Implication for health policy/practice/research/medical education:
Radiotherapy with or without chemotherapy for pelvic malignancies such as gastrointestinal cancers, gynecologic cancers, lymphomas, and sarcomas of the upper abdomen and during total body irradiation may result in radiation-induced kidney injury. The incidence of clinical radiation nephropathy has increased with the use of total-body irradiation in preparation for bone marrow transplantation. Radiation nephropathy usually manifests as proteinuria, hypertension and impairment in urine concentration. The precise pathogenic mechanisms and/or mediators involved in radiation nephropathy remain under active investigation. However, radiation nephropathy is no longer viewed as inevitable, progressive, and untreatable.
The kidneys are vitally important, responsible for producing erythropoietin to stimulate red blood cell production, filtering waste metabolites and electrolytes from the blood, and modulating blood pressure by fluid/electrolyte balance (1). In pelvis radiation therapy (RT), the pronounced radiosensitivity of renal tissue limits the total radiotherapeutic dose that can be applied safely to treatment volumes that include the kidneys (2).
Radiotherapy with or without chemotherapy for pelvic malignancies such as gastrointestinal cancers, gynecologic cancers, lymphomas, and sarcomas of the upper abdomen and during total body irradiation (TBI) may result in radiation-induced kidney injury, especially radiation nephropathy (RN) (1,3,4). The incidence of clinical RN has increased with the use of TBI in preparation for bone marrow transplantation (BMT) and as a consequence of radionuclide therapies. BMT nephropathy usually develops very slowly, over a period of several years, and manifests as proteinuria, hypertension and impairment in urine concentration (4,5).
It is possible that radiation nephropathy could occur after a nuclear accident or because of nuclear terrorism (6,7). Exposures that would cause this would have to be in the 5 to 10 Gy range. “Doses less than 5 Gy would not materially affect the kidneys, whereas doses greater than 10 Gy would cause rapid gastrointestinal death” (8-10).
In RN, as in normal tissue radiation injury in general, it is not possible to predict which subjects will develop the complication. However, considering the threshold dose, sufficient ionizing radiation injures most or all components of the kidney. Glomerular injury is chronologically first, and involves at least its endothelium and mesangium, with evolution to glomerular scarring due to thrombotic microangiopathy. Expression of tubular injury appears to occur somewhat later, even if it is set in motion at the same time as the glomerular injury. Oxidative injury to the glomeruli, could play a mechanistic role. Denuded tubules could allow interstitial entry to mediators that escape from injured glomeruli. Local mediator expression, such as TGFβ1 or activation of renin-angiotensin system could be key in creating tubulointerstitial scarring. Moreover, there are some rare syndromes of radiation sensitivity such as ataxia telangiectasia, but these are not clinically frequent (4). Management of radiation nephropathy includes attention to control of blood pressure and the use of angiotensin-converting-enzyme inhibitors (ACE inhibitors) or angiotensin (AII) receptor blockers (11,12).
Conclusion
Radiation-induced kidney injury involves complex and dynamic interactions between glomerular, tubular, and interstitial cells. Although the precise pathogenic mechanisms and/or mediators involved in radiation nephropathy remain under active investigation. Radiation nephropathy is no longer viewed as inevitable, progressive, and untreatable.
Author’s contribution
MBG is the single author of the manuscript.
Conflict of interests
The author declared no competing interests.
Ethical considerations
Ethical issues (including plagiarism, data fabrication, double publication) have been completely observed by the author.
Funding/Support
None.
Please cite this paper as: Baradaran-Ghahfarokhi M. Radiation-induced kidney injury. J Renal Inj Prev 2012;1(2):49-50. DOI: 10.12861/jrip.2012.17
References
- 1.Dawson LA, Kavanagh BD, Paulino AC, Das SK, Miften M, Li XA. et al. Radiation-associated kidney injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S108–15. doi: 10.1016/j.ijrobp.2009.02.089. [DOI] [PubMed] [Google Scholar]
- 2.Bolling T, Ernst I, Pape H, Martini C, Rube C, Timmermann B. et al. Dose-volume analysis of radiation nephropathy in children: preliminary report of the risk consortium. Int J Radiat Oncol Biol Phys. 2011;80(3):840–4. doi: 10.1016/j.ijrobp.2010.03.021. [DOI] [PubMed] [Google Scholar]
- 3.Bolling T, Willich N, Ernst I. Late effects of abdominal irradiation in children: a review of the literature. Anticancer Res. 2010;30(1):227–31. [PubMed] [Google Scholar]
- 4.Cohen EP, Robbins ME. Radiation nephropathy. Semin Nephrol. 2003;23(5):486–99. doi: 10.1016/s0270-9295(03)00093-7. [DOI] [PubMed] [Google Scholar]
- 5.Pomeranz HD, Henson JW, Lessell S. Radiation-associated cerebral blindness. Am J Ophthalmol. 1998;126(4):609–11. doi: 10.1016/s0002-9394(98)00132-9. [DOI] [PubMed] [Google Scholar]
- 6.Goethals I, Dierckx R, De Meerleer G, Gemmel F, De Neve W, Van De Wiele C. Nuclear medicine in the prediction and detection of radiation associated normal tissue damage of kidney, brain, bone marrow and salivary glands. Nucl Med Commun. 2003;24(8):845–52. doi: 10.1097/01.mnm.0000084581.51410.46. [DOI] [PubMed] [Google Scholar]
- 7.Ozasa K, Shimizu Y, Suyama A, Kasagi F, Soda M, Grant EJ. et al. Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases. Radiat Res. 2012;177(3):229–43. doi: 10.1667/rr2629.1. [DOI] [PubMed] [Google Scholar]
- 8.Sohn W, Clayman RV, Lee JY, Cohen A, Mucksavage P. Low-dose and standard computed tomography scans yield equivalent stone measurements. Urology. 2013;81(2):231–4. doi: 10.1016/j.urology.2012.09.049. [DOI] [PubMed] [Google Scholar]
- 9.Suit H, Goldberg S, Niemierko A, Ancukiewicz M, Hall E, Goitein M. et al. Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects. Radiat Res. 2007;167(1):12–42. doi: 10.1667/RR0527.1. [DOI] [PubMed] [Google Scholar]
- 10.Shahbazi-Gahrouei D, Mortazavi SM, Nasri H, Baradaran A, Baradaran-Ghahfarokhi M, Baradaran-Ghahfarokhi HR. Mobile phone radiation interferes laboratory immunoenzymometric assays: Example chorionic gonadotropin assays. Pathophysiology. 2012;19(1):43–7. doi: 10.1016/j.pathophys.2012.01.002. [DOI] [PubMed] [Google Scholar]
- 11.Brown NJ, Nakamura S, Ma L, Nakamura I, Donnert E, Freeman M. et al. Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney Int. 2000;58(3):1219–27. doi: 10.1046/j.1523-1755.2000.00277.x. [DOI] [PubMed] [Google Scholar]
- 12.Moulder JE, Fish BL, Cohen EP. ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy. Curr Pharm Des. 2003;9(9):737–49. doi: 10.2174/1381612033455422. [DOI] [PubMed] [Google Scholar]