A. Dhondt

Depressed Phagocytosis in Hemodialyzed Patients: In vivo and in vitro Mechanisms

Infection is a frequent complication and the major cause of death among end-stage renal patients. Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis. In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients. Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Staphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples. These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C. This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA. PMNL response remains intact during dialysis with non-complement-activating dialyzers. In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood. We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure. The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions. These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients.

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry

UNLABELLEDnThrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients.nnnMATERIALS AND METHODSnData were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry.nnnRESULTSnThe mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034).nnnCONCLUSIONSnPatients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels.

Association of advanced age with concentrations of uraemic toxins in CKD

To our knowledge, there are no studies on advanced chronic kidney disease (CKD) analysing the impact of ageing on serum concentrations of uraemic toxins while adjusting for renal function. Knowledge of this feature, however, could influence prognostic assessment and therapeutic decision-making, e.g. about when to start dialysis or how intensive it should be. Indeed, the slowing down of metabolism with age may result in lower uraemic toxin concentrations, hence reducing their toxic effects. In this case, a later start of dialysis or less intensive dialysis may become justified in an already fragile population that might enjoy a better quality of life without a survival disadvantage with conservative treatment. We assessed the impact of advancing age on uraemic solute concentrations [blood, urea, nitrogen (BUN), uric acid, creatinine, asymmetric and symmetric dimethylarginine (ADMA and SDMA), β2-microglobulin and a large array of protein-bound solutes] by matching 126 maintenance haemodialysis patients subdivided into two age-groups, younger vs. older (using the median as cut-off: 72xa0years). Concentrations were compared after age stratification and were matched with patient and dialysis characteristics. In addition, 93 non-dialysed CKD patients (median as cut-off: 70xa0years), with a comparable average estimated glomerular filtration rate (eGFR) between younger and older age-groups, were analysed. In haemodialysis patients, carboxy-methyl-furanpropionic acid (CMPF) levels were markedly higher and BUN and uric acid borderline lower in the older age-group. All other solutes showed no difference. At multifactor analysis, the concentration of several uraemic toxins was associated with residual renal function and protein intake in the overall haemodialysis group and the younger group, but the association with most solutes, especially those protein-bound, was lost in the older age-group. No differences were found in non-dialysed CKD patients. It was concluded that in this CKD population concentrations of uraemic toxins did not change substantially with calendar age.