium bicarbonate may be considered, particularly with GFR <45 ml/min. Notably, outpatient hydration protocols have not been rigorously evaluated. Sodium bicarbonate infused at 3 ml/kg/hr for 1 hour preprocedure and 1.5 mg/kg/hr 4 to 6 hours intra- and postprocedure can be performed in the outpatient setting.

2. •

   Inpatients with GFR <60 ml/min: intravenous normal saline or D5W with 3 amps sodium bicarbonate at 1 ml/kg/hr for 6 to 12 hours preprocedure, during the procedure, and 6 to 12 hours postprocedure. With contraindications to intravenous fluid administration (e.g., congestive heart failure with pulmonary edema), consider postponement of studies involving contrast medium, if not emergently indicated. If the procedure is unavoidable, fluid management should be tailored to the individual patient.

Disposition

1. •

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

Referral

1. •

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

Pearls & Considerations

1. •

   A diagnosis of CI-AKI should be considered in patients who develop acute kidney injury 24 to 72 hours after contrast exposure. Urine sediment may be bland or show signs of tubular injury. FE_Na is often <1% due to vasoconstriction.

2. •

   Administration of isotonic intravenous fluids as a preventive measure is indicated for patients with GFR <60 ml/min or who otherwise are at high risk for CI-AKI. Statins may also have preventative effects.

3. •

   ACE inhibitors, NSAIDs, and other potential nephrotoxic drugs should be avoided in patients receiving intravenous contrast media.

4. •

   Diabetic patients should have metformin held before receiving intravenous contrast due to an increased risk of metformin-related lactic acidosis in the setting of CI-AKI.

Suggested Readings

• L. Luk, et al.: Intravenous contrast-induced nephropathy: the rise and fall of a threatening idea. Adv Chron Kidney Dis. 24 (3):169–175 2017

• P. McCullough, et al.: Contrast-induced acute kidney injury. J Am Coll Cardiol. 68 (13):1465–1473 2016 27659469

• J.S. McDonald, et al.: Frequency of acute kidney injury following intravenous contrast administration: a systematic review and meta-analysis. Radiology. 267 (1):106–118 2013 23360742

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