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 f unction and death with renal insufficiency as well as histopathologica l changes in the kidney was assessed. Single doses totaling 8-18 Gy we re given bilaterally to unanesthetized female and male C3Hf/Kam mice. Renal function damage was assayed by blood urea nitrogen (BUN) and hem atocrit (Hct). Histological damage was quantified by two parameters: k idney area and number of surviving tubule cells along the renal capsul e. The number of glomeruli was scored as an indication of the number o f nephrons. Changes in the two functional parameters did not appear so oner after irradiation in the nephrectomized mice than in the non-neph rectomized mice. Rather, less impairment of function was measured by b oth parameters in the nephrectomized mice but only after radiation dos es greater than 12 Gy. The LD(50) at 424 days after irradiation was al so higher in the nephrectomized mice than that in the mice receiving o nly irradiation, 13.98 Gy (95% confidence limits = 12.03, 15.93) and 1 1.71 Gy (95% confidence limits = 10.4, 13.1), respectively, in agreeme nt with the data on function. Unilateral nephrectomy alone induced a 1 0% increase in size of the contralateral kidney. The dose-response cur ve for the kidney area from nephrectomized mice was parallel to and di splaced above that for non-nephrectomized mice, indicating that the in crease in renal mass occurred independent of and was not compromised b y radiation. Unilateral nephrectomy alone induced no increase in the n umber of proximal tubules in the contralateral kidney. However, tubule survival was higher in nephrectomized mice given doses greater than 1 2 Gy compared with mice receiving only radiation. Fitting the tubule s urvival 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. Th ese data suggest that the improvement in renal function in mice nephre ctomized 24 h after irradiation of both kidneys compared to those rece iving only irradiation was due to tubule hyperplasia and not renal hyp ertrophy. Comparison of renal tubule counts and BUN in the same mouse at sacrifice showed a good correlation between cell depletion and chan ges in this functional parameter but only until tubule numbers reached values of 100 to 200, after which increases in BUN were not accompani ed by further decreases in the number of tubules. In conclusion, nephr ectomy 24 h after irradiation of both kidneys in mice did not precipit ate 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.