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Radiation nephropathy in the rhesus monkey: morphometric analysis of glomerular and tubular alterations
L C Stephens1, M E Robbins, D A Johnston
1Department of Veterinary Medicine and Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Purpose:
The morphologic responses of the monkey kidney glomeruli and tubules to fractionated irradiation were assessed.
Methods And Materials:
Both kidneys of adult female rhesus monkeys were irradiated with doses of gamma-rays ranging from 24 Gy in 12 fractions up to 36 Gy in 18 fractions. Serial renal biopsies were taken between 1 and 12 weeks after irradiation. The kidneys were removed at necropsy 16-23 weeks after irradiation. Glomeruli were assessed for the presence of pathologic features, including intercapillary eosinophilic material, ectatic capillaries, thrombi, hemorrhage, adhesions, and sclerosis. The relative proportion of renal cortex occupied by glomeruli, interstitium, or tubules was determined using a Chalkley point grid. Tubules were further scored as being either normal or abnormal in appearance.
Results:
Examination of the renal biopsies revealed that progressive glomerular lesions were evident within 4-12 weeks after irradiation. Tubular changes were mild and focal. Morphometric analysis of whole kidneys removed at necropsy demonstrated that numbers of glomeruli with ectatic capillaries, thrombi, and hemorrhage were significantly different from controls at 16-23 weeks after irradiation by all of the doses in the range of 24 to 36 Gy. A significant (p < 0.05) increase in the relative proportion of renal cortex occupied by glomeruli and interstitium was indicative of tubule loss. Further analysis of these tubular changes revealed a highly significant (p < 0.001) dose-dependent increase in the proportion of abnormal to normal tubules. Thus following a dose of 24 Gy in 12 fractions, the ratio of abnormal: normal tubules was approximately 1:2; after 36 Gy in 18 fractions the ratio was 3:1.
Conclusions:
Glomeruli appeared to be very radiosensitive because after the clinically relevant dose of 24 Gy in 12 fractions essentially all glomeruli were altered in the irradiated kidneys as compared to controls. Thus, efforts aimed at increasing the threshold dose for development of radiation nephropathy should be directed primarily at preventing the glomerular lesions.