Impaired function of macrophage Fc gamma receptors in end-stage renal disease

Abstract

Infection is a frequent complication in patients undergoing hemodialysis for end-stage renal disease and is the primary cause of mortality among such patients. Macrophages are important in host defense against infection largely because their Fc gamma receptors recognize antibody-coated bacteria. We therefore studied macrophage Fc gamma-receptor function in vivo and in vitro in 56 patients with end-stage renal disease who were on hemodialysis and in 20 healthy volunteers. The clearance of IgG-coated (sensitized) autologous red cells was decreased in 53 patients. The inhibition of clearance in the 56 patients was 52 +/- 3 percent at 1 hour, 41 +/- 5 percent at 1 1/2 hours, and 29 +/- 5 percent at 2 hours (P less than 0.001). The clearance of unsensitized erythrocytes and heat-altered autologous erythrocytes was normal. The impairment of clearance was not correlated with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis. Nine patients had severe infections during a two-year follow-up period. The clearance of IgG-coated cells in these patients (half-time, 12.9 +/- 1.7 hours) was significantly impaired, as compared with that in the 47 patients without severe infections (half-time, 4.4 +/- 1.8 hours; P less than 0.001). We conclude that macrophage Fc gamma-receptor function is impaired in patients with end-stage renal disease who are undergoing hemodialysis, and that this impairment probably contributes to the observed immunodepression and high prevalence of infection among such patients.