The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing.
BACKGROUND
Neutrophil functions in haemodialysis (HD) patients are altered by uraemia and by HD procedure. We investigated details of the neutrophil dysfunction as its nature and origin is not well understood. This is reflected by conflicting results about neutrophil phagocytosis activity and by scarce data on the neutrophil killing capability in HD patients.


METHODS
Using a flow-cytometric test system we have measured simultaneously phagocytosis and the production of reactive oxygen species (ROS) of neutrophils and in parallel antimicrobial killing of yeast by neutrophils. 117 whole-blood samples of healthy controls and 50 pre- and 50 post-dialysis samples of HD patients, half of them with diabetes mellitus (DM), have been evaluated. We have constructed a model to account for the dependence on the stimulus-to-cell ratio and obtain means for phagocytosis and killing at different incubation times.


RESULTS
(i) HD patients have significantly lower neutrophil killing (20%) than healthy controls. (ii) Dialysis improves the killing capability by 10-15%, after dialysis the killing activity remains significantly (10%) below that of the controls. (iii) The percentage of neutrophils, which exhibit phagocytosis and produce ROS, does not differ significantly between HD patients and healthy controls. (iv) Age has no significant influence on phagocytosis and killing.


CONCLUSIONS
The neutrophil killing capability is reduced in HD patients while the amount of neutrophils that phagocyte and produce ROS remains unchanged. Functional impairment of uraemic neutrophils is therefore mainly a result of their reduced capability to kill microorganisms intracellularly.
D000328:Adult; D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000032:analysis*; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods; D012307:Risk Factors; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D014511:Uremia / Q000150:complications*
D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species