Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: in vitro study.
OBJECTIVE
To test in vitro whether gadolinium-based contrast agents induce fewer toxic effects on renal tubular cells than does an iodinated contrast medium at concentrations used for angiography.


METHODS
LLC-PK1 cells were incubated with iomeprol, gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, gadodiamide, and corresponding mannitol solutions for 24 hours at 37 degrees C in two experimental settings: measurements with equally attenuating solutions and measurements with equimolar solutions. Cytotoxicity was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, trypan blue testing, and an assay to detect apoptosis and necrosis. Data were analyzed with analyses of variance and post hoc tests.


RESULTS
Yielding the same x-ray attenuation, iomeprol-300 and iomeprol-150 at concentrations of 2.34-18.75 mg of iodine per milliliter induced significantly (P < .001) lower inhibition of MTT conversion (74%-102% of undamaged control cells) compared with 15.63-125.00 mmol/L concentrations of the gadolinium-based agents (mean percentages of undamaged control cells: 48%-80%, 50%-87%, 60%-95%, and 56%-92% with gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, and gadodiamide, respectively). At equimolar concentrations (62.5 mmol/L), iomeprol-190 induced a mean extent of inhibition of MTT conversion (69% of undamaged control cells) similar to that induced by gadoterate meglumine (71%) and gadodiamide (70%), whereas gadopentetate dimeglumine and gadobenate dimeglumine induced stronger effects (63% and 64%, respectively; P < .001). At trypan blue testing, there were more dead cells after incubation with 125 mmol/L gadopentetate dimeglumine than after incubation with iomeprol-190 (57% vs 19%, P < .001). The 125 mmol/L gadopentetate and gadobenate formulations induced more necrosis and apoptosis than did gadoterate meglumine, gadodiamide, and iomeprol (mean percentage difference between treated and untreated control cells: for necrosis, +124%, +95%, +17%, -6%, and +3%, respectively; for apoptosis, +34%, +35%, +13%, +4%, and +5%, respectively; P < .001).


CONCLUSIONS
At angiographic concentrations, gadolinium-based contrast agents do not induce fewer cytotoxic effects on cultured renal tubular cells than does iomeprol.
Heinrich
Marc C
MC
Institute of Diagnostic Radiology, University Hospital of Erlangen, Maximiliansplatz 1, 91054 Erlangen, Germany. Dr.MarcHeinrich@gmx.de
Kuhlmann
Martin K
MK
Kohlbacher
Sonja
S
Scheer
Mario
M
Grgic
Aleksandar
A
Heckmann
Martina B
MB
Uder
Michael
M
D000792:Angiography; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004396:Coloring Agents; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D005682:Gadolinium / Q000008:administration & dosage / Q000633:toxicity*; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000633:toxicity; D007455:Iodine / Q000008:administration & dosage / Q000633:toxicity*; D007479:Iopamidol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D018374:LLC-PK1 Cells; D008353:Mannitol / Q000633:toxicity; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D009336:Necrosis; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity; D013552:Swine; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
D004396:Coloring Agents; D003287:Contrast Media; D009942:Organometallic Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C064572:gadobenic acid; C057937:iomeprol; D008353:Mannitol; D008536:Meglumine; C064925:gadodiamide; D007455:Iodine; D005682:Gadolinium; C022616:thiazolyl blue; D014343:Trypan Blue; D007479:Iopamidol; D019786:Gadolinium DTPA; C072417:gadoterate meglumine