CAPILLARY ENDOTHELIUM - TARGET SITE OF RENAL RADIATION-INJURY

BACKGROUND: Therapeutic abdominal irradiation may be accompanied by la te occurring progressive renal disease associated with glomerular mesa ngial sclerosis and tubular degeneration. Pathogenesis of this lesion is disputed. EXPERIMENTAL DESIGN: Kidneys of mature pigs were irradiat ed with a single dose of 9.8 Gy Co-60 gamma-rays; serial individual ki dney glomerular filtration rate and renal biopsies were obtained at 3- 4-week intervals with death 24 weeks after irradiation. RESULTS: Irrad iated pigs displayed a progressive reduction in glomerular filtration rate with minimal values observed 12 weeks postirradiation. Morphologi c changes in irradiated glomeruli were characterized by leukocytic att achment to capillary endothelial cells 3-6 weeks after irradiation fol lowed by activation and swelling of endothelial cells and occasional m icrothrombi formation. Similar changes were noted focally in peritubul ar capillaries with accompanying tubular degeneration and atrophy. In glomeruli these endothelial cell changes were followed by increased ca pillary permeability and fluid, erythrocyte, platelet, and leukocytic exudation into the subendothelial/mesangial space resulting in compres sion of glomerular capillary lumina. By 12 weeks postirradiation mesan gial cells showed evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis with continued reduc tion of glomerular filtration rate. CONCLUSIONS: It is concluded that endothelial cell injury represents the primary site of radiation damag e in the kidney and that the progressive glomerular mesangial sclerosi s and reduced renal function of radiation nephropathy may be associate d with exposure of capillary elements to various vasoactive and growth promoting factors that stimulate mesangial contraction and proliferat ion resulting in reduced glomerular filtration area and glomerular fil tration rate.