Time-course of the hazard of murine nephropathy induced by total-body irradiation

Purpose: We investigated the form of the hazard function for total-body irr adiation (TBI) induced nephropathy in mice during 1.5 years of follow-up. Material and methods: The material was collected from our previously publis hed data. Following single-dose or fractionated irradiation and bone marrow transplantation (BMT) the mice were tested regularly for kidney damage usi ng the CrEDTA residual activity, percentage haematocrit and blood urea nitr ogen endpoints. The hazard rate was studied in the pooled data of 172 mice for all three endpoints, while fractionation sensitivity was estimated from the direct analysis, which was performed using the CrEDTA residual activit y endpoint and the actual follow-up data in individual mice. Results: The hazard rate of kidney damage following TBI and BMT showed a bi phasic pattern that is most evident with the CrEDTA residual activity endpo int, with a reduced risk of renal failure around week 36 after TBI. Assessm ent of kidney function in individual animals showed evidence of recovery fr om radiation damage around week 36 after TBI. An analysis of fractionation sensitivity showed that the first wave was characterized by an alpha/beta r atio of 8.4 Gy (95% CI: 4.0-14.3 Gy), while the alpha/beta ratio for the se cond wave was estimated at 6.1 Gy (95% CI: 3.3-9.8 Gy). Conclusions: The biphasic nature of the hazard function reported here may b e a unique feature of TBI-induced renal damage. Differentiation between the two phases in terms of their alpha/beta ratio was not possible. The biolog ical basis of this observation remains to be clarified. The reported high a lpha/beta ratio of kidney damage in the TBI situation may have important cl inical implications.