B. Renal adverse reactions (post-contrast acute kidney injury, PC-AKI)

B. RENAL ADVERSE REACTIONS (POST-CONTRAST ACUTE KIDNEY INJURY, PC-AKI)

B.1. Measurement of renal function

B.2. Renal adverse reactions to iodine-based contrast media

B.2.1. Time of referral

B.2.2. Before the examination

B.2.3. Time of examination

B.2.4. After the examination

B.2.5. Multiple myeloma patients

B.3. Renal adverse reactions to gadolinium-based contrast agents

B.4. Patients with diabetes mellitus taking metformin

B.4.1. Iodine-based contrast media

B.4.2. Gadolinium-based contrast agents

B.5. Dialysis and contrast medium administration

B.6. Can iodine- and gadolinium-based contrast agents safely be given on the same day for routine examinations?

B.7. How long should there be between two iodine-based contrast media injections for routine examinations?

B.8. How long should there be between two gadolinium-based contrast agent injections for routine examinations?

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B. RENAL ADVERSE REACTIONS (POST-CONTRAST ACUTE KIDNEY INJURY, PC-AKI)

Definitions:

Post-contrast acute kidney injury (PC_AKI) is defined as an increase in serum creatinine > 0.3 mg/dl (or > 26.5 µmol/l), or > 1.5 times baseline, within 48-72 hours of intravascular administration of a contrast agent.

Intra-arterial injection with first pass renal exposure indicates that contrast agent reaches the renal arteries in a relatively undiluted form, e.g. injection into the left heart, thoracic and suprarenal abdominal aorta or the renal arteries.

Intra-arterial injection with second pass renal exposure indicates that contrast agent reaches the renal arteries after dilution either in the pulmonary or peripheral circulation, e.g. injection into the right heart, pulmonary artery, carotid, subclavian, coronary, mesenteric or infra-renal arteries.

B.1. MEASUREMENT OF RENAL FUNCTION

• Estimated glomerular filtration rate (eGFR), calculated from the serum creatinine, is the recommended method to estimate renal function before contrast agent administration.
• In adults > 18 years the CKD-EPI formula is recommended to calculate eGFR.

eGFR (ml/min/1.73 m²) =

Female sCr < 62 µmol/l: 144 x (sCr / 62)^-0.329 x 0.993^Age

Female sCr > 62 µmol/l: 144 x (sCr / 62)^-1.209 x 0.993^Age

Male sCr < 80 µmol/l: 141 x (sCr / 80)^-0.411 x 0.993^Age

B.2. RENAL ADVERSE REACTIONS TO IODINE-BASED CONTRAST MEDIA

RISK FACTORS FOR PC-AKI
Patient related	eGFR less than 45 ml/min/1.73 m2 before intra-arterial contrast medium administration with first pass renal exposure or in ICU patients. eGFR less than 30 ml/min/1.73 m2 before intravenous contrast medium or intra-arterial contrast medium administration with second pass renal exposure. Known or suspected acute renal failure.
Procedure related	Intra-arterial contrast medium administration with first pass renal exposure. Large doses of contrast medium given intra-arterially with first pass renal exposure. High-osmolality contrast media. Multiple contrast medium injections within 48-72 hours.

B.2.1. Time of Referral

ELECTIVE EXAMINATION

MEASUREMENT OF RENAL FUNCTION

• Measure eGFR before administering intravascular iodine-based contrast medium

Either

(a) In all patients

or

(b) In patients who have a history of

- Renal disease (eGFR < 60 ml/min/1.73 m²)

- Kidney surgery

- Proteinuria

- Hypertension

- Hyperuricemia

- Diabetes mellitus

• Timing of eGFR measurement

- Within 7 days before contrast medium administration in patients with an acute disease, an acute deterioration of a chronic disease or who are hospital inpatients.

- Within 3 months before contrast medium administration in all other patients.

EMERGENCY EXAMINATION

Identify at-risk patients (see above) if possible:

• Determine eGFR if the procedure can be deferred until the result is available without harm to the patient.
• If eGFR cannot be obtained, follow the protocols for patients with eGFR less than 45 ml/min/1.73 m² for intra-arterial administration with first pass renal exposure and eGFR less than 30 ml/min/1.73 m² for intravenous administration and intra-arterial administration with second pass renal exposure as closely as clinical circumstances permit.

B.2.2. Before the Examination

ELECTIVE EXAMINATION
At-risk patients (see above)	Consider an alternative imaging method not using iodine-based contrast media. Intravenous saline and bicarbonate protocols have similar efficacy for preventive hydration. For intravenous contrast medium and intra-arterial contrast medium administration with second pass renal exposure hydrate the patient either (a) with intravenous sodium bicarbonate 1.4 % (or 154 mmol/l in dextrose 5 % water): 3 ml/kg/h for 1 hour before contrast medium or (b) with intravenous saline 0.9 % 1 ml/kg/hr for 3-4 hours before and 4-6 hours after contrast medium. For intra-arterial contrast medium administration with first pass renal exposure hydrate the patient either with (a) intravenous sodium bicarbonate 1.4 % (or 154 mmol/l in dextrose 5 % water): 3 ml/kg/h for 1 hour before followed by 1 ml/kg/hr for 4-6 hours after contrast medium or (b) with intravenous saline 0.9 % for 3-4 hours before and 4-6 hours after contrast medium. The clinician responsible for patient care should individualize preventive hydration in patients with severe congestive heart failure (NYHA grade 3-4) or patients with end-stage renal failure (eGFR < 15 ml/min/1.73 m2). Oral hydration is not recommended as the sole method of preventive hydration.
EMERGENCY EXAMINATION
At-risk patients (see above)	Consider an alternative imaging method not using iodine-based contrast media. Use preventive hydration before contrast medium administration (see 'Elective examination' for protocols).

B.2.3. Time of examination

All patients	Use low- or iso-osmolar contrast media. Use the lowest dose of contrast medium consistent with a diagnostic result. For intra-arterial contrast medium administration with first pass renal exposure, keep either the ratio CM dose (in gram l) / absolute eGFR (in ml/min) < 1.1 or the ratio CM volume (in ml) / eGFR (in ml/min/1.73 m2) < 3.0, when using contrast medium concentration of 350 mgl/ml.

B.2.4. After the Examination

At-risk patients

Continue preventive hydration if appropriate (see protocols above). Determine eGFR 48 hours after contrast medium administration. If at 48 hours there is a diagnosis of PC-AKI, monitor the patient clinically for at least 30 days and determine eGFR at regular intervals.

Note: No pharmacological prophylaxis (with statins, renal vasodilators, receptor antagonists of endogenous vasoactive mediators or cytoprotective drugs) has been shown to offer consistent protection against PC-AKI.

B.2.5. Multiple myeloma patients

• Multiple myeloma patients with normal renal function are not at increased risk of PC-AKI provided that they are well hydrated and that low- or iso-osmolar iodine-based contrast media are used.
• Multiple myeloma patients often have reduced renal function, and such patients are at increased risk of PC-AKI.
• Multiple myeloma patients often have hypercalcemia which can increase the risk of kidney damage. Correction of hypercalcemia before contrast medium administration should be discussed with the hematologist.
• Assessment for Bence Jones proteinuria before contrast medium administration is not necessary.

B.3. RENAL ADVERSE REACTIONS TO GADOLINIUM-BASED CONTRAST MEDIA

MR-EXAMINATIONS

• The risk of PC-AKI is very low when gadolinium-based contrast agents are used in approved doses.
• In patients with reduced renal function refer to ESUR guidelines on NSF, A.3.2.

RADIOGRAPHIC EXAMINATIONS

• Gadolinium-based contrast agents are not approved for radiographic examinations.
• Gadolinium-based contrast agents should not be used for radiographic examinations in patients with renal impairment (eGFR < 60 ml/min/1.73 m²).
• Gadolinium-based contrast agents are more nephrotoxic than iodine-based contrast media in equivalent X-ray attenuating doses.

B.4. PATIENTS WITH DIABETES MELLITUS TAKING METFORMIN

B.4.1. Iodine-based contrast media

1. Patients with eGFR > 30 ml/min/1.73 m² and no evidence of AKI, receiving either intravenous contrast medium or intra-arterial contrast medium with second pass renal exposure: continue taking metformin normally.
2. Patients

(a) with eGFR < 30 ml/min/1.73 m² receiving intravenous contrast medium, or intra-arterial contrast medium with second pass renal exposure.

(b) Receiving intra-arterial contrast medium with first pass renal exposure.

(c) With AKI: stop taking metformin from the time of contrast medium administration. Measure eGFR within 48 hours and restart metformin if renal function has not changed significantly.

B.4.2. Gadolinium-based contrast media

No special precautions are necessary when diabetic patients on metformin are given gadolinium-based contrast agents as the risk of PC-AKI is very low.

B.5. DIALYSIS AND CONTRAST MEDIUM ADMINISTRATION

All iodine- and gadolinium-based contrast agents can be removed by hemodialysis or peritoneal dialysis. However, there is no evidence that hemodialysis protects patients with impaired renal function from post contrast acute kidney injury or nephrogenic systemic fibrosis.

In all patients, avoid osmotic and fluid overload.

To avoid the risk of NSF refer to A.3.2.

PATIENTS ON DIALYSIS
Patients on hemodialysis	Iodine-based contrast medium Correlation of time of the contrast medium injection with the hemodialysis session is unnecessary. Extra hemodialysis session to remove contrast medium is unnecessary. Gadolinium-based contrast agent Correlation of time of the contrast agent injection with the hemodialysis session is recommended. Extra hemodialysis session to remove contrast agent as soon as possible after it has been administered is recommended.
Patients on continuous ambulatory peritoneal dialysis	Iodine-based contrast medium Hemodialysis to remove the contrast medium is unnecessary. Gadolinium-based contrast agent The need for hemodialysis should be discussed with the referring physician.

B.6. CAN IODINE- AND GADOLINIUM-BASED CONTRAST AGENTS SAFELY BE GIVEN ON THE SAME DAY FOR ROUTINE EXAMINATIONS?

Efficient practice may involve giving iodine- and gadolinium-based contrast agents for enhanced CT and MR on the same day. To reduce any potential for nephrotoxicity the following are recommended:

1. Patients with normal renal function or moderately reduced (GFR > 30 ml/min/1.73 m²).
   75 % of both gadolinium- and iodine-based contrast agents are excreted by 4 hours after administration. There should be 4 hours between injections of iodine- and gadolinium-based contrast agents.
2. Patients with severely reduced renal function (GFR < 30 ml/min/1.73 m² or on dialysis).
   There should be 7 days between injections of iodine- and gadolinium-based contrast agents.

Note: Gadolinium-based contrast agents attenuate X-rays well and may be misinterpreted on CT when they have been excreted into the urinary tract. For abdominal examinations, enhanced CT should be done before enhanced MR. For chest and brain examinations, either CT or MR may be done first.

B.7. HOW LONG SHOULD THERE BE BETWEEN TWO IODINE-BASED CONTRAST MEDIUM INJECTIONS FOR ROUTINE EXAMINATIONS?

1. Patients with normal or moderately reduced renal function (GFR > 30 ml/min/1.73 m²).
   75 % of iodine-based contrast medium is excreted by 4 hours after administration. There should be 4 hours between injections of iodine-based contrast medium.
2. Patients with severely reduced renal function (GFR < 30 ml/min/1.73 m²).
   There should be 48 hours between injections of iodine-based contrast medium.
3. Patients on dialysis.
   If there is remnant renal function there should be at least 48 hours between injections of iodine-based contrast medium.

B.8. HOW LONG SHOULD THERE BE BETWEEN TWO GADOLINIUM-BASED CONTRAST AGENT INJECTIONS FOR ROUTINE EXAMINATIONS?

1. Patients with normal or moderately reduced renal function (GFR > 30 ml/min/1.73 m²).
   75 % of extracellular gadolinium-based contrast agents are excreted by 4 hours after administration. There should be 4 hours between injections of gadolinium-based contrast agent.
2. Patients with severely reduced renal function (GFR < 30 ml/min/1.73 m²) or on dialysis.
   There should be 7 days between injections of gadolinium-based contrast agent.