Iron-mobilizing properties of the gadolinium-DTPA complex: clinical and experimental observations.
BACKGROUND
Gadolinium (Gd) magnetic resonance imaging (MRI) contrast agents are considered to be safe in patients with impaired renal function. Our study investigates a mechanism of severe iron intoxication with life-threatening serum iron levels in a haemodialysis patient following MRI with Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. His previous history was remarkable for multiple blood transfusions and biochemical evidence of iron overload. We hypothesized that Gd-DTPA may have an iron-mobilizing effect in specific conditions of iron overload combined with prolonged exposure to the agent.


METHODS
For the in vitro study, Gd-DTPA was added to mice liver homogenate and iron metabolism parameters were measured after incubation in comparison with the same samples incubated with saline only. For the in vivo study, an experimental model of acute renal failure in iron-overloaded rats was designed. Previously iron-overloaded and normally fed rats underwent bilateral nephrectomy by renal pedicle ligation, followed by Gd-DTPA or saline injection. Iron and iron saturation levels were checked before and 24 h after Gd-DTPA or vehicle administration.


RESULTS
Significant mobilization of iron from mice liver tissue homogenate in mixtures with Gd in vitro was seen in the control (saline) and in the experimental (Gd) groups (513+/-99.1 vs 1117.8+/-360.8 microg/dl, respectively; P<0.05). Administration of Gd-DTPA to iron-overloaded rats after renal pedicle ligation caused marked elevation of serum iron from baseline 143+/-3.4 to 570+/-8 microg/dl (P<0.0001). There were no changes of the named parameter, either in iron-overloaded anuric rats after saline injection or in normal diet uraemic animals, following Gd-DTPA administration.


CONCLUSIONS
The combination of iron overload and lack of adequate clearance of Gd chelates may cause massive liberation of iron with dangerous elevation of free serum iron. It is highly recommended that after Gd contrast study, end-stage renal disease patients with probable iron overload should undergo prompt and intensive haemodialysis for prevention of this serious complication.
Vorobiov
Marina
M
Department of Nephrology, Soroka Medical Center, Ben Gurion University of the Negev, Faculty of Health Sciences, PO Box 151, Beer Sheva 84101, Israel. marinavorobiov@netscape.net
Basok
Anna
A
Tovbin
David
D
Shnaider
Alla
A
Katchko
Leonid
L
Rogachev
Boris
B
D000328:Adult; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects* / Q000633:toxicity; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000009:adverse effects* / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000150:complications; D008279:Magnetic Resonance Imaging / Q000009:adverse effects; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis
D003287:Contrast Media; D007501:Iron; D019786:Gadolinium DTPA