Factor D, an essential
enzyme of the alternative pathway (AP) of
complement, is eliminated by the kidney, and its plasma concentration increases 10-fold in
end-stage renal disease (
ESRD). The purpose of this study was to analyze the consequences of
factor D accumulation. A number of in vitro assays were used to analyze AP activation in normal human serum (NHS), in normal serum supplemented with purified
factor D to 10-fold its normal concentration (10 x D), and in sera of patients with
ESRD. When compared with NHS, in 10 x D: 1) Spontaneous fluid-phase activation of
complement at 37 degrees C was greatly increased as measured by C3 cleavage, 2) The lysis of rabbit erythrocytes, a function of the AP, was accelerated, 3) More C3 fragments bound to
cuprophane membranes and to
immune precipitates; both reactions were accompanied by the formation of more C5a, 4)
Complement mediated solubilization of
antigen-antibody precipitates was enhanced. Sera of patients with
ESRD behaved similarly to 10 x D in all assays used, i.e., enhanced AP function, although complement activation measured in these assays varied widely from one individual to another. Thus, the elevated
factor D concentration observed in
renal failure might have important pathophysiological consequences, some of which could be detrimental (e.g., C5a produced during
hemodialysis), while others might be beneficial, e.g., solubilization of
immune precipitates.