UNILATERAL NEPHRECTOMY 24 HOURS AFTER BILATERAL KIDNEY IRRADIATION REDUCES DAMAGE TO THE FUNCTION AND STRUCTURE OF THE REMAINING KIDNEY

The effect of unilateral nephrectomy 24 h after irradiation on renal function and death with renal insufficiency as well as histopathological changes in the kidney was assessed. Single doses totaling 8-18 Gy were given bilaterally to unanesthetized female and male C3Hf/Kam mice. Renal function damage was assayed by blood urea nitrogen (BUN) and hematocrit (Hct). Histological damage was quantified by two parameters: kidney area and number of surviving tubule cells along the renal capsule. The number of glomeruli was scored as an indication of the number of nephrons. Changes in the two functional parameters did not appear sooner after irradiation in the nephrectomized mice than in the non-nephrectomized mice. Rather, less impairment of function was measured by both parameters in the nephrectomized mice but only after radiation doses greater than 12 Gy. The LD(50) at 424 days after irradiation was also higher in the nephrectomized mice than that in the mice receiving only irradiation, 13.98 Gy (95% confidence limits = 12.03, 15.93) and 11.71 Gy (95% confidence limits = 10.4, 13.1), respectively, in agreement with the data on function. Unilateral nephrectomy alone induced a 10% increase in size of the contralateral kidney. The dose-response curve for the kidney area from nephrectomized mice was parallel to and displaced above that for non-nephrectomized mice, indicating that the increase in renal mass occurred independent of and was not compromised by radiation. Unilateral nephrectomy alone induced no increase in the number of proximal tubules in the contralateral kidney. However, tubule survival was higher in nephrectomized mice given doses greater than 12 Gy compared with mice receiving only radiation. Fitting the tubule survival data by maximum likelihood analysis gave D-0's of 6.7 Gy (95% confidence limits = 6.3, 7.1 Gy) and 3.7 Gy (95% confidence limits = 3.5, 3.8 Gy) for the irradiated nephrectomized mice and irradiated mice, respectively. However, the number of glomeruli was the same for both groups, suggesting that the number of the nephrons did not change. These data suggest that the improvement in renal function in mice nephrectomized 24 h after irradiation of both kidneys compared to those receiving only irradiation was due to tubule hyperplasia and not renal hypertrophy. Comparison of renal tubule counts and BUN in the same mouse at sacrifice showed a good correlation between cell depletion and changes in this functional parameter but only until tubule numbers reached values of 100 to 200, after which increases in BUN were not accompanied by further decreases in the number of tubules. In conclusion, nephrectomy 24 h after irradiation of both kidneys in mice did not precipitate either impaired function or histological damage. Rather, impaired function was less in the nephrectomized irradiated mice compared with those only irradiated, which was due at least in part to the increased tubule survival in the nephrectomized mice.