Radyasyon Nefriti
Özet
İyonize radyasyona bağlı böbrek hasarı ve fonksiyon kaybı olarak tanımlanan radyasyon nefropatisi, özellikle tüm vücut ışınlaması (TVI) ve üst batın radyoterapisi sonrasında gelişen önemli bir deterministik yan etkidir. Klinik olarak maruz kalınan doza ve böbrek hacmine bağlı olarak ortaya çıkan bu tablo, latent bir dönemin ardından azotemi, malign hipertansiyon, anemi ve proteinüri ile kendini göstermektedir. Patofizyolojik süreçte; kapiller endotel hasarı, mezanjioliz, tübüler hücre lizizi ve belirgin tübulointerstisyel fibrozis gibi glomerüler, vasküler ve tübüler seviyelerde morfolojik değişiklikler eş zamanlı olarak izlenmektedir. Teşhis aşamasında split böbrek fonksiyonlarının takibi amacıyla tedavi öncesi ve sonrasında böbrek sintigrafisinden yararlanılması, hasarın erken tespiti ve fonksiyonel kaybın derecelendirilmesi açısından kritik önem taşır. Radyasyon nefrotoksisitesini önlemede ve azaltmada yoğunluk ayarlı radyoterapi (YART) gibi güncel onkolojik teknolojilerin kullanımı, kritik böbrek parankiminin korunmasını sağlayan doz-hacim kısıtlamalarına uyulması ve anjiyotensin dönüştürücü enzim (ACE) inhibitörlerinin (özellikle kaptopril) tedavi sürecine dahil edilmesi başarılı klinik stratejiler arasında yer almaktadır. Hematopoetik kök hücre nakli gibi süreçlerin ardından son dönem böbrek hastalığı gelişen vakalarda prognozun kötü olması, radyosensitif bir organ olan böbreğin korunmasına yönelik koruyucu yaklaşımların ve multidisipliner takibin önemini açıkça ortaya koymaktadır.
Radiation nephropathy, defined as kidney damage and loss of function due to ionizing radiation, is a significant deterministic side effect that develops particularly after total body irradiation (TBI) and upper abdominal radiotherapy. This clinical condition, which depends on the radiation dose and exposed kidney volume, manifests after a latent period with symptoms such as azotemia, malignant hypertension, anemia, and proteinuria. In the pathophysiological process, morphological changes including capillary endothelial damage, mesangiolysis, tubular cell lysis, and prominent tubulointerstitial fibrosis are observed simultaneously at glomerular, vascular, and tubular levels. For diagnosis and monitoring of split kidney function, utilizing renal scintigraphy before and after treatment is critical for early detection of injury and grading functional loss. In preventing and mitigating radiation nephrotoxicity, using advanced oncological technologies like intensity-modulated radiotherapy (IMRT), adhering to dose-volume constraints that protect critical renal parenchyma, and incorporating angiotensin-converting enzyme (ACE) inhibitors (especially captopril) into the treatment regimen constitute successful clinical strategies. The poor prognosis of patients who develop end-stage renal disease following processes like hematopoietic stem cell transplantation highlights the vital importance of protective approaches and multidisciplinary management for this radiosensitive organ.
Referanslar
Kamiya K, Ozasa K, Akiba S, et al. Long-term effects of radiation exposure on health. Lancet. 2015; 386(9992): 469–478.
Citrin DE, Prasanna PGS, Walker AJ, et al. Radiationinduced fibrosis: mechanisms and opportunities to mitigate: report of an NCI workshop, September 19, 2016. Radiat Res. 2017; 188(1): 1–20.
Cohen EP and Robbins ME. Radiation nephropathy. Semin Nephrol 2003; 23(5): 486–499.
Kunkler PB, Farr RF and Luxton RW. The limit of renal tolerance to X-rays: an investigation into renal damage occurring following the treatment of tumours of the testis by abdominal baths. Br J Radiol. 1952; 25(292): 192–201.
Wong JYC, Filippi AR, Dabaja BS, et al. Total body irradiation: guidelines from the International Lymphoma Radiation Oncology Group (ILROG). Int J Radiat Oncol Biol Phys. 2018; 101(3): 521–529.
Dawson LA, Kavanagh BD, Paulino AC, et al. Radiationassociated kidney injury. Int J Radiat Oncol Biol Phys 2010; 76(3 Suppl): S108–S115.
Luxton RW. Radiation nephritis. Q J Med 1953; 22(86):215–242.
Cheng JC, Schultheiss TE and Wong JY. Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation. Int J Radiat Oncol Biol Phys 2008; 71(5): 1436–1443.
Keane WF, Crosson JT, Staley NA, et al. Radiation-induced renal disease. A Clinicopathologic study Am J Med 1976; 60(1): 127–137.
Imig JD, HyeKhan MA, Sharma A, et al. Radiation-induced afferent arteriolar endothelial-dependent dysfunction involves decreased epoxygenase metabolites. Am J Physiol Heart Circ Physiol 2016; 310(11): H1695–H1701.
Ahmad A, Mitrofanova A, Bielawski J, et al. Sphingomyelinase-like phosphodiesterase 3b mediates radiation- induced damage of renal podocytes. Faseb J 2017; 31(2): 771–780.
Shapiro AP, Cavallo T, Cooper W, et al. Hypertension in radiation nephritis: report of a patient with unilateral disease, elevated renin activity levels, and reversal after unilateral nephrectomy. Arch Intern Med 1977; 137(7): 848–851.
Glezerman IG, Jhaveri KD, Watson TH, et al. Chronic kidney disease, thrombotic microangiopathy, and hypertension following T cell-depleted hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2010; 16(7): 976–984.
Tseng J, Citrin DE, Waldman M, et al. Thrombotic microangiopathy in metastatic melanoma patients treated with adoptive cell therapy and total body irradiation. Cancer 2014; 120(9): 1426–1432.
May KS, Yang GY, Khushalani NI, et al. Association of technetium(99m) MAG-3 renal scintigraphy with change in creatinine clearance following chemoradiation to the abdomen in patients with gastrointestinal malignancies. J Gastrointest Oncol 2010; 1(1): 7–15.
Jackson P, Foroudi F, Pham D, et al. Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT. Radiat Oncol 2014; 9: 253.
Skinner HD and Krishnan S. Predicting, preventing, treating and understanding radiation nephropathy. J Gastrointest Oncol 2010; 1(1): 2–4.
Moulder JE, Fish BL and Cohen EP. ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy. Curr Pharm Des 2003; 9(9): 737–749.
Moulder JE, Fish BL and Cohen EP. Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy. Bone Marrow Transplant 1997; 19(7): 729–735.
Cohen EP, Irving AA, Drobyski WR, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. Int J Radiat Oncol Biol Phys 2008; 70(5): 1546–1551.
Moulder JE, Cohen EP and Fish BL. Captopril and losartan for mitigation of renal injury caused by single dose total-body irradiation. Radiat Res 2011; 175(1):29–36.
Medhora M, Gao F, Wu Q, et al. Model development and use of ACE inhibitors for preclinical mitigation of radiationinduced injury to multiple organs. Radiat Res 2014; 182(5):545–555.
Cohen EP, Piering WF, Kabler-Babbitt C, et al. End-stage renal disease (ESRD) after bone marrow transplantation: poor survival compared to other causes of ESRD. Nephron 1998; 79(4): 408–412.
