July 27, 1945

Dr. T. Addis

Stanford University

School of Medicine

2398 Sacramento Street

San Francisco, California

Dear Dr. Addis:

I am pleased to see the results that you got from your dialysis experiment. It is clear that there is equilibrium between salt in the urine and in the plasma when the concentrations are within about 10 per cent of one another. I don't know whether or not the 10 per cent excess indicated for the urine by your experimental results is significant, but I don't think that it matters. I know that George Scatchard at MIT has carried out some similar experiments with serum albumin—since getting home, I have found reference to this work in the book on proteins by Cohn and Edsall. Since I can't find the data anywhere, I have written to Scatchard, asking him what salt concentration would be in membrane equilibrium with normal plasma. We should have a reply in a few days.

The only thing that I don't understand about your experiment is the statement on the graph that the cellophane bags of serum all floated in the middle of the salt solution. If the salt solution had been well mixed, a serum bag should either drop clear to the bottom or float on the top; the only way that a bag would be suspended half way down is by having the salt solution not well mixed, so that at the bottom the salt concentration and hence the density were greater than at the top.

I enclose another page of calculations on the work of the kidney. These are in two parts, first, the work due to urea, and second, that due to sodium chloride. You will see that, as before, we find that, for grams of protein ingested, there is a saving of l64 calories for 36 per cent of the work due to urea concentration on increasing the urine volume from one liter to 3 liters. This is equivalent to the saving on decreasing protein intake from 44 grams to 23 grams. A further saving of 39 calories, equivalent to a decrease in protein intake of 4 grams., would be made in the urea work by going from 3 liters to 4 liters in urine volume.

With respect to sodium chloride, the work due to sodium ions and chloride ions is small so long as the salt concentration in the urine is approximately equal to that of the plasma. Everything is fine so long as the salt concentration in the urine does not deviate by more than about 25 per cent from that in the plasma. If it drops to only one half that in the plasma, the increased work due to salt counterbalances the saving due to urea at about 3 liters urine volume.

These calculations, then, indicate strongly that the urine volume should be kept up to 3 liters, and the salt intake should be increased in such a way that the salt concentration in the urine is 5 grams per liter or more. Only if there were some evidence that increased salt is harmful would this recommendation be unwise, and I don't know of any such evidence. The equation indicates that there would be further saving in work by going to a urine volume of 4 liters, provided that the salt concentration is kept up to 5 grams per liter. If it drops to 3 grams per liter, however, there would be no such saving in work on going from 3 to 4 liters.

I propose that, if you think it not unwise, I myself increase the amount of salt ingested to about the optimum salt concentration in the urine, which minimizes the osmotic work of the kidney, might be obtained from patients with Addison's disease. Do you know whether or not these patients show a constant ratio of salt concentration in urine and plasma?

I enjoyed my visit with you immensely.

Sincerely yours,

Linus Pauling

LP:jr

Enclosure