Renal tubulointerstitial changes after internal irradiation with α-particle-emitting actinium daughters Journal Article
| Authors: | Jaggi, J. S.; Seshan, S. V.; McDevitt, M. R.; LaPerle, K.; Sgouros, G.; Scheinberg, D. A. |
| Article Title: | Renal tubulointerstitial changes after internal irradiation with α-particle-emitting actinium daughters |
| Abstract: | The effect of external γ irradiation on the kidneys is well described. However, the mechanisms of radiation nephropathy as a consequence of targeted radionuclide therapies are poorly understood. The functional and morphologic changes were studied chronologically (from 10 to 40 wk) in mouse kidneys after injection with an actinium-225 (225Ac) nanogenerator, a molecular-sized, antibody-targeted, in vivo generator of α-particle- emitting elements. Renal irradiation from free, radioactive daughters of 225Ac led to time-dependent reduction in renal function manifesting as increase in blood urea nitrogen. The histopathologic changes corresponded with the decline in renal function. Glomerular, tubular, and endothelial cell nuclear pleomorphism and focal tubular cell injury, lysis, and karyorrhexis were observed as early as 10 wk. Progressive thinning of the cortex as a result of widespread tubulolysis, collapsed tubules, glomerular crowding, decrease in glomerular cellularity, interstitial inflammation, and an elevated juxtaglomerular cell count were noted at 20 to 30 wk after treatment. By 35 to 40 wk, regeneration of simplified tubules with tubular atrophy and loss with focal, mild interstitial fibrosis had occurred. A lower juxtaglomerular cell count with focal cytoplasmic vacuolization, suggesting increased degranulation, was also observed in this period. A focal increase in tubular and interstitial cell TGF-β1 expression starting at 20 wk, peaking at 25 wk, and later declining in intensity with mild increase in the extracellular matrix deposition was noticed. These findings suggest that internally delivered α-particle irradiation-induced loss of tubular epithelial cells triggers a chain of adaptive changes that result in progressive renal parenchymal damage accompanied by a loss of renal function. These findings are dissimilar to those seen after gamma or beta irradiation of kidneys. Copyright © 2005 by the American Society of Nephrology. |
| Keywords: | immunohistochemistry; controlled study; protein expression; microscopy; nonhuman; animal cell; mouse; animal; electron microscopy; metabolism; animals; mice; microscopy, electron; transforming growth factor beta; atrophy; in vivo study; pathology; radiation injury; mice, inbred balb c; morphology; radiation exposure; extracellular matrix; kidney; bagg albino mouse; kidney function; dosimetry; cell damage; irradiation; transforming growth factor beta1; gamma irradiation; cytolysis; cell count; fibrosing alveolitis; radioimmunotherapy; injury; cell vacuole; degranulation; radiation injuries, experimental; alpha radiation; alpha particles; actinium; actinium 225; kidney tubule; blood chemistry; glomerulus; tgfb1 protein, mouse; juxtaglomerular cell; kidney tubule cell |
| Journal Title: | Journal of the American Society of Nephrology |
| Volume: | 16 |
| Issue: | 9 |
| ISSN: | 1046-6673 |
| Publisher: | American Society of Nephrology |
| Date Published: | 2005-09-01 |
| Start Page: | 2677 |
| End Page: | 2689 |
| Language: | English |
| DOI: | 10.1681/asn.2004110945 |
| PUBMED: | 15987754 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 26" - "Export Date: 24 October 2012" - "CODEN: JASNE" - "Source: Scopus" |
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