Instability of immunoglobulins and complement (C3) as predictor of renal allograft rejection.

Ten renal allograft recipients were studied for a period of three months with weekly measurements of serum complement C3 including a baseline value before transplantation. Immunoglobulins (IgG, IgM, IgA) were studied in nine of these patients. Fifteen rejection episodes occurred, three patients losing their graft because of irreversible rejections. The patients were followed for 2.5 years. The degree of of change in serial C3 and immunoglobulin levels from baseline was determined by variability index s. Fourteen out of 15 rejections were preceded by si (C3) greater than .1, one to several weeks in advance. The si (Ig) was useful in week 1 and predicted the rejection missed by si (C3). We conclude that instability of immunoglobulins and complement as measured by s is not only associated with rejections but appears to be a precursor to rejection events. We suggest the following prognostic two-step procedure: (1) Week 1: If either si (C3) or si (Ig) greater than .1, predict rejection. (2) Cases that pass step 1 are monitored by C3 at weekly intervals. As soon as si (C3) greater than .1, predict rejection.

Identification of spermine as an inhibitor of erythropoiesis in patients with chronic renal failure.

Fetal mouse liver and normal human bone marrow cell cultures were used for studies on the inhibition of erythroid colony formation (CFU-E) by sera from anemic patients with end-stage renal failure and the polyamine spermine. Sera from each of eight predialysis uremic anemic patients with end-stage renal failure produced a significant (P < 0.001) inhibition of erythroid colony formation in the fetal mouse liver cell cultures when compared to sera from normal human volunteers. In vivo or in vitro dialysis of the uremic sera with a 3,500-dalton exclusion limit membrane removed the inhibitor from uremic sera. The uremic serum dialysate provided by the membrane fractionation was significantly inhibitory in the erythroid cell cultures. When this dialysate was applied to gel filtration chromatography (Bio-Gel P-2) the inhibitor was found to be in the same molecular weight range as [(14)C]spermine. The polyamine spermine produced a dose-related inhibition of erythroid colony formation (CFU-E) in fetal mouse liver and normal human bone marrow cultures. Thus, the following evidence is provided that the in vitro inhibitor of erythropoiesis found in chronic renal failure patients' sera is identical with the polyamine spermine: (a) the inhibitor and radiolabeled spermine appeared in identical Bio-Gel P-2 effluent fractions; (b) when spermine was added to normal human sera at concentrations reported in sera of uremic patients, and studied in both the fetal mouse liver cell culture and normal human bone marrow cultures, a dose-related inhibition of erythroid colony (CFU-E) formation was noted; and (c) the inhibitory effects of crude uremic serum, uremic serum dialysate, and fractions of uremic serum dialysate from a Bio-Gel column, on erythroid colony formation were completely abolished by the addition of a specific rabbit antiserum to spermine.