PROGRESSION RATE OF RADIATION-DAMAGE TO THE MOUSE KIDNEY - A QUANTITATIVE-ANALYSIS OF EXPERIMENTAL-DATA USING A SIMPLE MATHEMATICAL-MODEL OF THE NEPHRON
L. Judas et al., PROGRESSION RATE OF RADIATION-DAMAGE TO THE MOUSE KIDNEY - A QUANTITATIVE-ANALYSIS OF EXPERIMENTAL-DATA USING A SIMPLE MATHEMATICAL-MODEL OF THE NEPHRON, International journal of radiation biology, 72(4), 1997, pp. 461-473
Citations number
20
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging","Nuclear Sciences & Tecnology
Mouse kidneys were irradiated bilaterally with a range of single or fr
actionated X-ray doses. After an interval of 2 weeks or 26 weeks, the
animals were reirradiated with a range of single X-ray doses. The rate
of development of functional kidney damage was assessed repeatedly by
the Cr-51-EDTA clearance assay. The rate at which the damage is expre
ssed was found to depend on the primary dose, on the interval between
primary treatment and retreatment, and on the retreatment dose. A subs
et of the data was analysed using a mathematical model of nephron func
tion. In the model, the residual activity of Cr-51-EDTA depends on the
glomerular filtration rate (GFR). The GFR is related to the cellulari
ties of three target cell populations. The filtration capacity of the
glomerulus is assumed to depend on the numbers of glomerular endotheli
al cells and mesangial cells. The reabsorption capacity of the tubule
is related to the number of tubular epithelial cells. The impact of tu
bulo-glomerular feedback and the reserve capacity of the kidney on res
idual activity is considered. The target cell populations are assumed
to be of a flexible type, i.e. to consist of cells which are all both
functional and self-renewing. Free parameters of the model were optimi
zed by minimizing the residual sum of squares. With the optimized para
meter values, the measured and the model-predicted rates of progressio
n of the functional damage correspond well for a wide range of irradia
tion schedules. The model analysis suggests a pronounced role of tubul
o-glomerular feedback in the development of functional injury in the k
idney. It is concluded that the model represents a good starting point
for quantitative studies of the cellular basis of radiation nephropat
hy.