Renal Function in Man 23 



ciples of renal function, but it focusses attention again on 

 the importance of accurately measuring the rate of glomer- 

 ular filtration, for all subordinate calculations of what is 

 going on in the tubules in health or disease depend upon the 

 accuracy of this measurement. For this reason I would like 

 to return for a moment to the discussion of the inulin clear- 

 ance. I have spoken of our continued efforts to obtain fur- 

 ther evidence on the mechanism of the excretion of inulin. 

 The difficulties in this problem lie in obtaining substances for 

 which accurate methods of analysis in blood and urine are 

 available, and in the selection of substances which have suit- 

 able physiological properties. The field is narrowed by the 

 fact that the renal tubules are known to reabsorb or excrete 

 so many different types of compounds. Strong electrolytes 

 are handled by the tubules in a complex manner, and many 

 weak electrolytes (uric acid, creatinine, amino acids, etc.) 

 presumably become entangled in these tubular processes or 

 are themselves handled by specific reactions. Even though a 

 weak electrolyte might escape tubular reabsorption or excre- 

 tion in the normal kidney, or under special circumstances, 

 there is no assurance that it would remain inviolable under 

 all circumstances, or in the nephron with perturbed func- 

 tion. In our further search, therefore, we have concentrated 

 upon substances which have as little chemical reactivity as 

 possible, for in theory we would like a molecule that was ab- 

 solutely chemically inert, and one endowed with such physi- 

 cal properties that it would not diffuse through a normal or 

 even a moderately injured cell. We have recently had under 

 examination the polyhydric alcohols, sorbitol and mannitol, 

 in the belief that these represent a step in the right direction. 

 Dr. W. W. Smith has recently devised methods for the analy- 

 sis of such compounds in blood and urine, and in a limited 



