History
Previous exposure to a sufficient dose of ionizing radiation is a necessary element in the patient's history. External-beam irradiation is usually a clear-cut feature in the history, and it should have encompassed the kidney areas. Use of a radioactive isotope in therapeutic doses may not be obvious.
Classically, exposure of the kidneys to x-rays or gamma rays in a dose higher than 2000 cGy (rads) is required to cause radiation nephropathy. However, a 10-Gy single-fraction dose is sufficient to cause chronic kidney disease after bone marrow transplantation (BMT), [16] and with many years of follow-up, a 1-Gy single-fraction dose is associated with development of chronic kidney disease. [5] While these effects are not immediate, as is the case for radiation injury to the bone marrow or gastrointestinal (GI) tract, kidney injury at these doses indicates that the kidneys are quite radiosensitive.
Modern radiation therapy (RT) is sharply focused on the area to be treated; therefore, RT for uterine cervical cancer or for prostate cancer is very unlikely to result in irradiation of the kidneys. The risk of RT-induced kidney injury depends on the radiation dose and whether the partial or whole volume of one or both kidneys is exposed. Most radiation oncologists use the dose-volume histogram information to assess the organs at risk of radiation-induced injury. [17]
In patients who have undergone BMT, a history of total-body irradiation (TBI) for pre-BMT conditioning should be determined. Partial renal shielding reduces, but does not eliminate, the risk of BMT nephropathy. Retrospective evaluation of patients receiving T-cell depletion hematopoietic stem cell transplantation showed that the use of TBI predisposed patients to hypertension and chronic kidney disease. [17]
Because radiation nephropathy is a delayed injury, kidney disease that quickly follows kidney irradiation (ie, within hours or days) is usually caused by some other factor. Classic acute radiation nephropathy occurs 6-12 months after irradiation, and chronic radiation nephropathy may not develop for years. Similarly, proteinuria or hypertension ascribed to radiation nephropathy does not develop for months or years.
Expected symptoms of radiation nephropathy and BMT nephropathy are the same as those observed in patients with chronic kidney disease. Nocturia may develop due to the loss of urine-concentrating ability. Retention of salt and water may lead to edema and an increase in blood pressure. Anemia may occur, with fatigue, dyspnea, and loss of endurance. Loss of appetite, nausea, and weight loss may occur when there is a severe reduction in renal function. Itching may occur with advanced renal failure—that is, stage V chronic kidney disease (see Staging).
Physical Examination
Hypertension, often severe, is a major feature of radiation nephropathy. It may be the only clinical feature. When this blood pressure elevation is associated with end-organ damage, such as eyeground changes or encephalopathy, it is termed malignant. Malignant hypertension has been reported in radiation nephropathy. Eyeground abnormalities, such as cotton-wool spots, retinal hemorrhage, and even optic disc edema, may occur at lower levels of blood pressure elevation than would ordinarily cause such changes. [18]
Long-standing hypertension may result in left ventricular enlargement or hypertrophy, which may be detectable on examination. Findings on physical examination are not specific for radiation nephropathy or BMT nephropathy.
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Evolution of the glomerular filtration rate (GFR) versus time in a case of nephropathy related to bone marrow transplantation (BMT). GFR may be approximated as 100/plasma creatinine on the Y axis and graphed versus time on the X axis. As is true in many cases of BMT nephropathy, the evolution appears to be biphasic, with an initial rapid decline in GFR, then a slower plateau phase. The patient whose data are shown here ultimately underwent kidney transplantation.
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Photomicrograph of a kidney-biopsy sample in a case of nephropathy associated with bone marrow transplantation (periodic acid-Schiff stain). A glomerulus is in the center and is relatively hypocellular. Increased mesangial matrix is present. The glomerular basement membranes are not thickened; in some places, however, they are separated from the capillary lumens by a low-density, matrixlike material. Interstitial fibrosis separates the tubules from each other. Arteriolar thickening and arteriolar hyalin are present.
