Maktuba Mirrakhimova
1* 
, Qaxramon О’rinboyev
2 , Jurabek Saloxiddinov
3 , Ravshan Makhmudov
4 , Umidjon Islamov
5 , Jasur Saidov
6 , Doniyorbek Khasanov
7 , Aziza Mirzaraximova
8 , Akramjon Teshaboyev
9 , Muhtorali Umarkulov
10 1 Department of Children’s Diseases, Pediatrics, Tashkent State Medical University, Tashkent, Uzbekistan
2 Department of Transplantology, National Medical Center, Tashkent, Uzbekistan
3 Department of Surgical Diseases №1 and Transplantology, Samarkand State Medical University, Samarkand, Uzbekistan
4 Candidate of Medical Sciences, Department of Therapy, Bukhara State Medical Institute Named After Abu Ali ibn Sino, Bukhara, Uzbekistan
5 Department of Surgical Dentistry, Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
6 Department of Medicine, Termez University of Economics and Service, Termez, Uzbekistan
7 Department of Oncology, Andijan State Medical Institute, Andijan, Uzbekistan
8 Department of Economics in the ICT Sector, Tashkent University of Information Technologies named after Muhammad al Khwarizmi, Tashkent, Uzbekistan
9 Department of Social and Humanitarian Sciences, Pedagogy and Psychology, Andijan State Institute of Foreign Languages, Andijan, Uzbekistan
10 Department of Pediatrics of the Fergana Medical Institute of Public Health, Fergana, Uzbekistan
Abstract
Radiation-induced kidney injury embodies a convergent process in which endothelial dysfunction initiates and perpetuates tubulointerstitial fibrosis through oxidative stress, inflammatory cell recruitment, microvascular collapse, and disturbed cellular plasticity. The sequence begins with endothelial apoptosis and barrier breakdown, evolves through chronic hypoxia and fibrosis-promoting signaling, and culminates in irreversible architectural remodeling that compromises renal filtration and oxygen delivery. The hallmark mechanisms include reactive oxygen species-mediated eNOS uncoupling, sustained nuclear factor-kappa B (NF-κB) and transforming growth factor-beta (TGF-β) activation, endothelial-to-mesenchymal (EndMT) and epithelial-to-mesenchymal (EMT) transitions, microvascular rarefaction, and senescent secretory phenotypes – all contributing to a feed-forward loop that defines radiation nephropathy as a progressive, self-amplifying vascular-fibrotic syndrome.
Implication for health policy/practice/research/medical education:
Radiation-induced kidney injury, known as radiation nephropathy, is a progressive vascular-fibrotic syndrome. It starts with endothelial dysfunction, leading to tubulointerstitial fibrosis. This process involves a sequence of events beginning with endothelial cell death and barrier disruption. The injury progresses through chronic hypoxia and signaling that promotes fibrosis, eventually resulting in irreversible structural changes in the kidney. These changes impair the organ’s ability to filter blood and deliver oxygen effectively. Key mechanisms driving this injury include oxidative stress from reactive oxygen species-mediated eNOS uncoupling, persistent activation of inflammatory and fibrotic pathways, endothelial-to-mesenchymal (EndMT) and epithelial-to-mesenchymal (EMT) transitions, and the loss of small blood vessels. These factors create a self-amplifying cycle, worsening the condition over time.
Please cite this paper as: Mirrakhimova M, О’rinboyev Q, Saloxiddinov J, Makhmudov R, Islamov U, Saidov J, Khasanov D, Mirzaraximova A, Akramjon T, Umarkulov M. Mechanisms of endothelial dysfunction and tubulointerstitial fibrosis in radiation-induced kidney injury. J Renal Inj Prev. 2026; 15(3): e38761. doi: 10.34172/jrip.38761.