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

摘要

PURPOSE: We investigated the form of the hazard function for total-body irradiation (TBI) induced nephropathy in mice during 1.5 years of follow-up. MATERIAL AND METHODS: The material was collected from our previously published data. Following single-dose or fractionated irradiation and bone marrow transplantation (BMT) the mice were tested regularly for kidney damage using the CrEDTA residual activity, percentage haematocrit and blood urea nitrogen 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 activity endpoint and the actual follow-up data in individual mice. RESULTS: The hazard rate of kidney damage following TBI and BMT showed a biphasic pattern that is most evident with the CrEDTA residual activity endpoint, with a reduced risk of renal failure around week 36 after TBI. Assessment of kidney function in individual animals showed evidence of recovery from radiation damage around week 36 after TBI. An analysis of fractionation sensitivity showed that the first wave was characterized by an alpha/beta ratio of 8.4Gy (95% CI: 4.0-14.3Gy), while the alpha/beta ratio for the second 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 be a unique feature of TBI-induced renal damage. Differentiation between the two phases in terms of their alpha/beta ratio was not possible. The biological basis of this observation remains to be clarified. The reported high alpha/beta ratio of kidney damage in the TBI situation may have important clinical implications.