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Radiation Nephropathy in a Nonhuman Primate Model of Partial-Body Irradiation With Minimal Bone Marrow Sparing—Part 2

Histopathology, Mediators, and Mechanisms

Parker, George A.1; Cohen, Eric P.2; Li, Na1; Takayama, Kyle1; Farese, Ann M.3; MacVittie, Thomas J.3

doi: 10.1097/HP.0000000000000935
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Male rhesus macaques were subjected to partial-body irradiation at 10, 11, or 12 Gy with 5% bone marrow protection. Animals were euthanized when dictated by prospectively determined clinical parameters or at approximately 180 d following irradiation. Histological sections of kidney were stained with hematoxylin and eosin as well as a battery of histochemical and immunohistochemical stains. Histopathological alterations were centered on glomerular changes and fibrosis of glomeruli and the interstitial compartment. These changes were first noted in animals necropsied approximately 100 d postirradiation and continued in animals necropsied through the observation period. Glomerular changes included congestion, thrombosis, erythrocyte degeneration, capillary tuft dilation, fibrin deposition, altered quantity and dispersion pattern of von Willebrand factor, increased mesangial matrix, and mesangial deposits of material that stained positively with periodic acid-Schiff staining. Areas of interstitial and glomerular fibrosis, as demonstrated by Masson’s trichrome staining, were topographically associated with increased immunohistochemical staining for connective tissue growth factor, alpha smooth muscle actin, and collagen 1, but there was little staining for transforming growth factor beta. Fibrotic glomeruli had reduced microvascularity as demonstrated by reduced CD31 immunohistochemical staining. Vascular congestion was commonly noted in the region of the corticomedullary junction, and proteinaceous casts were commonly noted in cortical and medullary tubules. Longitudinal analysis of histopathological alterations provided evidence defining the latency, severity, and progression of delayed radiation-induced kidney injury.

1Charles River Laboratories/Pathology Associates, Durham, NC;

2 University of Maryland, School of Medicine, Nephrology Division, Baltimore, MD;

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

The authors declare no conflicts of interest.

For correspondence contact George A. Parker, Charles River Laboratories/Pathology Associates, 4025 Stirrup Creek Drive, Suite 150, Durham, NC 27703, or email at george.parker@crl.com.

(Manuscript accepted 21 June 2019)

© 2019 by the Health Physics Society