[Investigations for pathogenesis of depression of lymphocyte transformation in chronic uremia (author's transl)]

In order to investigate the depressive effect of the hypothetical low molecular weight "uremic toxins" methylguanidine and phenol on lymphocyte transformation these substances were added to lymphocyte cultures with increasing concentrations. 3H-thymidine uptake and LDH-activity in the supernatant culture medium as a parameter of continuous cell destruction were analyzed after incubation for 5 days. Both substances induced in spontaneous as well as in PHA-stimulated cultures dose-dependent depression of 3H-thymidine uptake and simultaneous increase in LDH-activity. Thus the effect of both toxins may be cytotoxic depression of lymphocyte viability. Furthermore in the same arrangement-way higher molecular weight metabolites from urine of healthy and chronic uremic persons were added in increasing concentrations to lymphocyte cultures. The same result: dose-dependent depression of transformation and increase of LDH-activity was slightly diminished by urine metabolites from uremic patients as compared to healthy persons. This may be due to a shift toward non-toxic compounds. But as these metabolites are excreted in 20-30 fold larger quantities in chronic renal insufficiency, an accumulation in the serum and classification as "uremic toxins" can be excluded.