Renal damage after total body irradiation in a mouse model for bone marrow transplantation: effect of radiation dose rate

Late renal damage after total body irradiation (TBI) and bone marrow transplantation (BMT) is a recently recognised morbidity. We have tested the effect of single fraction TBI given at two different dose rates on late kidney damage in a mouse model. TBI was given at either high dose rate (HDR; 0.71 Gy/min) or low dose rate (LDR; 0.08 Gy/min). Transplantation with syngeneic marrow cells was done 4-6 h after TBI. Kidney damage was tested using 51CrEDTA residual activity, blood urea nitrogen (BUN) and percentage haematocrit (Hct). TBI alone given at HDR or LDR caused progressive renal damage with no evidence of recovery or plateau. The time latency before the expression of damage was dependent on both dose and the end point used. It was shorter the higher the dose. 51CrEDTA detected renal damage at the same doses as BUN but earlier in time, while %Hct showed evidence of renal damage at doses lower than both BUN and 51CrEDTA. Using the 51CrEDTA the dose-response curves for renal damage were steep and continuously shifting towards lower doses as follow-up time after treatment increased. There was a sparing effect of reducing the dose rate that was more evident at follow-up times of less than a year than at 66 weeks after TBI. Thus, the dose modifying ratio (DMF), defined as the dose needed to cause renal damage in 50% of irradiated animals (ED50) using LDR divided by the ED50 using HDR, was dependent on the time of evaluation. It varied from 1.2 (week 18) to 1 (week 66). Clinically, this study may indicate that patients treated with TBI and BMT should continuously be assessed for late kidney damage. The use of sensitive techniques using radionuclides to measure renal damage is recommended