In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents.
OBJECTIVE
Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks.


METHODS
After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections - proven in the animal model to be effective - were chosen to prolong the animals' exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen.


RESULTS
No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment.


CONCLUSIONS
NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA.
Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain, United Arab Emirates. rlanger@uaeu.ac.ae
R D
RD
Langer
D E
DE
Lorke
K F
KF
Neidl van Gorkom
G
G
Petroianu
S
S
Azimullah
S M
SM
Nurulain
S
S
Singh
M
M
Fuchsjäger
D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000633:toxicity*; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced* / Q000175:diagnosis*; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D005682:Gadolinium