RADIATION RESPONSE OF THE MONKEY KIDNEY FOLLOWING CONTRALATERAL NEPHRECTOMY

Purpose: The long-term functional and morphologic responses of the hyp ertrophied monkey kidney after unilateral nephrectomy to fractionated irradiation were assessed. Methods and Materials: The right kidney of 13 adult female rhesus monkeys was removed. Twelve weeks after unilate ral nephrectomy (UN) the remaining kidney received fractionated doses of gamma-rays ranging from 35.2 Gy/16 fractions (F) up to 44 Gy/20 F. Glomerular filtration rate, effective renal plasma flow, blood urea ni trogen, serum creatinine, and hematocrit values were measured up to 10 7 weeks postirradiation (PI). The monkeys were killed and the remainin g kidneys were removed 107 weeks PI or earlier when end-stage renal fa ilure was exhibited. Glomeruli were scored for the presence/absence of several pathologic features including increased intercapillary eosino philic material (ICE), ectatic capillaries, and thrombi. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal tubules or abnormal tubules was determined using a Chalkley point gri d. These quantal dose response data were analyzed using a logistic reg ression model. Results: Irradiation of the remaining kidney in UN monk eys resulted in a dose-dependent reduction in renal function and anemi a. Glomerular dysfunction preceded tubular dysfunction. Animals receiv ing 44 Gy all manifested progressive clinical renal failure. Conversel y, those receiving less than or equal to 39.6 Gy showed stable, albeit impaired, renal function for the duration of the observation period o f 107 weeks. Morphologically, the incidence of ICE, ectatic glomerular capillaries, thrombi, and periglomerular fibrosis was significantly d ose-related (p < 0.005). A significant (p < 0.001) dose-related increa se in the relative proportion of renal cortex occupied by abnormal tub ules was indicative of tubular injury. A highly significant (p < 0.001 ) dose-dependent increase in the proportion of abnormal to normal tubu les was also seen. Conclusion: The pathogenesis of radiation nephropat hy is difficult to fully understand because of the complex and dynamic interactions among all components of the nephron that make discrimina tion between primary radiation effects and secondary pathophysiologica l consequences very difficult. Notwithstanding, the current experiment shows that the functional and morphological expressions of radiation injury in the kidney are dose dependent. Renal failure occurs when bot h the glomeruli and tubules are dysfunctional. In monkeys following UN , a total dose of 44 Gy to the remaining kidney damages all components of the nephron and causes renal failure in less than 45 weeks. With l ower doses, changes to the glomeruli predominate and the animals survi ve. Kidney doses of up to 39.6 Gy/ 18 fractions of 2.2 Gy are compatib le with survival for at least 2 years in primates.