What contrast agent has an osmolarity similar to serum?

Iso-Osmolar Contrast Agent with Osmolarity Similar to Serum

Iodixanol is the iso-osmolar contrast agent with osmolarity equivalent to serum (approximately 290 mOsm/kg), making it the only truly iso-osmolar iodinated contrast medium available. 1, 2, 3

Contrast Agent Classification by Osmolarity

Iso-osmolar agents:

• Iodixanol is the sole iso-osmolar nonionic dimeric contrast agent with osmolality equal to serum 2, 3
• Osmolality approximately 290 mOsm/kg, matching physiologic serum osmolality 2

Low-osmolar agents (for comparison):

• Iopamidol, iopromide, iomeprol, ioversol, and iohexol are low-osmolar contrast media (LOCM) with osmolality 2-3 times that of serum 1
• Ioxaglate is the only ionic low-osmolar agent 1

Clinical Context and Renal Safety

Current evidence shows no consistent superiority of iso-osmolar over low-osmolar agents for preventing contrast-induced nephropathy (CIN):

• The 2009 ACC/AHA guidelines initially recommended iso-osmolar agents as preferred in chronic kidney disease patients, but subsequent meta-analyses of 16-25 trials involving 2,763-3,260 patients found no significant difference in CIN rates between iodixanol and most low-osmolar agents (RR 0.79-0.80, not significant) 1

• The KDIGO 2012 guidelines recommend using either iso-osmolar or low-osmolar contrast media rather than high-osmolar agents in patients at increased risk of contrast-induced AKI, acknowledging that osmolarity alone does not determine nephrotoxicity 1

• Iodixanol showed benefit only when compared to specific agents: ioxaglate (RR 0.58) and iohexol (RR 0.19-0.38), but not against iopamidol, iopromide, or ioversol 1

Important clinical nuances:

• A 2014 network meta-analysis found iodixanol, iomeprol, iopamidol, and ioversol had similarly low CIN rates (5.7-6.1%), while iohexol and ioxaglate had approximately double the risk (11.0-11.2%) 4

• When prophylactic N-acetylcysteine plus hydration is used, nephrotoxicity rates are equivalent between iso-osmolar iodixanol (2.7%) and low-osmolar iobitridol (3.5%) 5

• The American College of Cardiology emphasizes that CIN risk cannot be attributed to osmolarity alone, but ionicity and other agent-specific characteristics also play a role 6

Practical Considerations

Cost-effectiveness concerns:

• Iso-osmolar contrast media cost significantly more than low-osmolar agents (Can $328 vs $128 per 100 mL in Canada) 1
• The Canadian Society of Nephrology recommends selective use of iso-osmolar agents only for patients at high risk of CIN complications, given lack of consistent benefit and resource constraints 1

Patient comfort advantage:

• Iodixanol causes significantly less injection-associated discomfort than low-osmolar agents (17% vs 52% moderate-to-severe discomfort with iohexol) 2, 3
• This represents a consistent advantage across multiple studies 2