Leukopenia and hypoxemia. Unrelated effects of hemodialysis.

Hemodialysis-induced hypoxemia has been attributed to membrane-related complement activation leading to pulmonary leukostasis and to hypoventilation secondary to carbon dioxide losses via the dialyzer. We have separately assessed the role of membrane- and dialysis-related factors by using different dialyzers and sequential ultrafiltration and hemodialysis with first-use cellulose dialyzers produced both leukopenia and hypoxemia. With reused cellulose and polyacrylonitrile dialyzers, hypoxemia still occurred, but without leukopenia. Ultrafiltration produced leukopenia and no changes in Pao2; during the subsequent hemodialysis, hypoxemia developed as the leukocyte count increased by 50%. Our data indicate that leukopenia and hypoxemia are unrelated effects of hemodialysis, and favor hypoventilation as the major determinant of hypoxemia during hemodialysis.     

Gas exchange during dialysis: Contrasting mechanisms contributing to comparable alterations with acetate and bicarbonate buffers

Although arterial hypoxemia during hemodialysis is common and may contribute to dialysis morbidity, the mechanisms responsible remain uncertain. Additionally, controversy exists as to whether bicarbonate dialysate produces less hypoxemia than acetate dialysate. The short- and long-term effects of acetate dialysate and bicarbonate dialysate on gas exchange were compared in eight stable patients undergoing dialysis using a closed, proportioning system and a double-blind, crossover study design. Dialysate was sampled immediately proximal and distal to the dialyzer to determine its contribution to total carbon dioxide elimination. Ventilatory parameters and blood gas values were measured before dialysis, at one hour, and after dialysis. Arterial oxygen tension fell significantly and comparably at one hour with both dialysates, whereas the alveolar-arterial oxygen gradient increased only slightly. Despite hypoxemia, minute ventilation decreased by 4 to 18 percent, and arterial carbon dioxide tension was unchanged. Although total carbon dioxide elimination was unchanged in all groups, there was a significant decrease in lung total carbon dioxide elimination with acetate dialysate of 9.23 ± 2.69 to 7.74 ± 1.57 mmol per minute on Day 1 (mean ± SD, p < 0.025) concomitant with a loss of total carbon dioxide into the bath of 2.04 ± 0.20 mmol per minute, resulting in a significant reduction in respiratory quotient (0.92 ± 0.07 to 0.75 ± 0.05, p < 0.01). In contrast, there was a gain of total carbon dioxide into the blood of 1.64 ± 0.45 mmol per minute with bicarbonate dialysate, which resulted in an increased pH at one hour compared with acetate dialysate (7.39 ± 0.04 versus 7.35 ± 0.03, p < 0.05). Hypoxemia persisted after dialysis in all groups and was associated with an increased alveolar-arterial oxygen gradient in three of the four groups. It is concluded that transitory hypoventilation contributes to comparable hypoxemia with both acetate and bicarbonate dialysates by different mechanisms. With acetate dialysate, there is a decrease in carbon dioxide load to the lungs, whereas with bicarbonate dialysate, the mechanism responsible appears to be a suppression of respiratory drive resulting from a gain of bicarbonate from the dialysate. Additionally, neither dialysate prevents post-dialysis hypoxemia, which is associated with an increased alveolar-arterial oxygen gradient resulting from a mechanism that remains to be elucidated.     

Effect of hemodialysis on contact group of coagulation factors,platelets, and leukocytes

Earlier reports have suggested possible activation and consumption of factor XII during hemodialysis. To investigate this possibility, a series of in vivo and in vitro experiments were conducted using different dialysis membranes and two different dialysates (acetate and bicarbonate). Factors XII and XI activities, factor XII concentration, and high-molecular-weight kininogen were measured. In addition, platelet count, white blood cell count, and hematocrit were monitored. Contrary to the previous reports, no discernible consumption of factor XII, factor XI, or high-molecular-weight kininogen was found irrespective of the type of membrane or the composition of the dialysate used. Transient leukopenia was noted with cellulosic membranes, whereas none occurred with polyachrylonitrile dialyzers. The composition of dialysate did not affect the white blood cell count during dialysis.     

Measurement of backfiltration rates during hemodialysis with highly permeable membranes.

A method for determining local transmembrane fluid movement in a commercial hemodialyzer at low dialysate flow rates by measuring changes along the dialyzer length in the local concentration of a marker macromolecule added to the dialysis solution has been developed. The method was evaluated in vitro at zero net ultrafiltration using dialyzers containing polysulfone (n = 4) and cuprophane (n = 3) membranes. The local concentration of the marker macromolecule along the dialyzer length was higher than the input dialysate concentration only during experiments with dialyzers containing polysulfone membranes. These observations provide direct empirical evidence that fluid movement in the dialysate to blood direction, i.e., backfiltration, occurs during hemodialysis with this highly permeable membrane. Net rates of backfiltration for the dialyzer containing polysulfone membrane were also calculated from changes in the local concentration of the marker macromolecule and mass balance considerations. The calculated backfiltration rates increased with increasing blood flow rate and trended upward with increasing dialysate flow rate. The described methodology provides a novel approach for the further characterization of fluid and solute transport during hemodialysis with highly permeable membranes.     

A model for evening home hemodialysis

In an effort to better rehabilitate patients on home dialysis by shortening the duration of effective dialysis and thereby permitting evening hemodialysis, the simultaneous use of two hollow fiber artificial kidneys (HFAK) was evaluated. The clearances of urea, creatinine, uric acid, phosphate, iothalamate and cyanocobalamin were substantially higher than those obtained with any available single dialyzer. These clearances also were significantly enhanced by use of the single pass dialysate delivery system as compared to the recirculating single pass system. The clearances were comparable whether the blood flow through the two HFAK was in parallel or in series. Reuse of the HFAK was feasible, thus minimizing any economic disadvantage of the system. In eight patients, who have used the system at home for 9 to 12 hours per week for up to 6 months, weight, blood pressure, serum chemistries and motor nerve conduction have remained stable. This shorter dialysis with the double HFAK system allows for evening dialysis, thus freeing daytime hours for productive activity and nighttime for sleep.     

When good water goes bad: how it happens, clinical consequences and possible solutions

Dialysis fluid produced by state-of-the-art water preparation and distribution is contaminated with gram-negative bacteria and cytokine-inducing substances (CIS) derived from these microorganisms. The presence of a biofilm increases the risk of continuous contamination of dialysis fluid. Depending on the type of dialyzer membrane (cellulosic vs. synthetic) and the mode of dialysis (low flux vs. high flux with backfiltration), CIS may penetrate intact dialyzer membranes, induce cytokine production in the patient's blood and contribute to chronic inflammation associated with long-term hemodialysis therapy. Measures to improve the microbiological quality of dialysis fluid are: (1) the awareness of the problem and regular testing of dialysate samples using adequate methods; (2) disinfection of the entire water preparation and distribution system on a regular basis, replacement of biofilm-containing tubings, and (3) installation of ultrafilters in the dialysate circuit in particular when high-flux hemodialysis modalities are performed.     

Evaluation of dialyzer jacket structure and hollow-fiber dialysis membranes to achieve high dialysis performance

The objective of this study was to determine the optimum dialyzer jacket structure and hollow-fiber dialysis membrane, both of which are indispensable factors for achieving high dialysis performance, by clarifying the relationship between the dialysis performance and the flow of dialysate and blood in a hollow-fiber dialyzer. We evaluated the clearance, dialysate, and blood flow for four commercially available hollow-fiber dialyzers, namely, the APS-15S, APS-15SA, TS-1.6UL, and CX-1.6U. To evaluate dialysate and blood flow, we measured the residence-time distribution of dialysate and blood flow of these dialyzers by the pulse-response method. We also determined the clearances of urea, creatinine, vitamin B(12), and lysozyme to evaluate the dialysis performance of these dialyzers. While the baffle and taper structures allow effective supply of dialysate into the dialyzer jacket, the hollow-fiber shape, inner diameter, and packing density significantly influence the dialysate flow. In dialyzers with long taper-holding slits, the slit area is a key design parameter for achieving optimum dialysate flow. Similarly, the blood flow is significantly influenced by the structure of the inflowing and outflowing blood ports at the header of a dialyzer, and the shape and inner diameter of the hollow fibers. Hollow fibers with smaller inner diameters cause an increase in blood pressure, which causes blood to enter the hollow fibers more easily. The hollow-fiber shape hardly affects the blood flow. While improved dialysate and blood flow cause higher clearance of low molecular-weight substances, higher membrane area and pure-water permeability accelerate internal filtration, thereby causing an increase in the clearance of large molecular-weight substances.     

Preliminary report on complement activating potential of polycarbonate membrane

Clinical as well as laboratory studies have been employed to assess the complement activating potential of polycarbonate membrane hemodialyzers. Blood samples from a group of patients undergoing sequential maintenance hemodialysis with cuprophane, polyacrylonitrile and polycarbonate devices were evaluated to define plasma levels of C3a antigen and leukocyte counts during the initial phases of hemodialysis. While polyacrylonitrile dialyzers did not activate complement to a significant extent, we did observe transient elevations in the plasma concentration of C3a and corresponding diminutions in the granulocyte counts of patients dialyzed with both cuprophane and polycarbonate dialyzers. However, polycarbonate devices appeared to activate complement to a lesser degree than cellulosic dialyzers. Laboratory evaluation of these three different types of dialyzers also provided evidence that polycarbonate membranes did not appear to activate human complement as readily as cuprophane. These observations suggest that polycarbonate membranes display complement-related biocompatibility properties that are intermediate between those of cuprophane and polyacrylonitrile.     

血液净化技术对尿毒症患者血浆瘦素、神经肽Y的影响

目的　研究血液净化技术对血浆瘦素、神经肽 Y(NPY)的影响 ,探讨改善尿毒症营养不良的有效措施。方法　本文尿毒症患者 6 9例 ,根据所采用的血液净化技术分为 3组 :低通量纤维素膜透析组 (A组 ) 32例 ,低通量血仿膜 F6透析组 (B组 ) 2 1例 ,F6 0高通量血滤器透析滤过并血液透析组 (C组 ) 16例。另选择 18例健康查体者作为对照组。利用放射免疫法测定患者透析前、后及对照组空腹静脉血的瘦素及 NPY水平。结果　三组瘦素与 NPY水平透析前明显高于对照组 (P<0 .0 1) ;透析后 A、B组瘦素、NPY水平未降低 ,C组瘦素水平明显降低 (P<0 .0 5 ) ,但 NPY无显著变化。结论　尿毒症患者存在高瘦素及 NPY血症 ,二者无相关性 ,都不能通过单纯血液透析清除。利用高通量血滤器进行血液滤过有助于增加瘦素的清除率 ,改善患者营养状态。     

Alterations in hemostatic parameters during hemodialysis with dialyzers of different membrane composition and flow design. Platelet activation and factor VIII-related von Willebrand factor during hemodialysis

The effect of dialyzer membrane and design on hemostatic parameters during hemodialysis were evaluated in a prospective controlled study. This study demonstrated that hemodialysis is associated with significant platelet activation and loss, which are influenced by both dialyzer configuration and membrane composition. In addition, use of the cuprophan membrane is associated with greater perturbations of the vascular endothelium, as reflected in changes in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha concentrations not seen with the polyacrylonitrile membrane. Of the dialyzers studied, the polyacrylonitrile membrane in a hollow-fiber configuration appears to minimize platelet loss and activation, and to minimize increases in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha.     

Controlled oxygen administration in acute respiratory failure in chronic obstructive pulmonary disease: A reappraisal

Controlled oxygen therapy may aggravate carbon dioxide retention during acute exacerbations of chronic obstructive pulmonary disease (COPD). Of 50 consecutive patients with COPD and acute respiratory failure, 13 required intubation because of carbon dioxide narcosis. With discriminant analysis of their arterial oxygen tension (PaO₂) and pH on admission, a diagram separated patients into those at high risk and those at low risk for carbon dioxide narcosis. This diagram was then used to predict carbon dioxide narcosis in 73 patients with COPD and acute respiratory failure who were treated with controlled oxygen. In 16 of these patients carbon dioxide narcosis developed. Thirteen (81 per cent) were predicted by the diagram to be at high risk for this complication. Only two (4 per cent) patients judged by the diagram to be at low risk for carbon dioxide narcosis required mechanical ventilation. Utilizing an oxygen tension (PO₂), carbon dioxide tension (PCO₂) diagram a patient's ventilatory response was compared to that of ambulatory patients with COPD. These data suggest that hypoxemia and acidosis are more discriminatory for “carbon dioxide narcosis” than hypercapnia.     

Cardiovascular function and arterial blood gases during sham dialysis in healthy man

Cardiovascular function and alveolar gas exchange were studied in healthy subjects undergoing sham dialysis (SHD)--i.e. the circulation of blood through a cuprophane dialyzer with the dialysate compartment closed to avoid diffusion and convective transport of fluid and solutes. The blood-membrane contact induced complement activation (rise in C3d) and transient leukopenia, as described during clinical hemodialysis. PaO2, PaCO2 and calculated oxygen uptake remained unchanged. Heart rate, cardiac index (thermodilution), systemic vascular resistance index and brachial and pulmonary arterial blood pressures did not change significantly during 150 min of SHD (n = 8). In 12 subjects, in whom more frequent measurements were made during the first 30 min of SHD, pulmonary arterial systolic and diastolic blood pressures decreased significantly while the dialyzer and the tubing set filled with blood, and pulmonary arterial mean blood pressure did not change significantly. Pulmonary capillary wedge pressure fell during the filling phase, but did not change significantly during SHD; pulmonary vascular resistance index remained unchanged. We conclude that in nonuremic subjects sham dialysis with a cuprophane dialyzer does not result in hypoxemia, pulmonary vascular constriction and pulmonary hypertension, in spite of complement activation and marked leukopenia.     

Biocompatibility aspects of cellophane, cellulose acetate, polyacrylonitrile, polysulfone and polycarbonate hemodialyzers

The biocompatibility of cuprammonium rayon (Cu), cellulose acetate, polysulfone (Ps) and polyacrylonitrile hollow-fiber dialyzers and a polycarbonate-polyether flat plate dialyzer has been investigated. The Cu dialyzer resulted in more complement activation and a greater degree of leukopenia than the others, while the Ps hollow-fiber dialyzer appeared to be the most biocompatible of the membrane equipment in this study. These results were confirmed by in vitro evaluations and microscopic examinations of the different dialyzers.     

Biocompatibility parameters of different dialysis membranes assessed during systemic inflammation

BACKGROUND: We explored whether biocompatible dialyzer membranes modulate the inflammatory response during blood contact in patients with systemic inflammation. METHODS: 15 patients with end-stage renal disease and systemic inflammation (mean serum C-reactive protein 86 +/- 4 mg/l) were randomly treated with Cuprophan (CU), polyamide (PA) and vitamin-E coated (VEC) membrane-based dialyzers. RESULTS: Changes in blood pressure, capillary blood oxygen saturation and differential blood counts during the hemodialysis session were not significantly different between the three dialyzers. Baseline blood levels of activated circulating complement (C3a) were more than 100 times above normal, and unlike expected they decreased during hemodialysis treatments (CU: from 7,389 +/- 783 to 5,423 +/- 761 ng/ml; PA: from 7,379 +/- 980 to 5,690 +/- 714 ng/ml; VEC: from 7.377 +/- 714 to 5,360 +/- 1,005 ng/ml; all n.s.). No significant differences between treatments were found with respect to changes in blood concentrations of TNF-alpha, interleukin-6 and interleukin-1 receptor antagonist as well as ICAM-1 (CU: from 451 +/- 41 to 477 +/- 41 ng/ml; PA: from 437 +/- 42 to 449 +/- 40 ng/ml; VEC: from 461 +/- 43 to 460 +/- 47 ng/ml). Furthermore, generation of reactive oxygen species by mononuclear blood cells was comparable during hemodialysis with the CU, PA and VEC dialyzer. CONCLUSION: The choice of dialyzer membrane material does not affect most aspects of biocompatibility when patients have significant systemic inflammation. This confounding variable should be taken into account in studies exploring the effects of biocompatible dialyzer membranes.     

Vitamin E-coated dialyzer membranes downregulate expression of monocyte adhesion and co-stimulatory molecules

BACKGROUND: In patients on chronic hemodialysis leukocyte activation has been related to the impaired function of the immune system. In this study we investigated if the vitamin E-coated dialyzer membrane could reduce monocyte activation thereby improving cellular immunity. METHODS: This hypothesis was tested in a prospective crossover trial in which 14 stable hemodialysis patients were switched from the baseline hemophane dialyzer to a vitamin E-coated and thereafter a polysulphone dialyzer membrane or vice versa. RESULTS: Monocyte MHC class I, CD54 and ICAM-1 expression was significantly downregulated when a vitamin E-coated or polysulphone dialyzer was used. The use of a vitamin E membrane specifically decreased monocyte CD40 and CD86 expression. Lectin induced T cell proliferation increased with the use of the vitamin E-coated membrane as compared to polysulphone and hemophane dialyzers. CONCLUSION: Vitamin E-coated dialyzers induced a less-activated phenotype of monocytes and may improve cellular immunity.     

Changes in squamous cell carcinoma-related antigen levels before and after hemodialysis in relation to the model of dialyzer employed

OBJECTIVE: Although tumor marker levels in blood become elevated after hemodialysis as a result of the amount of fluid removed, serum squamous cell carcinoma-related antigen (SCC) levels have not been always reported to increase after hemodialysis. The purpose of this report is to determine whether there is a difference between the change of serum SCC levels before and after hemodialysis according to the model of dialyzer employed. PATIENTS AND METHODS: In ninety-four patients on hemodialysis (50 cases of diabetic nephropathy and 44 cases of glomerulonephritis), we examined serum SCC levels before and after hemodialysis. RESULTS: There was no overall difference between SCC levels before and after hemodialysis (3.2+/-1.5 ng/ml vs 3.3+/-1.7 ng/ml, p=0.2381). In patients treated with a cellulosic type membrane dialyzer (n=73), SCC levels after hemodialysis were higher than those before hemodialysis (3.7+/-1.7 ng/ml vs 3.5+/-1.5 ng/ml, p=0.0495). In patients treated with a synthetic type membrane (n=21), SCC levels after hemodialysis decreased when compared to those before hemodialysis (1.9+/-0.7 ng/ml vs 2.2+/-0.8 ng/ml, p=0.0018) and in all patients, the SCC levels after hemodialysis were lower than, or equal to, those before hemodialysis. CONCLUSION: The results suggest that the decline in serum SCC levels during hemodialysis treated with synthetic type membrane of dialyzers, concealed the increased SCC levels in hemoconcentration.     

Accumulation of bisphenol A in hemodialysis patients

Bisphenol A [BPA, 2,2-bis(4-hydoxyphenyl)propane], an industrial chemical used in the production of polycarbonate, epoxide resin, and polyarylate, is considered to be an endocrine-disrupting chemical. BPA may be present in some hollow-fiber dialyzers used in hemodialysis. In this study, we tested the amounts of BPA eluted from various hollow fibers. Furthermore, we measured the BPA concentration in the sera of 22 renal disease predialysis patients, as well as 15 patients who were receiving hemodialysis, to see if there is BPA accumulation in these patients. The elution test of BPA showed that a much larger amount of BPA was eluted from polysulfone (PS), and polyester-polymeralloy hollow fibers. Among renal disease patients who had not undergone hemodialysis, the serum BPA concentration increased as the renal function deteriorated, showing a significant negative association. In a crossover test between PS and cellulose (Ce) dialyzers, the predialysis serum BPA concentration of PS dialyzer users decreased after changing to a Ce dialyzer, and the serum BPA increased again after switching back to PS dialyzers. In patients who were using PS dialyzers, the BPA level significantly increased after a dialysis session. However, in the Ce dialyzer users, the BPA level decreased. Since accumulation of BPA could affect the endocrine or metabolic system of the human body, it is important to perform further investigations on dialysis patients.     

Pulmonary function in asymptomatic adolescents with idiopathic scoliosis.

Pulmonary function studies were performed in 28 asymptomatic adolescents with idiopathic scoliosis. Tests included spirometry, flow volume curve, measurements of inspired gas distribution, diffusing capacity, closing volume, ventilatory response to carbon dioxide, and arterial blood gas analysis. In addition to the well-known decreases in lung volumes, a reduction in diffusing capacity, arterial oxygen tension, and ventilatory response to carbon dioxide were also documented. Significant correlations existed between the severity of the spinal curvature and the decrease in lung volumes. A significant correlation was also found between the degree of hypoxemia and the reduction in the diffusing capacity, suggesting that a low diffusing could be the cause of the observed arterial hypoxemia.     

A Retrospective Study on Erythropoiesis Stimulating Agent Dose Reducing Potential of an Anti‐Platelet Activation Membrane Dialyzer in Hemodialysis Patients

Our previous small‐scale trial demonstrated an erythropoiesis stimulating agent (ESA)‐sparing potential of the TORAYLIGHT NV (NV) dialyzer in hemodialysis patients with high interleukin‐6 levels. We now retrospectively explored this ESA‐sparing potential of the NV dialyzer in 122 and 129 prevalent dialysis patients who were on the NV and conventional polysulfone (PS) dialyzers, respectively, for 12 months. ESA resistance index (ERI) increased with the PS dialyzers whereas neither ERI nor ESA dose changed with the NV dialyzer. Analyses of baseline ERI or ESA dose‐based subgroups revealed a decrease in ERI and ESA dose with the NV dialyzer in patients with a baseline ERI ≥12 IU·dL/week·kg·g Hb (P < 0.05) and in those with a baseline ESA dose >6000 IU/week (P < 0.001), respectively. Neither ERI nor ESA dose improved in the corresponding subgroups on the PS dialyzers. These findings suggest that NV dialyzer can improve ESA responsiveness in hemodialysis patients with advanced ESA resistance.