What are the risks of using Gadolinium (Gadolinium-based contrast agent) contrast dye in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Gadolinium-based contrast agents (GBCAs) should be used with caution in patients with chronic kidney disease (CKD), particularly those with estimated glomerular filtration rates (eGFR) below 30 mL/min/1.73m², and the potential harms of delaying or withholding GBCAs for an MRI in these patients may outweigh the risk of nephrogenic systemic fibrosis (NSF) in most clinical situations. The risk of NSF with group II GBCAs is extremely low, even in patients with eGFR < 30 mL/min per 1.73 m2 or acute kidney injury (AKI) 1.

Key Considerations

• The American College of Radiology and the National Kidney Foundation recommend the use of group II GBCAs, which have a very low risk of NSF, in patients with CKD 1.
• The risk of NSF increases with larger doses of group I GBCAs, but the dose-related risk of NSF from group II and group III GBCAs is unknown 1.
• Kidney function screening is optional for group II GBCAs, but it is necessary for group III GBCAs 1.
• The KDIGO 2024 clinical practice guideline recommends the use of American College of Radiology group II and III GBCAs in people with GFR <30 ml/min per 1.73 m2 (CKD G4–G5) who require gadolinium-containing contrast media 1.

Recommendations

• If contrast is absolutely necessary for diagnostic purposes in patients with CKD, macrocyclic GBCAs such as gadoterate meglumine (Dotarem), gadobutrol (Gadavist), or gadoteridol (ProHance) are preferred at the lowest possible dose because they have greater stability and lower risk of complications.
• Prior to administration, patients should be well-hydrated, and nephrology consultation is recommended.
• For patients requiring regular imaging, alternative non-contrast techniques such as MRI without contrast, ultrasound, or CT without iodinated contrast should be considered whenever clinically appropriate.

From the FDA Drug Label

5.5 Acute Kidney Injury In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging. 5.5 Acute Renal Failure In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred with the use of gadolinium-based contrast agents. The risk of renal failure may increase with increasing dose of the contrast agent.

The risks of using Gadolinium-based contrast agents in patients with Chronic Kidney Disease (CKD) include:

• Acute Kidney Injury: requiring dialysis
• Acute Renal Failure: requiring dialysis or worsening renal function To minimize these risks, it is recommended to:
• Screen all patients for renal impairment by obtaining a history and/or laboratory tests
• Administer the lowest dose necessary for adequate imaging
• Consider follow-up renal function assessments for patients with a history of renal dysfunction 2 3

From the Research

Risks of Gadolinium-Based Contrast Agents in CKD Patients

The use of Gadolinium-based contrast agents (GBCAs) in patients with Chronic Kidney Disease (CKD) has been associated with several risks, including:

• Nephrogenic systemic fibrosis (NSF), a progressive and potentially fatal multiorgan system fibrosing disease 4, 5
• Gadolinium deposition in brain and a possible systemic syndrome attributed to GBCAs 6
• Nephrotoxicity, although the risk is considered minimal in patients with an estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 7

Factors Increasing the Risk of NSF

The risk of developing NSF is increased by:

• Larger doses of gadolinium or multiple exposures 5
• Exposure to specific gadolinium chelates (non-ionic, linear) 5
• Underlying pro-inflammatory states (in particular vascular endothelial dysfunction) 5
• Severe acute kidney injury (AKI) or advanced chronic kidney disease (stages 4 and 5) not requiring dialysis 5

Recommendations for GBCA Use in CKD Patients

• In patients with mild-to-moderate CKD (eGFR ≥30 and <60 mL/min/1.73 m2), administration of standard doses of GBCA is safe and no additional precautions are necessary 8
• In patients with AKI, with severe CKD (eGFR <30 mL/min/1.73 m2), or on dialysis, administration of GBCAs should be considered individually and alternative imaging modalities utilized whenever possible 8
• If GBCAs are necessary, newer GBCAs may be administered with patient consent obtained by a physician (or their delegate), citing an exceedingly low risk (much less than 1%) of developing NSF 8

Prevention and Treatment of NSF

• Avoidance of gadolinium exposure appears to be the best approach for patients who maintain risk factors 5
• Aggressive hemodialysis following exposure may be useful as gadolinium is efficiently removed by this extracorporeal technique 5
• No clearly effective therapies exist for NSF, although recovery from AKI and establishment of normal kidney function with renal transplantation appear to reverse or stabilize the disease in some cases 5