Preclinical evaluation of erythropoietin administration in a model of radiation-induced kidney dysfunction.
OBJECTIVE
To test whether the clinically available growth factor erythropoietin (EPO) influences radiation-induced normal-tissue damage in a model of kidney dysfunction.


METHODS
Animal experiments were conducted to test the role of EPO administration in a C3H mouse model of unilateral kidney irradiation with 6, 8, and 10 Gy and to assess the effects of 2 different dose levels of EPO. The kidney function was assessed before radiotherapy, as well as 19, 25, 31, and 37 weeks thereafter by means of (99m)Tc-dimercaptosuccinat scans (static scintigraphy).


RESULTS
Concomitant EPO administration significantly increased the degree of radiation-induced kidney dysfunction. A dose of 2,000 IU/kg body weight per injection tended to cause more damage than the lower dose of 500 IU/kg.


CONCLUSIONS
Administration of growth factors concomitant to radiotherapy might modify the development of kidney dysfunction. Although insulin-like growth factor-1 has previously been shown to protect the kidney, such an effect could not be demonstrated for EPO. The latter agent even increased the development of nephropathy.
Andratschke
Nicolaus
N
Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Schnaiter
Andrea
A
Schnaitera
Andrea
A
Weber
Wolfgang A
WA
Cai
Lu
L
Caia
Lu
L
Schill
Sabine
S
Wiedenmann
Nicole
N
Schwaiger
Markus
M
Molls
Michael
M
Nieder
Carsten
C
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D013997:Time Factors
D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D004921:Erythropoietin; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D000068817:Epoetin Alfa