Polymorphonuclear cell function and infection in dialysis.
End-stage renal disease is characterized by enhanced susceptibility for infectious diseases, carrying an important risk of morbidity and mortality. In the host's defense against bacterial infection, a central role is played by phagocytic ingestion of bacteria, followed by their destruction after metabolic production of oxygen free radical species. Our studies have concentrated on the energy delivery by the hexose monophosphate shunt (HMS) to NAD(P)H-oxidase, the enzyme responsible for free radical production. This evaluation was realized by measuring, in whole blood, the CO2 produced from standard quantities of radiolabeled glucose, with data normalized for the number of polymorphs in each sample. Our studies indicate that: (1) glycolysis is disturbed in uremic outpatients from a SCrea of 6 mg/dl and a CCr of 15 ml/min; (2) similar functional disturbances are found in pre-dialysis blood samples of hemodialyzed patients; (3) this functional disturbance is further intensified during dialysis with cuprophan, which is not the case for non-complement activating dialyzers; (4) the response is especially suppressed towards Staphylococcus Aureus, the bacterial species responsible for the majority of infections in uremia; (5) that functional disturbances are mainly related to uremic toxicity, dialyzer membrane bio(in)compatibility, and uremic anemia. Biochemical disturbances in PMNL, induced by a multifactorial patho-physiologic process, may therefore be related to the enhanced incidence of infection in uremic patients.
Vanholder
R
R
Nephrology Department, University Hospital, Ghent, Belgium.
Ringoir
S
S
D006019:Glycolysis; D006648:Histocompatibility; D006801:Humans; D007239:Infections / Q000209:etiology*; D007501:Iron / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000378:metabolism
D007501:Iron