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 t ransplantation (BMT) is a recently recognised morbidity. We have teste d 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 d ose rate (HDR; 0.71 Gy/min) or low dose rate (LDR; 0.08 Gy/min). Trans plantation with syngeneic marrow cells was done 4-6 h after TBI. Kidne y damage was tested using (51)CrEDTA residual activity, blood urea nit rogen (BUN) and percentage haematocrit (Hct). TBI alone given at HDR o r LDR caused progressive renal damage with no evidence of recovery or plateau. The time latency before the expression of damage was dependen t on both dose and the end point used. It was shorter the higher the d ose. (51)CrEDTA. detected renal damage at the same doses as BUN but ea rlier in time, while %Hct showed evidence of renal damage at doses low er than both BUN and (51)CrEDTA, Using the (51)CrEDTA the dose-respons e curves for renal damage were steep and continuously shifting towards lower doses as fellow-up time after treatment increased. There was a sparing effect of reducing the dose rate that was more evident at foll ow-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 (ED(50)) using LDR divided by the ED(50) using HDR, was dependent on the time of evaluation. It varied f rom 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 radionu clides to measure renal damage is recommended.