Renotrophic factors in urine

Harris, Robert H.; Hise, Michael K.; Best, Christopher F.
April 1983
Kidney International;Apr1983, Vol. 23 Issue 4, p616
Academic Journal
Our previous observations of increased renal protein synthesis in rats subjected to the constant intravenous reinfusion of half their urine output has suggested that the circulatory retention of renotrophic factors in urine is capable of stimulating renal growth. In the present studies, using this same model of ‘half-urine-reinfusion,’ which is designed to produce a selective halving of renal excretory function, we have demonstrated significant increases in total DNA content and the incorporation of tritiated thymidine in renal DNA. In addition, a bioassay method was developed in which an assay rat, given an intravenous infusion of urine from another rat, exhibited increases in the incorporation of thymidine into renal DNA and the incorporation of radiolabelled choline into renal phospholipid. This renotrophic activity in the urine was only minimally decreased by heating to 100°C for 30 min and was confined to ultrafiltration fractions retained on a membrane with a nominal 10,000-dalton solute rejection. Removal of one kidney from the rats from which the urine was obtained led to only a modest and transient reduction in the excretion of renotrophic activity, suggesting that the urinary renotrophic factors are of circulatory, not renal, origin. Isolated renal cortical fragments incubated with an ultrafiltration retentate of urine displayed a dose-dependent increase in choline incorporation into phospholipid, suggesting a direct action of the tractors on kidney tissue. Finally, no evidence of stimulation of either DNA or phospholipid synthesis could be seen in hepatic tissue. In conclusion, our data support the concept that there are renotrophic factors normally excreted in urine; that these factors are capable of stimulating renal synthesis of protein, DNA, and phospholipid: that the factors are of medium to large molecular size and are largely heat-stable; that they appear to have extra-renal origin(s); and that they are specific for the kidney to the extent that they do not stimulate hepatic growth. Retention of these factors may provide an important stimulus to renal growth following ablation of renal mass.


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