Radiation response of the monkey kidney following contralateral nephrectomy.
OBJECTIVE
The long-term functional and morphologic responses of the hypertrophied monkey kidney after unilateral nephrectomy to fractionated irradiation were assessed.


METHODS
The right kidney of 13 adult female rhesus monkeys was removed. Twelve weeks after unilateral 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 nitrogen, serum creatinine, and hematocrit values were measured up to 107 weeks postirradiation (PI). The monkeys were killed and the remaining kidneys were removed 107 weeks PI or earlier when end-stage renal failure was exhibited. Glomeruli were scored for the presence/absence of several pathologic features including increased intercapillary eosinophilic 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 grid. These quantal dose response data were analyzed using a logistic regression model.


RESULTS
Irradiation of the remaining kidney in UN monkeys resulted in a dose-dependent reduction in renal function and anemia. Glomerular dysfunction preceded tubular dysfunction. Animals receiving 44 Gy all manifested progressive clinical renal failure. Conversely, those receiving < or = 39.6 Gy showed stable, albeit impaired, renal function for the duration of the observation period of 107 weeks. Morphologically, the incidence of ICE, ectatic glomerular capillaries, thrombi, and periglomerular fibrosis was significantly dose-related (p < 0.005). A significant (p < 0.001) dose-related increase in the relative proportion of renal cortex occupied by abnormal tubules was indicative of tubular injury. A highly significant (p < 0.001) dose-dependent increase in the proportion of abnormal to normal tubules was also seen.


CONCLUSIONS
The pathogenesis of radiation nephropathy is difficult to fully understand because of the complex and dynamic interactions among all components of the nephron that make discrimination between primary radiation effects and secondary pathophysiological 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 both 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 lower doses, changes to the glomeruli predominate and the animals survive. Kidney doses of up to 39.6 Gy/18 fractions of 2.2 Gy are compatible with survival for at least 2 years in primates.
Robbins
M E
ME
CRC Normal Tissue Radiobiology Research Group, Research Institute (University of Oxford), Churchill Hospital, UK.
Stephens
L C
LC
Thames
H D
HD
Gray
K N
KN
Peters
L J
LJ
Ang
K K
KK
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005919:Glomerular Filtration Rate / Q000528:radiation effects; D007668:Kidney / Q000473:pathology / Q000528:radiation effects*; D008253:Macaca mulatta; D009392:Nephrectomy; D012079:Renal Circulation / Q000528:radiation effects