Contrast-induced nephropathy is a serious complication of intravascular x-ray contrast agents. The osmolality of the contrast medium is an important fact in contrast-induced nephropathy and should ideally be iso-osmolar to blood. Today, nonionic contrast agents are state of the art for vascular use, the ionic contrast agents caused more adverse reactions.
Signs of contrast-induced nephropathy after the application of vascular contrast agents are a serum creatinine increase of 0.5 mg/dL (In the United States, creatinine is typically reported in mg/dL, while in Canada and Europe µmol/L may be used. 1 mg/dL of creatinine is 88.4 µmol/L) or an increase of serum creatinine greater than 25%.

A higher risk of contrast-induced nephropathy is associated with:
The use of a nonionic contrast agent, iso-osmolar to blood and a low dose reduces the risk for contrast-induced nephropathy.

The first-generation contrast agents were all ionic monomers, consisting of a tri-iodinated benzene ring with 2 organic side chains and a carboxyl group. Diatrizoate or iothalamate are common iodinated anions, conjugated with a cation, sodium or meglumine. The ionization at the carboxyl-cation bond makes the agent water soluble.
Ionic monomers have the highest osmolality (high-osmolar contrast media (HOCM) possess an osmolality seven to eight times higher than plasma) of the different groups of contrast agents (CM ratio=1.5) and the lowest viscosity. The osmolality in solutions of ionic monomers ranges from 600 to 2100 mOsm/kg (human plasma = 290 mOsm/kg). These high osmolality is related to some of the adverse reactions. HOCM's have been widely replaced by newer contrast agents with improved tolerability and safety profiles.
Examples of HOCM's are Renografin®-60, Hypaque 76, Hypaque Meglumine, Hypaque Sodium and Conray®.

See also Ionic Contrast Agents.

Osmolality is the number of moles of osmotically active particles (molecules) present in solution per kilogram of water.
High osmolality of contrast agents is related to some of the adverse reactions.

Osmolality of iodinated contrast media:

Adverse reactions on contrast agents are rare, but like all other pharmaceuticals, contrast media are not completely without side effects.
Adverse effects to contrast media include allergic symptoms, anaphylactoid reactions, chemotoxic reactions, idiosyncratic reactions, contrast-induced nephropathy, iodide-induced hyperthyroidism and local tissue damage. An adverse reaction can be related to dose, the toxicity, and the physio-chemical properties of the contrast agent, for example osmolality, viscosity, and hydrophilicity.
Side effects such as a metallic taste in the mouth, generalized warmth or flushing, nausea and vomiting, increase with rapid flow and large volume of the injected agent. Although venous tolerance is usually good, there have been reports of sensation like burning, stinging or numbness and of venospasm.

Characterization of adverse reactions include:

Iodinated contrast media contain small amounts of free iodide. Too much free iodide in the blood may cause hyperthyroidism in patients at risk, but contrast medium induced thyrotoxicosis is rare. The free iodide may also interfere with nuclear medicine diagnostic tests and treatment. However, iodinated contrast agents do not affect thyroid function tests (e.g., T3, T4, TSH) in patients with a normal thyroid.
Guidelines were prepared by the 'Contrast Media Safety Committee of the European Society of Urogenital Radiology' and discussed on the Tenth European Symposium on Urogenital Radiology in September 2003.
Tests of thyroid function before the injection of contrast agents may only be indicated in areas with dietary iodine deficiency. Patients with Graves' disease, multinodular goiter with thyroid autonomy, especially elderly and patients who lives in areas of iodine deficiency are at risk to develop thyrotoxicosis after IV contrast medium and should be monitored by endocrinologists after contrast enhanced CT exams. Prophylaxis may offer some protection in selected high-risk individuals but is not generally recommended.
The free iodide of iodinated contrast agents interferes with thyroidal iodide uptake and impedes diagnostic thyroid scintigraphy and radio-iodine treatment of thyroid malignancies for 2 months after administration.