Late Effects of the Urinary System
Irradiation to the kidney can result in radiation nephritis or nephropathy after a latent period of 3 to 12 months. Doses greater than 20 Gy can result in significant nephropathy. In a report from the German Registry for the Evaluation of Side Effects after Radiation in Childhood and Adolescence (RISK consortium), 126 patients who underwent radiation therapy to parts of the kidneys for various cancers were evaluated. All patients also received potentially nephrotoxic chemotherapy. Whole kidney volumes exposed to greater than 20 Gy (P = .031) or 30 Gy (P = .003) of radiation were associated with a greater risk for mild degrees of nephrotoxicity. The effect of radiation therapy on the kidney has best been examined in survivors of pediatric Wilms tumor. Generally, studies have shown that the risk of renal insufficiency is higher among children receiving higher doses of radiation.[16,17,18] A correlation between functional impairment and the renal radiation dose was reported in a study of 100 children treated for Wilms tumor. The incidence of impaired creatinine clearance was significantly higher for children receiving more than 12 Gy to the remaining kidney, and all cases of overt renal failure occurred after more than 23 Gy. In a cohort of Wilms tumor survivors evaluated 5 years after receiving abdominal radiation, the prevalence of renal insufficiency, as defined by hypertension, was approximately 7%.
Data from the National Wilms Tumor Study Group and the U.S. Renal Data System indicate that the 20-year cumulative incidence of end-stage renal disease (ESRD) in children with unilateral Wilms tumor and Denys-Drash syndrome (DDS) is 74%, 36% for those with WAGR (Wilms tumor, aniridia, genitourinary abnormalities, mental retardation) syndrome, 7% for male patients with genitourinary anomalies and 0.6% for 5,347 patients with none of these conditions. For patients with bilateral Wilms tumors, the incidence of ESRD is 50% for DDS, 90% for WAGR, 25% for genitourinary anomaly, and 12% for patients for all others.[21,22] ESRD in patients with WAGR and genitourinary anomalies tended to occur relatively late, and often during or after adolescence.
Treatment for Wilms tumor without flank or abdominal radiation therapy was not associated with significant nephrotoxicity in a study of 40 Wilms tumor survivors treated in England.
In the setting of hematopoietic cell transplantation, fewer than 15% of children will develop chronic renal insufficiency or hypertension; the risk is related to the nephrotoxic agents used and the cumulative total-body irradiation dose, fractionation scheme, and interfraction interval. More specifically, the radiation-associated risk rises when the total dose exceeds 12 Gy, the individual fraction size is greater than 2 Gy, or the interval-fraction is less than 4 to 6 hours.[23,24,25,26]