Impaired function of neutrophils in uraemic patients

Immunodeficiency explains the very high frequency of bacterial infections in patients with chronic renal failure (CRF), which leads to high mortality and morbidity, despite improved therapeutic interventions. Among several factors, the decreased functional capacity of phagocytic leucocytes appears to be responsible for the defective host defence mechanisms against infection in CRF. We evaluated both oxygen-dependent and oxygen-independent microbicidal activity of neutrophils isolated from uraemic patients.

Forty patients with CRF (20 with mild-to-moderate CRF and 20 with advanced CRF) along with 20 age- and sex-matched healthy controls were studied. The assessment of phagocytic capability, ability to produce superoxide (O2.-) anion and H2O2, myeloperoxidase and granule-specific hydrolytic enzymes such as acid phosphatase, cathepsin D and lysozyme activity of the patient's neutrophils were performed to study their bactericidal activity.

The phagocytic index (PI) in the control group was found to be 50.38 (4.58). It was significantly reduced in both mild-to-moderate CRF and advanced CRF, as compared to controls. In mild-to-moderate and advanced CRF patients, O2.- production by resting polymorphonuclear neutrophils (PMN) was low. Also, on stimulation with PMA the O2.- production showed a relative reduction as compared to controls. H2O2 production by resting PMN from CRF patients was unaltered but on stimulation with PMA, the quantum of increase was significantly lower. A marked reduction in the level of intracellular myeloperoxidase activity in PMN was noted in CRF patients. Of the three intracellular lysosomal enzymes assayed, cathepsin D level was increased in the PMN of mild-to-moderate CRF patients; acid phosphatase level was elevated significantly in the PMN of both mild-to-moderate and advanced CRF patients. However, no change in lysozyme levels was observed.

With increasing severity of uraemia, neutrophils from uraemic patients showed progressive impairment of phagocytic ability. Impairment of oxygen-dependent microbicidal mechanisms was indicated by a decrease in O2.- and H2O2 production. Increased activity of lysosomal enzymes such as cathepsin D and acid phosphatase suggest a state of neutrophil activation in uraemia. It is likely that the immunodeficiency state in uraemics is partly due to reduced bactericidal activity of the neutrophil cell population.