Tuesday, July 13, 2010

TOPIC DISCUSSION: Gadolinium and NSF- How to image high risk patients

NSF caught the nephrologist community by surprise with its initial identification in 1997 and had a formal description as a unique entity in 2001. The cause of NSF eluded diagnosis, but it happened only in patients with kidney disease and the culprit was the magnetic resonance contrast enhancing imaging agent. Gadolinium(Gd) has paramagnetic properties that disturb relaxation of water protons and by shortening relaxation it increases signal intensity, making it an excellent contrast agent. For safe use of the contrast-enhancing benefits of Gd, the metal must be sequestered by an organic ligand. In general, there are two major categories of ligand, linear and macrocyclic, are based on biochemical structure. And based on the animal data, linear based agents tend to have significantly higher tissue concentration and hence long term retention in comparison to macrocyclic based agents. Renal clearance of Gd approximates creatinine clearance in normal individuals. and have a terminal half life of 1.3 to 1.6 hours. The terminal half life increases in patients with CKD stage 3 (4-8hrs) and stage 4(18-34hrs). Agents with a component of liver clearance have a terminal half life of 6.1 to 9.5 hrs with stage 3 and 4 CKD respectively.

Gd serum elimination using hemodialysis is approximately 74% with 1 treatment, 92% with 2 treatments and 99% after 3 treatments. PD is relatively ineffective in Gd removal

Who is at Maximum risk? - Notably, no cases in stage 1-3 CKD have been confirmed in the published literature so far. In the HALT-PKD and CRISP studies, patients with ADPKD stages I through 3 CKD underwent 1111 Gd exposures with no occurrence of NSF. A total of 592 patients who had stages 3 through 4 CKD were exposed to Gd also did not develop NSF. 88 patients who had stages 1 through 4 CKD underwent 94 Gd exposures, including 34 patients with stage 4 CKD did not develop NSF. Finally, none of 2053 patients ( Stage 3 44.7%, stage 4 23.9%, stage 5 5.7%) who were exposed to 2278 MRIs developed NSF during 29 months of follow-up. The literature suggests that dialysis dependent patients with ESRD, stage 5 CKD and AKI maintain the highest risk.
Imaging with Gadolinium of high risk patients. On the basis of current knowledge, the following statements on patient risk for NSF can be made:
1. Use only macrocyclic gadolinium based contrast agents.
2. Use the lowest dosage required to obtain quality images.
3. Avoid IV iron and high dose ESA's before and after anticipated exposure.
4. Patients with stages I through 3 CKD do not seem to maintain risk for NSF after gadolinium exposure.
5. Patients with stage 4 CKD maintain modest risk and the risk increases in the presence of other factors like pro-inflammatory states, metabolic acidosis, hypercalcemia hyperphosphatemia and liver failure. Hence optimize metabolic status before anticipated exposure.
6. Arrange HD for patients with CKD stage 5, AKI and those dependent on dialysis.

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