Quality of life as indicator of poor outcome in hemodialysis: relation with mortality in different age groups.

BACKGROUND: Physical, cognitive and psychosocial functioning are frequently impaired in dialysis patients and impairment in these domains relates to poor outcome. The aim of this analysis was to compare the prevalence of impairment as measured by the Kidney Disease Quality of Life- Short Form (KDQOL-SF) subscales between the different age categories and to assess whether the association of these subscales with mortality differs between younger and older dialysis patients. METHODS: This study included data from 714 prevalent hemodialysis patients, from 26 centres, who were enrolled in the CONvective TRAnsport STudy (CONTRAST NCT00205556, 09-12-2005). Baseline HRQOL domains were evaluated for patients <65 years, 65-74 years and over 75 years. Multivariable Cox proportional hazards analyses were performed to assess the relation between the separate domains and 2-year mortality. RESULTS: Emotional health was higher in patients over the age of 75 compared to younger patients (mean level 71, 73 and 77 for increasing age categories respectively, p = 0.02), whilst physical functioning was significantly lower in older patients (mean level 60, 48 and 40, p < 0.01). A low level of physical functioning (Hazard Ratio (HR) 1.72 [95%Confidence Interval (CI) 1.02-2.73]), emotional health (HR 1.85 [95% 1.30-2.63]), and social functioning (HR 1.59 [95% CI 1.12-2.26]), was individually associated with an increased 2-year mortality within the whole population. The absence of effect modification suggests no evidence for different relations within the older age groups. CONCLUSIONS: In dialysis patients, older age is associated with lower levels of physical functioning, whilst the level of emotional health is not associated with age. KDQOL-SF domains physical functioning, emotional health and social functioning are independently associated with mortality in prevalent younger and older hemodialysis patients.

Hepcidin in chronic kidney disease: not an anaemia management tool, but promising as a cardiovascular biomarker.

Hepcidin is a key regulator of iron homeostasis and plays a role in the pathogenesis of anaemia of chronic disease. Its levels are increased in patients with chronic kidney disease (CKD) due to diminished renal clearance and an inflammatory state. Increased hepcidin levels in CKD patients are supposed to be responsible for functional iron deficiency in these patients and contribute to renal anaemia and resistance to erythropoiesis-stimulating agents. Therefore, hepcidin was purported to be useful as a management tool guiding treatment of renal anaemia. Furthermore, since hepcidin is associated with iron accumulation in macrophages in the vessel wall inducing oxidative stress and atherosclerosis, it has been speculated that hepcidin might function as a biomarker of cardiovascular disease. In this descriptive review, the merits of hepcidin with respect to its role in the pathophysiology of renal anaemia in CKD patients, its presumptive role as a practical diagnostic tool guiding management of renal anaemia, and its possible usefulness as a prognostic biomarker will be discussed.

[New study evaluating online haemodiafiltration for the reduction of cardiovascular morbidity and mortality in patients undergoing chronic haemodialysis]. / Nieuw onderzoek naar online-hemodiafiltratie voor de vermindering van cardiovasculaire morbiditeit en mortaliteit bij patiënten die chronisch worden behandeld met hemodialyse.

Removal of uraemic toxins can be increased by online haemodiafiltration. At present, it is unclear whether online haemodia-filtration ultimately improves clinical outcomes in chronic haemodialysis patients. The Dutch 'Convective transport study' (CONTRAST) is an ongoing trial comparing standard haemodialysis with online haemodiafiltration. This randomised controlled trial will provide substantial clinical evidence on the effects of haemodiafiltration on fatal and non-fatal cardiovascular events and all-cause mortality, compared with standard haemodialysis.

Reverse epidemiology: paradoxical observations in haemodialysis patients.

Traditional risk factors, such as high blood pressure (BP), obesity and hypercholesterolaemia, play an important role in the development of cardiovascular disease (CVD), not only in the general population but also in patients with chronic renal disease. In recent years, it has become less clear whether these conventional risk factors are responsible for the extremely high risk of CVD in chronic haemodialysis (CHD) patients. Recent studies have shown that low BP, body mass index (BMI) and serum cholesterol are often correlated with an unfavourable clinical outcome. Thus, whereas traditional risk factors of CVD are correlated with an unfavourable outcome in the general population and patients with chronic renal failure not yet on dialysis, in CHD patients these factors appear to be protective and associated with an improved survival. Therefore, these phenomena have been referred to as 'paradoxical or reverse epidemiology'. The aetiology of this inverse relationship is not clear. Interestingly, in CHD patients, both C-reactive protein, a marker of inflammation, and (pre)albumin, a marker of nutrition, are important independent predictors of mortality. It has been speculated that what is known as the malnutritioninflammation-atherosclerosis complex underlies, at least partly, the phenomenon of reverse epidemiology, since malnutrition causes a low BMI and hypocholesterolaemia. Hence, besides care for adequate nutrition, attempts should be made to reduce inflammation. In this respect, various haemodialysis-related factors, such as the purity of the dialysate and several characteristics of the dialyser, deserve attention.

Relationships between undernutrition prevalence among children and adult women at national and subnational level.

OBJECTIVES: The objective of this study is to analyze the relationships between undernutrition prevalence rates among children and adults, both at the level of countries and at the level of smaller geographical subunits within countries (districts, provinces). Results are considered of relevance for evaluation and proper usage of anthropometric information in poverty and food security assessment. DESIGN: Anthropometric information on both children and adults, as reported in the Demographic and Health Surveys, has been the primary source of data. In addition, data published by WHO, FAO, and data from some country specific reports have been used. The final analysis is based on data from 289 subnational geographical units divided over 56 countries in Africa, Asia and Latin America. Ordinary least squares has been used for regression analysis and F-tests for testing differences of variances. RESULTS: At the level of countries, results reveal a strong positive relationship between undernutrition prevalence rates among children and adults. At the level of smaller geographical units, high levels of undernutrition in adult women are almost invariably associated with high levels of undernutrition in children. At the same time, however, low or intermediate levels of undernutrition among adult women are no guarantee that undernutrition levels among children are also low or moderate. CONCLUSION: At the level of countries, information on undernutrition prevalence in children can be considered a proximate of the overall nutritional and food security conditions in a country. At the level of smaller geographical units, relationships are less straightforward, and are hypothesized to depend, at least partially, on the relative importance of food and nonfood factors in the causation of undernutrition.

Deviations in coagulation activation due to treatment with different haemodialysis membranes.

Despite systemic heparinization, extracorporeal circulation will induce activation of blood coagulation. Thrombogenicity is associated with biocompatibility of dialysis membranes. Investigation of procoagulatory and fibrinolytic activity is performed prior to and during treatment with haemodialysis. In this study fluctuations of plasma coagulation factor XII, thrombin antithrombin complexes, prothrombin fragment 1 + 2 and thrombus precursor protein were monitored in 10 subjects during treatment with haemodialysis. Subjects were treated with both polysulphone high-flux dialyser membranes (F-60) and low-flux poly-methyl-methacrylate (PMMA) membranes. Immediately after start of treatment, blood in contact with artificial membrane surfaces resulted in a marked decrease in factor XII activity amounting to a mean reduction of 80% in the case of PMMA and a reduction of 40% in the case of F-60. In due course, a steady, on-going generation of thrombin antithrombin complexes was observed in several subjects, especially after treatment with F-60 membranes, amounting to increases exceeding 100% of initial values. Establishment of fibrinogen, prothrombin fragment 1 + 2 and thrombus precursor protein plasma concentrations yielded enhanced results for PMMA compared with the results for treatment with F-60 dialysis membranes. In order to prevent activation of clotting during several stages of haemodialysis, supplementation of anticoagulant can be established on the basis of analytical results of coagulation parameters.

Gender and adult undernutrition in developing countries.

BACKGROUND: Information on the prevalence of undernutrition in adults in developing countries is mainly restricted to data on women. Literature reporting on the occurrence of female deprivation in developing countries, in particular in South Asia, suggests that differences between undernutrition prevalence in adult men and adult women might occur, but systematic information on the subject is lacking. AIM: The study compares undernutrition prevalence rates, based on prevalence of low body mass index (BMI < 18.5), in adult men and adult women in developing countries. Regional comparison is made between the main developing regions: Sub-Saharan Africa, South/Southeast Asia and Latin America. SUBJECTS AND METHODS: The study uses data as reported in 75 samples from 31 countries(divided over the three developing regions), in which anthropometric information has been collected in adult men and women within one and the same community. RESULTS: Results indicate that, in general, prevalence rates of undernutrition are rather similar in adult men and women. However, there are regional differences. In communities in Sub-Saharan Africa, prevalence of low BMI is, on average, a few percent higher in men than in women; in South/Southeast Asia the reverse is the case. In some communities differences in undernutrition prevalence between men and women are exceptionally large. CONCLUSIONS: It can be concluded that, in general, information on undernutrition prevalence in women can be considered a proxy for undernutrition prevalence in all adults, men and women together. However, the finding that in South/Southeast Asia women's nutritional status relative to men's nutritional status compares unfavourably with results from other developing regions, in particular Sub-Saharan Africa, provides some support for the concept of female deprivation in South/Southeast Asia. Where large differences between prevalence of low BMI in men and women occur, gender-specific policies aimed at reducing under-nutrition should be considered.

Monocyte activation in peripheral blood and dialyser eluates: phenotypic profile and cytokine release.

BACKGROUND/AIMS: Monocyte activation and subsequent cytokine generation is presumed to be involved in haemodialysis (HD)-related morbidity. The present study was designed to investigate HD-induced changes in monocytes, with respect to their phenotypic profile and cytokine release, both in peripheral blood (PB) and dialyser eluates (DE). In addition, the effect of the type of dialyser on monocyte activation was assessed. METHODS: Dialyser elution was performed in 8 patients after 3 h of HD, using cuprammonium (CU) and polysulfon (PS) dialysers in a randomised cross-over design. PB samples and DE were analysed for both the expression of a variety of monocyte cell surface markers (CD62L, CD11b, CD25, HLA-DR, CD64 and CD14) by flow cytometry and IL-1beta levels. Monocytes were identified by dual labelling with antibodies against CD14. RESULTS: In PB, the expression of CD11b increased during HD with both devices, but was more pronounced with CU (CU versus PS: p < 0.05). CD62L decreased during HD, but only significantly for PS (p < 0.02). HLA-DR was downregulated during HD with CU (p = 0.056). The expression of CD64 was higher during HD with CU (p = 0.02). Finally, CD14 increased during HD with both dialysers (p < 0.03). DE yielded a mean cell count of 51 x 10(6) cells. The proportion of monocytes in DE was 3% for CU and 4% for PS. In eluted monocytes, a significant upregulation of CD11b, CD25, and HLA-DR was observed. CD62L was downregulated when compared to PB at t(180) (p < 0.001). In DE, no correlation was found between the type of dialyser and the phenotypic changes. In 10 of 16 DE supernatants, 6 CU and 4 PS, IL-1beta release could be demonstrated, CU yielding significantly more of this cytokine than PS (p = 0.03). CONCLUSIONS: According to both their phenotypic profile and cytokine release, monocytes sticking to the dialyser membrane after HD are considerably more activated than circulating monocytes. Activation of eluted monocytes appeared independent of the type of dialyser, suggesting an effect of mechanical stress rather than bioincompatibility. In contrast, phenotypic activation of peripheral blood monocytes and cytokine release in the DE supernatant were mainly dialyser-dependent.

Long-term reduction of plasma homocysteine levels by super-flux dialyzers in hemodialysis patients.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease in chronic hemodialysis (CHD) patients. Treatment with folic acid normalizes total homocysteine (tHcy) in only a minority of the patients. The present investigation has been conducted to study the influence of various dialyzers with different flux characteristics on the reduction of tHcy in the long term. METHODS: Total Hcy, folate, vitamin B6, vitamin B12, and albumin levels were assessed prospectively in 10 patients undergoing HD with high-flux polysulfon (PS; F 60) and 20 patients with super-flux dialyzers (N = 10 PS, F 500S; N = 10 CTA, Tricea 150G). Blood samples were collected before hemodialysis both at the beginning of the study and after 12 weeks. RESULTS: At baseline, all the groups showed similar tHcy levels. During high-flux dialysis, tHcy remained stable. In contrast, during dialysis with both super-flux modalities, tHcy decreased significantly (F 500S week 1, 29.6 +/- 9.9 micromol/L, and week 12, 21.5 +/- 8.5 micromol/L, P = 0.007; Tricea 150G week 1, 24.4 +/- 8.7 micromol/L, and week 12, 15.3 +/- 3.7 micromol/L, P = 0.008). The difference between high-flux and super-flux dialyzers was highly significant (mean: high-flux increase 15.6%, super-flux decrease 33. 3%, P = 0.001). Multivariate analysis showed a significant effect of super-flux dialysis on tHcy (P = 0.001), independently of the previously mentioned variables. CONCLUSIONS: Our findings clearly show that both types of super-flux dialyzers reduced tHcy significantly. As the molecular weight of free homocysteine is less than 268 D, the most likely explanation seems to be the removal of uremic toxins with inhibitory activities against enzymes involved in the extrarenal homocysteine metabolism.

Activation of coagulation during treatment with haemodialysis.

Generation of factor XII, thrombin antithrombin complexes, prothrombin fragment 1+2 and thrombus precursor protein has been monitored in 16 subjects during haemodialysis. Immediately after starting treatment, contact of blood with the negatively charged surfaces of the polyacrylnitril membrane AN-69 resulted in a 9-45% decrease in factor XII activity. Peak concentrations for thrombin antithrombin complexes (50 to 120 microg/L) were observed 30 min after the start of haemodialysis. Establishment of thrombus precursor protein concentrations yielded steadily increasing results without any tendency to decrease during treatment. Determination of thrombin antithrombin complexes is considered to establish the most sensitive short-term reacting parameter indicating activation of coagulation. A steady generation of fibrin and fibrinogen-fibrin complexes during treatment with haemodialysis is indicated by increasing results for thrombus precursor protein. In order to prevent clotting during haemodialysis, an additional supplementation of anticoagulant is needed.

Hemodialysis-induced degranulation of polymorphonuclear cells: no correlation between membrane markers and degranulation products.

BACKGROUND/AIMS: Degranulation of polymorphonuclear leukocytes (PMN) during hemodialysis (HD) is usually assessed by measuring degranulation products. However, this process might also be estimated by the assessment of cell surface markers. In this study, the relationship between the expression of PMN degranulation markers (CD63 and CD66b) and the release of degranulation products [myeloperoxidase (MPO) and lactoferrin (LF)] was investigated during clinical HD in order to evaluate cell surface markers as a useful index of PMN degranulation. METHODS: The expression of CD63 and CD66b on PMN and the release of MPO and LF were investigated in 10 chronic HD patients, during both heparin (HDhep) and trisodium citrate anticoagulation (HDcit), in a randomized order. Samples were drawn from both the efferent and afferent lines of the dialyzer at 0, 7.5, and 180 min. RESULTS: During HDhep at first passage, a major increase in MPO (from 158 +/- 32 to 448 +/- 177 microg/l, p = 0.001) and LF (from 134 +/- 52 to 260 +/- 120 microg/l, p = 0.01) was found across the dialyzer, whereas marked changes were not observed during HDcit. The expression of CD63 and CD66b increased across the dialyzer during both anticoagulation modalities, but was only significant in the case of HDhep (CD63: mean fluorescence intensity from 247 +/- 61 to 331 +/- 118, p < 0.01; CD66b: mean fluorescence intensity from 340 +/- 76 to 434 +/- 103, p = 0.01). During HDhep a correlation was noted between the degranulation products and markers of both azurophilic and specific granules (MPO and CD63: r = 0.35; p < 0.01; LF and CD66b: r = 0.39, p < 0.01). Significant differences in the expression of CD63 and CD66b between HDhep and HDcit were not observed. When analyzing the combined data for both HDhep and HDcit, no correlation was observed between degranulation products and markers. CONCLUSION: Our data suggest that the measurements of cell surface markers may not be a reliable indicator of the degree of HD-induced PMN degranulation.

Effects of dialyser and dialysate on the acute phase reaction in clinical bicarbonate dialysis.

BACKGROUND: In chronic haemodialysis (HD), morbidity may result from repetitive induction of the acute phase response, caused by a bioincompatible dialysis membrane and/or contaminated dialysate. In the present study, cytokine release (interleukin-6, IL-6) and subsequent production of acute phase proteins (C-reactive protein, CRP and secretory phospholipase A(2), sPLA(2)) were assessed to investigate whether the HD-induced acute phase reaction depends mainly on the type of membrane or on the sterility of the dialysate. METHODS: In 11 patients, IL-6, CRP and sPLA(2) levels were assessed in blood samples drawn before (t(0)), at the end (t(180)) and 24 h after the start of HD (t(1440)). All patients were dialysed on Cuprammonium (CU) and Polysulphon (PS) dialysers and seven patients underwent an additional HD session on CU plus a dialysate filter (CUf). RESULTS: IL-6 levels were increased significantly at t(180) compared with t(0) (P<0.02) with both CU and CUf. At t(1440), IL-6 levels had returned to baseline. In contrast, marked fluctuations did not occur during HD with PS. At t(180), IL-6 was significantly greater with CU and CUf devices, than with PS (P<0.02). Following HD with CU and CUf, a significant increase in CRP was observed at t(1440), compared with postdialysis values (P

[Proatherogenic changes induced by hemodialysis; probably a result of bio-incompatibility]. / Proatherogene veranderingen door hemodialyse; mogelijk een gevolg van bio-incompatibiliteit.

Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular disease, which can only in part be explained by known risk factors such as dyslipidaemia, hypertension, hyperhomocysteinemia, diabetes mellitus and chronic volume expansion. A possible cause is that the haemodialysis treatment itself contributes to the accelerated atherosclerosis, observed in these patients. Nowadays, atherosclerosis is considered an inflammatory process, mediated by a dysfunction of the vascular endothelium. As a result, blood cells adhere to the vascular surface and release a variety of vasoactive mediators, cytokines, growth factors and free radicals. Due to the contact between blood and dialyzer, humoral systems and cellular elements are stimulated, and this may be viewed as an inflammatory reaction. As a consequence of this, the vascular surface of haemodialysis patients is repeatedly exposed to the influences of cytokines, coagulation products, vasoactive mediators, stimulated leukocytes and thrombocytes, and oxidative stress. It is therefore conceivable that the haemodialysis treatment itself enhances the greatly increased cardiovascular risk in chronic haemodialysis patients.

Body mass index as indicator of standard of living in developing countries.

OBJECTIVE: To assess the suitability of the body mass index (BMI) as an indicator of standard of living in developing countries. DESIGN, SETTING AND SUBJECTS: The analysis is based on data collected in the first two rounds of the Ghana Living Standards Survey, held in 1987/88 (GLSS-I) and 1988/89 (GLSS-II). The dataset provides information on a wide range of socio-economic variables, at the individual, the household and the community level, including the height and weight data of approximately 9000 adults in the 20-65 y age bracket. METHOD: Bivariate analysis was used to assess, at the individual level and at the level of population groups, the relationships between adult Body Mass Index and selected household characteristics such as income and expenditure, years of schooling of head of household, access to services, quality of housing, and nutritional status of children. Through multiple regression, indicative estimates have been derived of the effects of these variables on adult BMI. For comparison, the same relationships were investigated for weight and height. RESULTS AND CONCLUSION: At the individual level, BMI shows a significantly positive relation with the various socio-economic indicators of living standard, though the correlation coefficients indicate a poor fit. However, at the level of population groups, The relationship between BMI and other characteristics of socio-economic development is strong with a correlation coefficient of 0.86 between mean BMI and mean per capita expenditures of 12 population groups in Ghana, presumed to be at different levels of standard of living. The relationships between weight and the various socioeconomic characteristics were comparable to those for BMI, while height was poorly correlated with the selected household variables. Result suggest that in low-income countries, information on adult BMI (mean and distribution) can be used for assessing differences in standards of living between population groups or for monitoring changes over time.

Cytokine profiles during clinical high-flux dialysis: no evidence for cytokine generation by circulating monocytes.

Secretion of cytokines by monocytes has been implicated in the pathogenesis of dialysis-related morbidity. Cytokine generation is presumed to take place in two steps: induction of mRNA transcription for cytokines by C5a and direct membrane contact, followed by lipopolysaccharide (LPS)-induced translation of mRNA (priming/second signal theory, Kidney Int 37: 85-93, 1990). However, the in vitro conditions on which this theory was based differed markedly from clinical dialysis. To test this postulate for routine hemodialysis, 13 patients were studied cross-over with high-flux cuprammonium (CU), cellulose triacetate (CTA), and polysulfon dialyzers, using standard bicarbonate dialysate, as well as CTA with filtered dialysate (fCTA). Besides leukocytes, C3a, C5a, and limulus amebocyte lysate reactivity, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-1RA, soluble TNF receptors, and IL-1 beta mRNA were assessed. Only during dialysis with CU did C5a increase significantly (561 to 8185 ng/ml, P < 0.001). Endotoxin content of standard bicarbonate was higher than filtered dialysate (median, 24.3 and < 5 pg/ml respectively, P = 0.002), whereas limulus amebocyte lysate reactivity was not detected in the blood, except in the case of CU. TNF-alpha levels were elevated before, and remained stable during, dialysis, independent of the modality used. IL-1 beta, IL-6, and mRNA coding for IL-1 beta could not be demonstrated. IL-1RA and soluble TNF receptors (p55/p75) were markedly elevated compared with normal control subjects, but showed no differences between fCTA and CTA. To summarize, no evidence was found for production and release of cytokines by monocytes during clinical high-flux bicarbonate hemodialysis, neither with complement-activating membranes nor with unfiltered dialysate. Therefore, this study sheds some doubt on the relevance of the "priming/second signal" theory for clinical practice. The data presented suggest that reluctance to prescribe the use of high-flux dialyzers, as advocated in many reports, may not be warranted.

Low polymorphonuclear cell degranulation during citrate anticoagulation: a comparison between citrate and heparin dialysis.

INTRODUCTION: Haemodialysis (HD)-induced bio-incompatibility includes alterations in both cellular elements and humoral factors. As far as polymorphonuclear (PMN) cells are concerned, an increase in both adhesion and degranulation has been reported. However, whereas increased PMN adherence and aggregation is highly linked with early transient complement activation, degranulation seems a continuous process, independent from the formation of complement degradation products. In the process of cell activation, including PMN degranulation, divalent cations (Ca2+) appear to play a pivotal role. As regionally administering citrate creates an almost Ca(2+)-free environment within the dialyser, it is tempting to speculate that Ca2+ dependent phenomena of bio-incompatibility, originating within the dialyser, can be attenuated by substituting conventional heparin for citrate. METHODS: Therefore, both anticoagulation modalities were compared in 10 stable patients, undergoing haemodialysis (HD) treatment with cellulose-triacetate membranes (CTA) only. Apart from the intracellular granule products myeloperoxidase (MPO) and lactoferrin (LF), the classical parameters of bio-incompatibility, peripheral blood neutropenia and complement activation, were measured. RESULTS: Analysis of MPO and LF gradients across the dialyser (concentration in efferent line-concentration in afferent line) suggested that degranulation is an early process, that occurs mainly within the extracorporeal circuit. Citrate abolished the release of MPO almost completely, whereas LF release was partially inhibited. Neither neutropenia, nor complement activation could be correlated with the occurrence of degranulation. CONCLUSIONS: HD-induced PMN degranulation seems largely independent from complement activation, but primarily reliant on Ca2+, at least in the case of CTA membranes.

Mechanisms of intra-dialyser granulocyte activation: a sequential dialyser elution study.

INTRODUCTION: During haemodialysis (HD), an early and transient white blood cell (WBC) reduction is noted in the peripheral blood, which has been attributed mainly to the sequestration of polymorphonuclear cells (PMN) in the pulmonary vasculature. However, WBC also adhere to the dialyser, as demonstrated before in an elution study performed after HD. In the present study, we investigated if intradialyser WBC sequestration contributes to the WBC nadir in the blood shortly after the start of HD and whether or not different mechanisms underlie PMN adherence in dialyser and lung. In addition, PMN degranulation was analysed not only in peripheral blood but also in dialyser eluates (DE). SUBJECTS AND METHODS: Dialysers were eluted after 7 1/2 (DE-7 1/2) and 180 (DE-180) min of HD in eight patients. Blood samples were taken before HD (t0), and at t7 1/2 and t180. Besides WBC count and differentiation, PMN adhesion (CD11b and CD62L) and degranulation markers (CD63 and CD66b) were assessed by flow cytometry. RESULTS: In the blood, a WBC fall was noted at t7 1/2 (from 5.8 to 4.8 x 10(9)/l; absolute about 5 x 10(9) cells). DE contained 3.0 x 10(6) cells at t7 1/2, and 57.2 x 10(6) at t180 (P = 0.015). As for CD11b, at t7 1/2 both in the blood and DE an increased expression was observed, as compared to t0 (P = 0.01); CD11b expression in DE-7 1/2 was higher than in DE-180 (P = 0.025). In contrast, CD62L showed downregulation only in DE both at t7 1/2 (mean fluorescence intensity (MFI) PB 4172 and DE-7 1/2 2353, P = 0.01), and at t180 (MFI 794, P = 0.03 versus DE-7 1/2), when compared to blood at t0. As for degranulation markers, an increase was observed in blood at t7 1/2 (MFI CD63 from 357 to 506, P = 0.02; CD66b from 507 to 794, P = 0.001), in comparison with t0. Eluted PMN at t7 1/2 showed a higher expression of CD63 than PMN in blood at t7 1/2 and DE-180 (MFI in DE-7 1/2 1280 and blood 506, P = 0.003). The expression of CD66b was increased in DE-7 1/2 (MFI 1803 versus blood 794, P = 0.01), and even more in DE-180 (MFI 2763, P = 0.002), when compared to blood. CONCLUSIONS: From these data it is concluded first, that intradialyser PMN sequestration does not contribute markedly to the WBC nadir in the circulation. Second, intradialyser PMN trapping appears to result primarily from non-adhesion-molecule-mediated factors, as indicated by an increased expression of CD11b at t7 1/2 on eluted PMN associated with low cell numbers in DE, and normalized CD11b expression at t180 associated with considerably higher cell numbers in DE. Third, HD-induced degranulation seems to be a complex phenomenon. After a rapid transient onset, characterized by an early upregulation of CD63 and CD66b on PMN leaving the dialyser, degranulation continues within the device as indicated by an additional rise in the expression of CD66b on PMN in DE-180.