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.
Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Nicolaus
N
Andratschke
Andrea
A
Schnaiter
Andrea
A
Schnaitera
Wolfgang A
WA
Weber
Lu
L
Cai
Lu
L
Caia
Sabine
S
Schill
Nicole
N
Wiedenmann
Markus
M
Schwaiger
Michael
M
Molls
Carsten
C
Nieder
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