Early detection of radiation-induced glomerular injury by albumin permeability assay

Renal irradiation leads predictably to glomerular vascular injury, cell lys is, matrix accumulation, sclerosis and loss of renal function. The immediat e effects of renal irradiation that may be associated with glomerular patho logy and proteinuria are not clear in the human disease or its rat model. W e hypothesized that radiation-induced injury causes immediate and subtle al terations in glomerular physiology independent of the neurohumoral and hemo dynamic regulatory mechanisms. We employed a sensitive iii vitro functional assay of glomerular albumin permeability (P-alb) to demonstrate radiation- induced damage to the glomerular filtration barrier immediately after total -body irradiation of rats. In blinded experiments, control rats were sham-t reated, and experimental rats received 9.5 Gy X rays. Rats were killed huma nely at 1 h to 9 weeks after irradiation and glomeruli were isolated. In pa rallel experiments, glomeruli were isolated from normal rats and irradiated in vitro. The change in glomerular capillary permeability due to an experi mental oncotic gradient was determined using videomicroscopy and P-alb was calculated. Results show that in vivo or kt vitro irradiation of glomeruli caused an increased P-alb at 1 h. Increased P-alb was observed up to 3 week s after irradiation. Glomeruli from mice irradiated with 9.5 or 19.0 Gy X r ays did not show increased P-alb at 1 h postirradiation, We conclude that g lomerular protein permeability of irradiated rats increases in a dose-depen dent manner immediately after irradiation and that it appears to be indepen dent of hemodynamic or systemic influences. (C) 2001 by Radiation Research Society.