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J Himmelfarb

Publications and source records attributed to J Himmelfarb.

At least 37 records · Page 2Linked to original sources
PubMed1998

Change in access blood flow over time predicts vascular access thrombosis.

BACKGROUND: Vascular access thrombosis accounts for at least $1 billion dollars in annual expenses and 25% of hospitalizations for chronic hemodialysis patients. Low vascular access blood flow (less than 800 ml/min) has been shown to modestly increase the relative risk for thrombosis in the subsequent three months. In this study, it is hypothesized that a time-dependent decrease in vascular access blood flow may be more predictive of subsequent thrombosis especially in vascular accesses with flows more than 800 ml/min, since it would indicate the development of a critical outlet stenosis in the graft. METHODS: Ninety-five accesses in 91 CHD patients were prospectively followed over 18 months. Vascular access blood flow was measured every six months by the ultrasound dilution technique. Thrombotic events were recorded during the three study periods. RESULTS: A total of 34 thrombotic events in 95 accesses were documented through the total study duration. Accesses that thrombosed had a 22% decrease in vascular access blood flow during the first observation period and a further 41% decrease during the second observation period as compared to 4% drop and 15% increase during the first and second observation periods, respectively, for accesses that did not thrombose. There was an estimated 13.6-fold (95%, confidence interval 2.68 to 69.16) increase in the relative risk of thrombosis for accesses with more than 35% decrease in vascular access blood flow compared to those accesses with no change in blood flow. There was no statistical difference in the average vascular access blood flow of all patients over the study period. CONCLUSIONS: Accesses that show a large (>15%) decrement in vascular access blood flow are associated with a high risk of thrombosis. Serial measurements of vascular access blood flow predict access thrombosis.

Adult↗
PubMed1998

Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients.

A bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P < 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P < 0.05) or peritoneal dialysis patients (62+/-2; P < 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.

Blood Platelets↗
PubMed1998

Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study.

Despite several decades of clinical experience, the mortality rate for patients with acute renal failure (ARF) requiring dialysis remains high, and the evaluation of the patients prognosis has been difficult. To date, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been used more frequently for prediction in studies of ARF than any other scoring system, but has not been prospectively validated in controlled multicenter studies of this entity. In a multicenter, prospective, controlled trial evaluating the use of biocompatible hemodialysis membranes (BCMs) in patients with ARF, we evaluated the extent to which the APACHE II scoring system, based on the physiological variables in the 24 hours before the onset of dialysis and the presence or absence of oliguria, is predictive of outcome. Analysis of survival and recovery of renal function for the 153 patients treated in this study show that APACHE II scores are predictive both of survival and recovery of renal function, whether analyzed separately by type of dialysis membrane used (BCM or bioincompatible [BICM]) or for both groups combined (all P < 0.01). There was no evidence of a significant center effect or interaction of APACHE II score with dialysis membrane in our study. After adjusting for the APACHE II score, there was a positive effect of the BCM on both probability of survival (P < 0.05) and recovery of renal function (P < 0.01). In patients dialyzed with BCMs, oliguria at onset of dialysis had an adverse effect on both survival and recovery of renal function (both P < 0.01). Receiver operator curves (ROCs) using APACHE II score and the use of BCMs in nonoliguric patients yielded a statistically significant improvement versus the use of APACHE II score alone in the area under the curve (AUC) for survival (0.747 to 0.801; P < 0.05) and recovery of renal function (0.712 to 0.775; P < 0.05). We conclude that the use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival and recovery of renal function. The use of the APACHE II score measured at the time of dialysis initiation, especially when modified by the presence or absence of oliguria, should help in predicting outcome when evaluating interventions for patients with ARF.

APACHE↗
PubMed1998

A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis.

The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis.

APACHE↗
PubMed1997

Aspirin enhances platelet-derived growth factor-induced vascular smooth muscle cell proliferation.

PURPOSE: Aspirin is frequently used after vascular reconstruction to pharmacologically prevent graft occlusion and to suppress the development of myointimal hyperplasia in vascular surgery, but its efficacy is controversial. The purpose of this study was to examine the direct effects of aspirin on platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell (SMC) proliferation. METHODS: Human aortic SMCs were grown to confluence in 96 well plates. 3 x 10(-5) mol/L aspirin was added 24 hours previously and PDGF 10 ng/ml at the beginning of each experiment. Cell proliferation at 48 hours was determined using tritiated thymidine uptake. Supernatant 12-L-hydroxy 5,8,10,14-eicosatetraenoic acid (12-HETE) and prostaglandin E2 (PGE2) were measured by competitive enzyme immunoassay. RESULTS: Aspirin did not change vascular SMC proliferation rates relative to controls (4665 +/- 181 counts per minute [CPM] vs 4749 +/- 155 CPM). However, aspirin pretreatment of PDGF-stimulated vascular SMCs increased proliferation (9408 +/- 237 CPM vs 7283 +/- 283 CPM; p < 0.001). 5,8,10,14-eicosatriynoic acid, a 12-lipoxygenase inhibitor, decreased basal (2037 +/- 181 CPM vs 2306 +/- 158 CPM; p < 0.05) and PDGF-stimulated vascular SMC proliferation (4909 +/- 1089 CPM vs 4310 +/- 1022 CPM; p < 0.001). Aspirin increased supernatant 12-HETE levels and decreased PGE2 levels in both basal and PDGF-stimulated cell cultures. CONCLUSIONS: Aspirin enhances PDGF-stimulated vascular SMC proliferation. The effects of aspirin on vascular SMC proliferation may be mediated by changes in vascular SMC arachidonic acid metabolism.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1997

Increased reticulated platelets in dialysis patients.

The purpose of this study was to measure the percent reticulated platelets and platelet counts in patients on chronic hemodialysis, peritoneal dialysis and normal volunteers. The relationship between the percent reticulated platelets and the platelet count can then be used to determine the rate of platelet turnover. Platelet rich plasma was obtained, platelets were fixed and incubated with thiazole orange and analyzed for the percent reticulated platelets by flow cytometry. Normal controls had a mean of 2.77 +/- 0.17% reticulated platelets while peritoneal dialysis patients had a mean percent reticulated platelets of 6.92 +/- 0.68 (P < 0.00001). Chronic hemodialysis patients had a mean percent reticulated platelets of 8.21 +/- 0.36 (P < 0.00001 vs. normal controls and P = 0.05 vs. peritoneal dialysis patients). Platelet counts did not differ significantly among the three groups. The identity of reticulated platelets was confirmed in experiments measuring platelet specific glycoproteins, experiments using RNase, and in mixing experiments with normal and uremic platelets and plasma. We conclude that dialysis patients have a marked increase in circulating reticulated platelets compared to normal controls, indicating accelerated platelet turnover. Increased platelet activation and turnover may contribute to the qualitative platelet dysfunction observed in dialysis patients.

Blood Platelet Disorders↗
PubMed1997

Predictive measures of vascular access thrombosis: a prospective study.

Malfunction of permanent vascular accesses remains a cause of frequent and costly morbidity in patients receiving chronic hemodialysis (CHD). Several recommendations for routine monitoring of these permanent vascular accesses for incipient failure have been proposed. In this study, multiple indicators of incipient vascular access dysfunction, including "venous" and "arterial" pressures at serial blood flows (200 ml/min, 300 ml/min, and 400 ml/min), percent urea recirculation, Doppler ultrasound, and access blood flow by ultrasound dilution technique were simultaneously evaluated in a total of 220 vascular accesses in 170 chronic hemodialysis patients in two separate study periods (6 months apart). The rate of thrombosis was determined within the subsequent 12 weeks of each study period to assess the short-term predictive power of access thrombosis. During the period of follow-up, there were 34 thrombotic events in 172 polytetrafluoroethylene (PTFE) grafts and only one thrombotic event in 48 arterio-venous fistulas (AVF). Therefore, the statistical analysis was limited to the PTFE grafts. When grafts with thromboses were compared to those without thrombosis by univariate analysis, access blood flow measured either by ultrasound dilution technique (875 +/- 426 ml/min with thrombosis vs. 1193 +/- 677 ml/min without thrombosis, P = 0.001) or by Doppler ultrasound (762 +/- 420 ml/min with thrombosis vs. 1171 +/- 657 ml/min without thrombosis, P = 0.001) were significantly different in the two groups. There was good correlation (r = 0.79, P = 0.0001) between the blood flows determined by both techniques. The grade of stenosis determined by ultrasound was also a statistically significant predictor (P = 0.02). "Venous" and "arterial" pressures were numerically similar and were not statistically different between the accesses that did and those that did not thrombose. When multivariate analysis was used, there was a significantly increased risk of thrombosis only with decreasing access blood flow determined by ultrasound dilution techniques after adjusting for other confounding variables. When the average blood flow of all grafts (1134 ml/min) is considered as the reference access blood flow (relative risk of 1.0), the relative risk of a PTFE thrombotic event within the subsequent 12 weeks was 1.23 at a blood flow 950 ml/min, 1.67 at a blood flow of 650 ml/min and to 2.39 at a blood flow of 300 ml/min. In summary, access blood flow measured by either Dilution or Doppler is a reliable indicator of subsequent short-term thrombosis risk. Other proposed methods of evaluating access dysfunction were not useful in our patients. If simple to use, cost-effective devices to measure dialysis access blood flow become readily available, the measurement of access blood flow will likely become the method of choice for screening of PTFE vascular access dysfunction in hemodialysis patients.

Aged↗
PubMed1997

Dipyridamole inhibits PDGF- and bFGF-induced vascular smooth muscle cell proliferation.

Dipyridamole is the only pharmacologic agent demonstrated to reduce polytetrafluoroethylene (PTFE) graft occlusion in hemodialysis patients. However, the mechanism of action of dipyridamole in preventing graft occlusion is unknown. The purpose of this study was to examine the direct effects of dipyridamole on both platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF)-induced vascular smooth muscle cell (VSMC) proliferation. Human aortic smooth muscle cells were grown to confluence in 96 well plates. A total of 5 x 10(-6) molar dipyridamole, PDGF 10 ng/ml, or bFGF 10 ng/ml were added to appropriate wells at the start of each experiment. Cell proliferation at 48 hours was determined using tritiated thymidine uptake. Intracellular cyclic AMP (cAMP) was measured using a competitive enzyme immunoassay. Treatment of VSMC with 5 microM dipyridamole dramatically reduced basal proliferation rates compared to controls [5229 +/- 1131 counts per minute (CPM) versus 387 +/- 68 CPM, P < 0.001]. Treatment with dipyridamole also reduced PDGF-stimulated VSMC proliferation (7311 +/- 1655 CPM vs. 593 +/- 110 CPM, P < 0.001) as well as the response to bFGF (5632 +/- 1270 CPM vs. 310 +/- 31 CPM, P < 0.001). Treatment of VSMC with either 5 or 20 microM dipyridamole did not change intracellular cAMP levels. Furthermore, the addition of dibutyryl cAMP to VSMC demonstrated only a modest inhibitory effect on proliferation. We conclude that dipyridamole inhibits both PDGF- and bFGF-stimulated VSMC proliferation. The effects of dipyridamole on VSMC proliferation do not appear to be entirely mediated by changes in intracellular cAMP concentrations. The direct effect of dipyridamole on VSMC proliferation may account for its efficacy in reducing PTFE graft thrombosis in hemodialysis patients.

Aorta↗
PubMed1997

Nutrition in acute renal failure patients.

The care of patients with acute renal failure remains a challenge for the nephrologist, with unacceptably high mortality rates. Among many other contributing factors, protein-calorie malnutrition has been suggested as an important predictor of outcome. Protein-calorie malnutrition is highly prevalent in acute renal failure (ARF) patients, and extensive catabolism is a hallmark of these patients. Hypercatabolism can be related to abnormal protein metabolism as well as be a consequence of renal replacement therapy. Inadequate nutritional supplementation also predisposes acute renal failure patients to poor nutritional status. Although multiple studies have evaluated the effects of aggressive nutritional supplementation to reverse malnutrition and improve the outcome in ARF patients, the complexity of the disease process has precluded obtaining meaningful and clear-cut results from these clinical studies. Nevertheless, there is a great need as well as potential to study the actual importance of nutritional aspects in complicated ARF patients.

Acute Kidney Injury↗
PubMed1997

The use of biocompatible dialysis membranes in acute renal failure.

The interactions between blood and the dialysis membrane, aside from solute clearance, can be referred to as biocompatibility. It has increasingly been recognized that significant side effects may occur as a result of interactions of blood with the dialysis membrane itself. The use of unmodified cellulosic hemodialysis membranes results in potent activation of the alternative pathway of complement, and numerous investigators have now carefully defined the membrane characteristics that contribute to complement activation, adsorption, and clearance. Complement-dependent granulocyte activation during hemodialysis causes neutrophil degranulation and protease release, the production of reactive oxygen species, and modulation of granulocyte cell adhesion molecules. Recently, a number of experimental studies in animal models suggest that complement and granulocyte activation during hemodialysis could contribute to the prolongation of acute renal failure. Based on the hypothesis that hemodialysis with complement and granulocyte-activating membranes could contribute to the prolongation of acute renal failure and increased mortality, several recent prospective randomized clinical trials examining the role of membrane biocompatibility in the treatment of acute renal failure have been reported. Although not unanimous in their conclusions, most studies suggest that hemodialysis with more biocompatible membranes in patients with acute renal failure leads to a more rapid return of renal function and a lower morbidity and mortality. Thus, hemodialysis membrane biocompatibility may be an important contributor to the outcome of patients with acute renal failure who require dialysis.

Acute Kidney Injury↗
PubMed1996

Hemodialysis vascular access: emerging concepts.

Vascular access complications remain a leading cause of morbidity and hospitalization in patients on chronic maintenance hemodialysis. Although arteriovenous fistulas remain the dialysis access of choice, an increasing percentage of patients are dialyzed using synthetic grafts or permanent catheters. The most frequent vascular access complications are the development of stenosis and of thrombosis. In recent years, increasing attention is being paid to screening techniques designed to detect vascular access stenosis prior to thrombosis. Aggressive screening techniques coupled with interventional procedures such as angioplasty may reduce the incidence of graft thrombosis. Once thrombosis has occurred, mechanical or pharmacomechanical thrombolysis in conjunction with angioplasty may be an effective alternative to surgical thrombectomy.

Catheters, Indwelling↗
PubMed1995

Soluble complement receptor 1 inhibits both complement and granulocyte activation during ex vivo hemodialysis.

Hemodialysis with cellulosic membranes results in both complement and granulocyte activation. We investigated the effects of soluble complement receptor 1 (sCR1), a potent complement inhibitor, on both complement and granulocyte activation in an ex vivo model of dialysis. Measurements were made of complement activation (radioimmunoassay for C3a desArg) as well as granulocyte activation (flow cytometric measurements of reactive oxygen species production, granulocyte CD11b/CD18 (MAC-1) expression and CD62L (L-selectin) expression). sCR1 completely abolished the generation of plasma C3a desArg during ex vivo hemodialysis. Without sCR1, C3a desArg levels rose from 968 +/- 373 ng/ml to 4961 +/- 40 ng/ml by the end of the ex vivo procedure (p < 0.001). sCR1 also completely inhibited MAC-1 upregulation and L-selectin shedding from granulocytes during ex vivo hemodialysis. With sCR1 there was still a statistically significant increase in granulocyte reactive oxygen species production (from 2.42 +/- 0.1 fluorescence channels to 6.47 +/- 0.7 fluorescence channels, p < 0.01) but a 50% inhibition when compared with experiments without sCR1 (3.15 +/- 0.5 to 11.2 +/- 1.9, p < 0.01). We conclude that sCR1 completely abolishes complement activation and changes in granulocyte cell adhesion molecules during ex vivo hemodialysis with cellulosic membranes. sCR1 partially inhibits granulocyte reactive oxygen species formation.

Anaphylatoxins↗
PubMed1994

Kt/V, nutritional parameters, serum cortisol, and insulin growth factor-1 levels and patient outcome in hemodialysis.

Despite many technical advances in dialysis care, morbidity and mortality in chronic hemodialysis patients in the United States remains high. In this study, we analyzed the effects of Kt/V, nutritional parameters (serum albumin level, triceps skin-fold thickness, mid-arm muscle circumference, and normalized protein catabolic rate), and predialysis serum cortisol and insulin growth factor-1 levels on predicting morbidity and mortality. The cohort studied consisted of 52 patients recruited from a single outpatient dialysis facility. Cox proportional hazards modeling indicated that only Kt/V predicted subsequent mortality (P = 0.02), while both predialysis cortisol levels (P = 0.03) and Kt/V (P = 0.03) predicted hospitalization. Kaplan-Meier analysis demonstrated that the ability of cortisol levels to predict hospitalization was largely confined to the group with values greater than 22 micrograms/dL predialysis. High serum cortisol levels were correlated with low serum albumin levels and a trend toward low triceps skin-fold thickness and higher normalized protein catabolic rate, suggesting a catabolic state. Both predialysis serum cortisol and insulin growth factor-1 levels were higher than those in age- and sex-matched normal human controls. These results demonstrate the importance role of Kt/V in predicting subsequent hospitalization rates and mortality, and that high predialysis serum cortisol levels correlate with a high hospitalization rate.

Adult↗
PubMed1994

Effects of aprotinin on complement and granulocyte activation during ex vivo hemodialysis.

Hemodialysis with cellulosic membranes results in complement activation, granulocytopenia, and granulocyte activation. To further investigate the relationship between complement activation and granulocyte activation, we developed a model of ex vivo hemodialysis with blood flow, dialysate flow, and dialysate composition similar to in vivo hemodialysis. We used this model to investigate the effects of aprotinin, a potent serine protease inhibitor frequently used as an anti-inflammatory agent during cardiopulmonary bypass surgery, on both complement and granulocyte activation. Seven normal human volunteers were phlebotomized for ex vivo hemodialysis on two occasions each, one with and once without 800,000 kallikrein inhibitor units of aprotinin added to the circuit. Measurements were made of complement activation (radioimmunoassay for C3a desArg and C5a desArg), as well as granulocyte activation (flow cytometric measurements of reactive oxygen species (ROS) production, granulocyte CD11b-CD18 [MAC-1, CR3] expression, and CD62-L [L-selectin] expression). Statistically significant elevations in C3a desArg levels occurred by 10 minutes and reached a maximum of 5,367 +/- 712 ng/mL by 60 minutes after the initiation of ex vivo hemodialysis. Plasma C5a levels were elevated to 236 +/- 32 ng/mL at 60 minutes compared with 45 +/- 15 ng/mL predialysis. Aprotinin was able to significantly inhibit dialysis-induced C3a generation (peak 2,456 +/- 572 ng/mL at 60 minutes) as well as C5a generation (86 +/- 23 ng/mL at 60 minutes). During ex vivo hemodialysis, there was also a significant increase in granulocyte ROS production, MAC-1 upregulation, and L-selectin downregulation. Changes in granulocyte activation were not affected by the administration of aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗
PubMed1994

Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study.

Hemodialysis (HD) vascular access thrombosis remains a major cause of morbidity, accounting for 17.4% of all HD patient hospital admissions in 1986. We initiated this prospective, randomized, double-blind, placebo-controlled, parallel group study to examine if dipyridamole and/or aspirin decreased the rate of thrombosis of expanded polytetrafluoroethylene (ePTFE) grafts in HD patients. Two patient groups were studied: Type I--with a new ePTFE graft; and Type II--with thrombectomy and/or revision of a previously placed ePTFE graft. One hundred and seven patients were followed for 18 months or until the first thrombotic episode. Actuarial analysis of Type I patients showed cumulative thrombosis rates (mean +/- SEM) of 21 +/- 9% on dipyridamole alone, compared with 25 +/- 11% on dipyridamole and aspirin combination, 42 +/- 13% on placebo, and 80 +/- 12% on aspirin alone. The relative risk of thrombosis with dipyridamole was 0.35 (P = 0.02) and that for aspirin was 1.99 (P = 0.18). In Type II patients, the rate of thrombosis was high in all study drug and placebo groups (overall 78% thrombosis) and actuarial analysis was not carried out because of the small number of patients enrolled. We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts. Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts.

Adult↗
PubMed1994

Biocompatibility and risk of infection in haemodialysis patients.

Infection remains a major cause of morbidity and mortality in the dialysis patient. Most of these infections are bacterial and often lead to sepsis. In this review the possible influence of the biocompatibility of the dialysis membrane on the incidence of bacterial infections is discussed. Specifically, the role of the membrane on granulocyte function such as phagocytosis, adhesion, and production of reactive oxygen species is shown to be adversely affected by recurrent exposure to complement-activating membranes. Recent clinical studies also support the notion that dialysis with bioincompatible membranes is associated with a higher incidence of clinical infections than membranes that are more biocompatible.

Biocompatible Materials↗
PubMed1993

Intradialytic granulocyte reactive oxygen species production: a prospective, crossover trial.

By the use of flow cytometric techniques, this prospective, randomized crossover study was designed to analyze intradialytic granulocyte reactive oxygen species (ROS) formation in whole blood with complement-activating and noncomplement-activating hollow fiber membranes. Dialysis with a complement-activating membrane resulted in a 6.5-fold increase in granulocyte hydrogen peroxide production 15 min after dialysis initiation and remained significantly elevated (P < 0.01) through the first 30 min with this membrane in comparison to both predialysis values and simultaneous values with a noncomplement-activating membrane. Further studies demonstrated that blood obtained at 15 min with a complement-activating membrane generated significantly less granulocyte ROS production in response to Staphylococcus aureus incubation than blood obtained either predialysis or at the same time in dialysis with a noncomplement-activating membrane. Both complement-activating and noncomplement-activating dialysis membranes caused slightly decreased granulocyte responsiveness to phorbol myristate acetate. It was concluded that hemodialysis with complement-activating membranes results in increased granulocyte ROS production and decreased responsiveness to S. aureus challenge during the dialysis procedure. These results document the potential role of ROS in hemodialysis-associated pathology and susceptibility to infection.

Adult↗