Factors in the dialysis regimen which contribute to alterations in the abnormalities of uremia.

While hemodialysis therapy in its present form is capable of sustaining life, dialysis patients are not metabolically normal and we are unable to say what technical factors contribute adequate therapy. Recent efforts to resolve these problems have led to the assumption that substances in the molecular weight range of 800 to 3000 daltons may be pathogenic in uremia and these may not be effectively removed by dialysis. Accordingly, four groups of patients (ten each) underwent changes in their routine which were theoretically designed to alter independently the concentration of small (urea) and "middle" molecules in the blood. In two groups, the concentration of urea was theoretically increased or decreased while the concentration of so-called middle molecules was maintained unchanged. In the remaining two groups, middle molecule concentration was theoretically increased or decreased while small molecule concentration was unchanged. Patients were evaluated prior to and after completing altered dialysis therapy. The results suggest three related conclusions. First, the uremic syndrome may be viewed as a constellation of abnormalities which can be subgrouped by association so that azotemia may be correlated with neuropathic disease and hypertension with weight gain or body size, for example. Second, those physiologic variables which changed after altered dialysis tended to deteriorate with increasing concentration of small molecules in the blood and remained independent of theoretical changes in middle molecules. Finally, when patients are relatively under-dialyzed, they may spontaneously modulate the reduced removal of metabolites such as urea by decreasing the dietary intake of nutrients.