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Radiation Nephropathy in a Nonhuman Primate Model of Partial-body Irradiation with Minimal Bone Marrow Sparing—Part 1

Acute and Chronic Kidney Injury and the Influence of Neupogen

Cohen, Eric P.1; Hankey, Kim G.2; Farese, Ann M.2; Parker, George A.3; Jones, Jace W.4; Kane, Maureen A.4; Bennett, Alexander2; MacVittie, Thomas J.2

doi: 10.1097/HP.0000000000000960

Acute and chronic kidney injury may occur after accidental prompt radiation exposures. We have modeled their occurrence in a nonhuman primate model. Subjects who are exposed to more than 5-Gy prompt irradiation are apt to show blood cell cytopenias and be treated with granulocyte colony-stimulating factors such as Neupogen® or Neulasta® to mitigate the hematologic injury of the acute radiation syndrome. Neupogen or Neulasta are now approved by the US Food and Drug Administration for this indication. This will significantly increase the number of survivors of acute radiation exposures who will be at risk for delayed effects of radiation exposure, which includes acute and chronic kidney injury. The primary objectives of the present two companion manuscripts were to assess natural history of delayed radiation-induced renal injury in a nonhuman primate model of acute, high-dose, partial-body irradiation with 5% bone marrow sparing to include the clinical and histopathological evidence and the effect of Neupogen administration on morbidity and mortality. In this study, 88 nonhuman primates underwent 10- or 11-Gy partial-body irradiation with 5% bone marrow sparing, of which 36 were treated with Neupogen within 1, 3, or 5 d postirradiation. All animals were followed up to 180 d after irradiation. Renal function and histology end points showed early acute and later chronic kidney injury. These end points were not affected by use of Neupogen. We conclude that use of Neupogen to mitigate against the hematopoietic acute radiation syndrome has no impact on acute or chronic kidney injury.

1Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD 21201.

2Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, MD 21201.

3Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD.

4Charles River Laboratories, Durham, NC.

For correspondence contact Dr. Eric P. Cohen, Nephrology Division, Department of Medicine, University of Maryland School of Medicine, 22 S. Greene St., Baltimore, MD 21201, or email at

(Manuscript accepted 21 June 2018)

© 2019 by the Health Physics Society