390 HERMAN O. MOSENTHAL 



not urea but ammonium carbamate derived from the urea. This has al- 

 ready been taken up in the previous section. The most recent investiga- 

 tions in regard to the effect of urea are those of Hewlett, Gilbert and 

 Wickett, who found that the ingestion of large amounts of urea (raising 

 the blood urea nitrogen as high as 111.4 mg. of urea nitrogen per 100 c.c.) 

 produces a certain train of symptoms comparable to those encountered 

 with marked renal insufficiency (asthenic type of uremia) : headache, diz- 

 ziness, apathy, drowsiness, bodily weakness, and fatigue. Such symptoms 

 appeared when the blood urea nitrogen rose above 68.2 per 100 c.c., and 

 disappeared when it fell below this level. These observations would indi- 

 cate that certain toxic phenomena could be ascribed to an accumulation 

 of urea in the blood. On the other hand, it is a common experience to 

 find blood urea values as given above, and even higher, while the patient 

 complains of no symptoms whatsoever. The writer has followed one such 

 case for almost two years and there are many other similar ones on record. 

 It is probable that the sudden flooding of the body with a substance, such 

 as urea, for the time being disturbs the existing osmotic relations, but if 

 the material accumulates more slowly, compensatory adjustments are made 

 that forestall the appearance of symptoms. That urea in itself, except 

 in huge amounts, should be responsible for the manifestations of renal 

 insufficiency, is therefore improbable. 



Creatinin has been considered as a possible causative agent of the 

 uremia brought on by renal insufficiency. What has been stated regard- 

 ing this substance under the heading of creatinin in nephritis may be re- 

 peated here. It is probable that creatinin in itself has little or no toxic 

 effect. This is demonstrated by the absence of untoward symptoms in 

 the numerous experiments on man and animals in which creatinin has 

 been injected or ingested. Myers and Killian(fr) believe that it may be 

 the cause of uremia. This, however, is based only upon theoretical grounds 

 and is contradicted by the evidence cited in the same paper that some cases, 

 with a high blood creatinin, survive a considerable length of 'time. A 

 rise in the blood creatinin certainly must be looked upon as a grave sign 

 of renal insufficiency. The kidney eliminates creatinin with great ease, 

 and this substance is therefore among the last of the end products of pro- 

 tein metabolism to be increased in the blood (see section on relation of uric 

 acid, urea and creatinin in the blood in nephritis). An augmentation of 

 creatinin in the blood is, however, only a signal of marked renal insuffi- 

 ciency ; in itself it has no further significance. The actual cause of uremia, 

 brought on by retention of waste products, can not be attributed to crea- 

 tinin but is to be sought in other substances which are simultaneously held 

 back by the damaged kidney. 



Creatin has been suggested at various times as a cause of uremia. As 

 stated under the heading of Creatin in Nephritis, it is probable that crea- 

 tin in increased amounts in the blood and to a lesser extent in the tissues, 



