LATE RENAL DAMAGE AFTER TOTAL-BODY IRRADIATION AND BONE-MARROW TRANSPLANTATION IN A MOUSE MODEL - EFFECT OF RADIATION FRACTIONATION

In response to the accumulating evidence that renal damage is now beco ming an important late complication after total body irradiation (TBI) and bone marrow transplantation (BMT), we have tested the effect of f ractionated and hyperfractionated TBI on late kidney damage in a mouse model. TBI was given as fractionated (three fractions in 3 days, Fx 3 ), or hyperfractionated (nine fractions in 3 days, Fx 9) treatment. Ki dney damage was evaluated using [Cr-51]EDTA residual activity, blood u rea nitrogen (BUN) and percentage haematocrit (%Hct) as end-points. We were able to detect progressive renal damage with no evidence of reco very or plateau in the Fx 3 and Fx 9 schedules. The time latency befor e the expression of renal damage was dependent on both total dose and end-point and it was shorter the higher the dose. [Cr-51]EDTA detected renal damage at the same doses as BUN but earlier in time whereas %Hc t detected renal damage at doses lower than both BUN and [Cr-51]EDTA. Reducing the dose per fraction spared the kidney from TBI damage. The dose-response curves for renal damage (using the [Cr-51]EDTA end-point ) were steep, and tended to shift towards lower doses with longer foll ow-up times. The dose-modifying factors defined as the dose needed to cause renal damage in 50% of the animals (ED(50)) using single fractio n TBI divided by the ED(50) using fractionated TBI were 1.3 and 1.9 fo r the Fx 3 and Fx 9, respectively. These results may indicate that pat ients treated with TBI and BMT should be assessed for late kidney dama ge and that fractionation and particularly hyperfractionation may prot ect the kidneys from TBI-induced renal damage.