Radiation-induced kidney toxicity: molecular and cellular pathogenesis.
Radiation nephropathy (RN) is a kidney injury induced by ionizing radiation. In a clinical setting, ionizing radiation is used in radiotherapy (RT). The use and the intensity of radiation therapy is limited by normal-tissue damage including kidney toxicity. Different thresholds for kidney toxicity exist for different entities of RT. Histopathologic features of RN include vascular, glomerular and tubulointerstitial damage. The different molecular and cellular pathomechanisms involved in RN are not fully understood. Ionizing radiation causes double-stranded breaks in the DNA, followed by cell death including apoptosis and necrosis of renal endothelial, tubular and glomerular cells. Especially in the latent phase of RN oxidative stress and inflammation have been proposed as putative pathomechanisms, but so far no clear evidence was found. Cellular senescence, activation of the renin-angiotensin-aldosterone-system and vascular dysfunction might contribute to RN, but only limited data is available. Several signalling pathways have been identified in animal models of RN and different approaches to mitigate RN have been investigated. Drugs that attenuate cell death and inflammation or reduce oxidative stress and renal fibrosis were tested. Renin-angiotensin-aldosterone-system blockade, anti-apoptotic drugs, statins, and antioxidants have been shown to reduce the severity of RN. These results provide a rationale for the development of new strategies to prevent or reduce radiation-induced kidney toxicity.
['Klaus|Richard|R|', 'Niyazi|Maximilian|M|', 'Lange-Sperandio|Bärbel|B|http://orcid.org/0000-0001-8898-3459']
D000818:Animals D016922:Cellular Senescence D004249:DNA Damage D005355:Fibrosis D006801:Humans D006978:Hypertension, Renovascular D007249:Inflammation D007668:Kidney D018384:Oxidative Stress D011832:Radiation Injuries D011878:Radiotherapy D012084:Renin-Angiotensin System
Radiation nephropathy Radiotherapy Cellular senescence Renal fibrosis DNA damage Renal inflammation Total body irradiation