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Biomedical subjects

N A Hoenich

Publications and source records attributed to N A Hoenich.

At least 19 recordsLinked to original sources
PubMed2002

Is decreased treatment time in hemodialysis patients harmful if solute clearance is maintained?

An association between decreased duration of hemodialysis and increased morbidity and mortality in patients has been suggested. Whether this is due only to decreased solute clearance is unclear. In this prospective randomised study the effect of reducing treatment time whilst maintaining constant solute clearance was examined in fourteen patients. The study lasted for a period of 36 weeks (3x12 week study periods) and used a crossover design. The patients dialysis prescription (KW) was not changed on entering the study and was maintained during short (150 minutes) and long dialysis (240 minutes) by varying blood flow, dialysate flow and dialyzer surface area. The delivered KW was kinetically assessed. Fractional urea clearance was also measured during each treatment period by measurement of urea concentration in spent dialysate and total body water using 3H2O. At the end of each treatment period a full biochemical and hematological profile, nutritional intake and status, 24 h ambulatory blood pressure, nerve conduction studies, and quality of life questionnaire were performed. Within patients the delivered single pool KW was uniform throughout the 3 treatment periods and fractional urea clearance did not vary. However, Kt/W assessed using equilibrated models (Daugardis and Smye) was significantly lower in the short dialysis period. No differences between short and long dialysis sessions were noted in any of the measured variables. Thus, over a 36 week period there is no evidence to suggest that hemodialysis patients are adversely affected by decreased duration of treatment provided that solute clearance is maintained.

Aged↗
PubMed2002

Accuracy and clinical utility of dialysis dose measurement using online ionic dialysance.

BACKGROUND: Statistical associations between urea removal and survival have been described in a number of publications. Urea removal during treatment may be quantified by the delivered dose of dialysis. Methods in clinical use to measure delivered dose are retrospective and reliant on accurate blood sampling. The new generation of single patient proportionating systems incorporate the facility to automatically measure ionic dialysance throughout dialysis. METHODS: In a prospective study on 9 anuric patients with a stable dialysis prescription, we have compared the agreement of the dose of dialysis determined from ionic dialysance (Dt/V) with that derived from equilibriated Kt/V (eKt/V) and Kt/V measured by direct dialysis quantification (Kt/V(DDQ)) using 2 types of hemodialysis membrane (hemophan and low-flux polysulfone). The variability of the delivered dose over a 1-month period was also determined. RESULTS: Ionic dialysance was independent of membrane type. It was comparable to that established for plasma urea water clearance for hemophan but lower for polysulfone (p < 0.001). The mean (+/- SD) delivered dose of dialysis (Dt/V) was similar for both membranes (1.18 +/- 0.15 (hemophan) and 1.18 +/- 0.11 (low-flux polysulfone)). Bland Altman comparisons showed the limits of agreement between Dt/V and Kt/V(DDQ) were +/- 0.17 and for Dt/V compared with eKt/V +/- 0.15. A 1-month measurement of Dt/V demonstrated considerable treatment to treatment variability indicating that delivered dose cannot be considered stable. CONCLUSION: The availability of online measurement of ionic dialysance provides a step towards monitoring dialysis more closely at the time of delivery, and its clinical application will ensure that a more constant dialysis dose is delivered.

Adult↗
PubMed2001

Oxidative stress and inflammation in hemodialysis patients.

Dialysis is associated with an increased generation of oxidants, which play an important part in the development of endothelial dysfunction and atherogenesis. Markers of oxidative stress include F2-isoprostanes and ethane. Measurements in dialysis patients before dialysis showed higher levels of esterified plasma F2-isoprostanes (1.62 +/- 0.73 ng/mL) than in control subjects (0.27 +/- 0.10 ng/mL) (P < 0.001). Furthermore, levels also correlated with high plasma C-reactive protein (CRP) levels (r =.48, P = 0.015). Breath ethane levels for dialysis patients (N = 19) were 6.32 +/- 3.16 pmol/kg-min, in contrast to 3.08 +/- 1.50 pmol/kg-min in control subjects (N = 11, P < 0.005). Analysis to investigate the relationship between CRP levels and outcome indicated that there was a significant difference in mortality rate over a 3-year period between patients with low and high CRP values (P < 0.001). Patients with high CRP (> 16.8 mg/L) levels were more than twice as likely to die as patients with low CRP levels (relative risk [RR] = 2.16; 95% confidence interval [CI], 1.50-3.09). CRP values were a significant predictor of mortality even after controlling for diabetes, albumin, ferritin, and age at commencement of dialysis. The RR for CRP after adjustment was 1.58 (95% CI, 1.06-2.34, P = 0.024). There were no significant interactions between CRP and other predictors of mortality, indicating that high CRP levels have an additive effect on the mortality risk. These findings show that hemodialysis patients are exposed to both oxidative stress and inflammation.

Acute-Phase Reaction↗
PubMed2001

Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus product in dialysis patients.

Control of serum phosphorus levels is a central goal in the management of patients with chronic renal failure. Inadequate control of serum phosphorus leads to elevated levels of the calcium-phosphorus product. This plays a pivotal role in vascular calcification, cardiovascular disease, calciphylaxis, and death. Elevated phosphorus and elevated levels of the calcium-phosphorus product are both significant predictors of cardiovascular mortality, at phosphorus and calcium-phosphorus product levels that were considered safe until recently. A lowering of levels such that phosphorus is maintained between 2.2 and 5.5 mg/dl, calcium-phosphorus product is below 55 mg(2)/dl(2), and serum calcium is at 9.2-9.6 mg/dl, respectively, might well be the goal of therapeutic management strategies.

Bone and Bones↗
PubMed2001

Pre and interdialytic acid-base balance in hemodialysis patients.

In an observational study, nine hemodialysis patients using 35 mmol/l bicarbonate dialysate were studied over a 44-hour interdialytic interval. Serum bicarbonate was measured at regular intervals at home and the mean time averaged concentration was 27.0+/-1.2 mmol/l. Seven of the nine patients showed a slow linear decline in bicarbonate whilst in two patients levels were unchanged. In 8 of 9 patients the average of the post and predialysis bicarbonate accurately predicted the time-averaged (area under the curve) bicarbonate concentration. In addition, predialysis serum bicarbonate was measured in 46 patients after both a 2 and 3-day interdialytic interval. The serum bicarbonate was significantly lower after the 3-day interdialytic interval (3-day, 22.1+/-0.6 vs 2-day, 23.0+/-0.5 mmol/l, p<0.05). The results from this study emphasize the importance of standardization of bicarbonate measurement in order to avoid spurious acidosis.

Acidosis↗
PubMed2000

Clinical investigation of the role of membrane structure on blood contact and solute transport characteristics of a cellulose membrane.

Regenerated cellulose membranes contain cellulose chains with crystalline and amorphous regions in the direction of extrusion. A study was undertaken to investigate if reduced contact surface arising from alteration of pore size alters biocompatibility (complement activation (C3a and C5a) and neutropenia) and solute transport. The average pore size for the membrane studied (RC HP400A) was 7.23 compared to 2.76 nm for the standard membrane (Cuprophan). C3a levels rose to 6861+/-1595 compared to 2723+/-1228 ng/ml for Cuprophan at 15 min after initial blood contact (P < 0.0001). C5a levels also rose to 30.1+/-11.9 compared to 21.3+/-6.6 ng/ml for Cuprophan (P = 0.18). Both fractions gradually returned to baseline levels thereafter. Circulating white cell count fell rapidly over the same time period to 39+/-17% of the baseline value by 15 min and was similar to Cuprophan (27.5+/-11.2%) (P = 0.25). A small (< 10%) change in platelet numbers was noted for both membranes. Removal of urea (60 Da) was independent of pore size; however, the RC HP400A removed r2 microglobulin (11818 Da). These findings indicate that pore distribution fails to influence material-induced complement activation but influences large solute transport.

Biocompatible Materials↗
PubMed2000

Clinical performance of a new high-flux synthetic membrane.

The clinical performance during first use of a new membrane manufactured from a blend of polyarylethersulfone and polyvinylpyrrolidone (Arylane; Hospal Renal Care, Lyon, France), in which the microstructure of the membrane has been tailored by the manufacturing process and polymer blend, has been compared with Fresenius Polysulfone (Fresenius Medical Care, Bad Homburg, Germany) in a prospective, randomized, crossover study. Small-molecular clearances were similar. A reduction in plasma beta(2)-microglobulin levels was present using both membranes, with a significantly greater removal by Arylane such that the mean postdialysis plasma level difference between the membranes at the end of dialysis was 8. 7 mg/L (95% confidence interval, 3.9 to 13.5; P = 0.004). Recovery of beta(2)-microglobulin from the dialysis fluid was similar: 170 +/- 70 mg for Arylane and 110 +/- 60 mg for Fresenius Polysulfone (P = 0.04). Both membranes were impermeable to albumin but allowed the passage of low-molecular-weight proteins, with 10,046 +/- 3,239 mg for Arylane and 7,285 +/- 2,353 mg for Fresenius Polysulfone recovered from the dialysis fluid (P = 0.07). Neutropenia and platelet adhesion to the membrane were minimal, and time-averaged complement levels during dialysis for C3a and C5b-9 were 207 +/- 92 and 62 +/- 24 ng/mL for Arylane and 223 +/- 68 and 45 +/- 24 ng/mL for Fresenius Polysulfone, respectively, and were membrane independent. This study indicates that the membrane using polyarylethersulfone in conjunction with PVP has complement-activation potential and neutropenia similar to Fresenius Polysulfone but has an enhanced capacity to remove beta(2)-microglobulin. This enhanced removal arises from transmembrane transport augmented by adsorption within the membrane matrix.

Biocompatible Materials↗
PubMed2000

Clinical characterisation of polysulfone LS membrane for renal replacement therapy.

The solute transport characteristics and biocompatibility of a new polysulfone membrane (Polysulfone LS, Fresenius Medical Care, Bad Homburg, Germany) has been established and compared for two different sizes of dialyser (1.3 and 1.8 m2). The in vivo small molecular clearance of the two sizes of dialyser showed an overlap in performance. Neutropenia was slight and independent of the membrane area as were changes in C5adesArg. The membrane induced neutrophil degranulation characterised by the release of elestase alpha1 inhibitor complex with time averaged values over 180 minutes related to membrane area (p=0.010). Heparin activity during dialysis with the membrane was within the therapeutic range necessary for anticoagulation (0.3-1.0 IU/ml), but despite this an increase in thrombin antithrombin 111 levels during treatment was noted. Polysulfone LS extends the range of polysulfone membranes available for clinical use and its performance is such that it may be considered as a membrane for the treatment of patients awaiting a transplant, or in whom use of the high flux therapies may be inappropriate.

Analysis of Variance↗
PubMed1997

Synthetically modified cellulose: an alternative to synthetic membranes for use in haemodialysis?

Renal replacement therapy relies predominantly on the use of cellulose-based membranes. Such membranes have a biocompatibility profile which is inferior to membranes manufactured from synthetic polymers. Synthetically modified cellulose (SMC) is a new, low-flux haemodialysis membrane in which hydroxyl groups have been replaced with benzyl groups. The biocompatibility profile characterized by changes in white cell and platelet counts and the activation of complement components (C3a, C5a and C5b-9) have been studied in vivo and compared with those of cellulose acetate, unmodified cellulose (Cuprophan ) and low-flux polysulphone (Fresenius Polysulfone) in the same group of patients. For SMC, the white cell count at 15 min declined to 65.6% of pretreatment level, compared with 63.8% for the cellulose acetate, 79.6% for low-flux polysulphone and 28.1% for Cuprophan, thereafter returning to pretreatment levels. Both modified cellulose membranes were superior to unmodified cellulose (P = 0.001); the differences between the modified cellulose membranes were not significant statistically. The changes induced by all three cellulose-based membranes exceeded those for low-flux polysulphone (P = 0.001). Associated with the neutropenia was a reduction in platelet count, but this was independent of membrane type. The mean time-averaged concentrations of C3a(des Arg) over 150 min were 1168 ng ml(-1) (SMC), 1030 ng ml(-1) (cellulose acetate), 1297 ng ml(-1) (Cuprophan) and 790 ng ml(-1) (low-flux polysulphone). Equivalent values for C5a(des Arg) were 6.12 (SMC), 2.98 (cellulose acetate), 11.03 (Cuprophan) and 1.33 ng ml(-1) (low-flux polysulphone). C5b-9 values were 385 (SMC), 386 (cellulose acetate), 177 (Cuprophan) and 185 ng ml(-1) (low-flux polysulphone). For each of the complement components the differences between the membranes were significant [P = 0.0009 (C3a(des Arg)), P = 0.0001 (c5a(des Arg) and C5b-9)]. The levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes considered as a single group (Pearson's correlation coefficient = 0.870, P = 0.0001). It is concluded that the modification of the cellobiosic unit is a promising approach to improve the biocompatibility profile of cellulose-based membranes. The two different methods of modification lead to similar improvements in biocompatibility compared with unmodified cellulose, but as yet do not match that of low-flux polysulphone.

Biocompatible Materials↗
PubMed1997

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium.

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium. In this study, the parathyroid response to the correction of acidosis in eight hemodialysis patients was determined by performing dynamic assessment of parathyroid function before and after the correction of acidosis. The parathyroid response to intravenous calcitriol before and after the correction of acidosis was also assessed. After optimal correction of acidosis, there were no significant changes in blood pH, ionized calcium, phosphate, or alkaline phosphatase values, but the level of venous total CO2 increased significantly. Parathyroid hormone/ionized calcium curves were displaced downward after correction of acidosis, but not after the administration of intravenous calcitriol. The correction of metabolic acidosis in hemodialysis patients with secondary hyperparathyroidism can suppress parathyroid hormone secretion by increasing the sensitivity of the parathyroid glands to ionized calcium.

Acidosis↗
PubMed1997

Clinical characterization of Dicea a new cellulose membrane for haemodialysis.

A prospective randomised clinical study comparing the functional performance and biocompatibility of a new cellulose diacetate variant (Dicea) in which the degree of hydroxyl group substitution differs, with cellulose diacetate and low flux polysulfone incorporated into commercially produced hollow fiber hemodialysers with a surface area 1.5-1.6 m2 has been undertaken. All dialysers studied demonstrated clinically acceptable performance in terms of their small molecular removal characteristics, with minor statistical but not clinical differences. Use of both cellulose diacetate membranes but not low flux polysulfone resulted in a reduction in plasma beta(2) microglobulin levels. The membranes were impermeable to albumin, but showed some permeability to low molecular weight proteins. The average protein recovery from the dialysis fluid was 3105 mg for Dicea, 2913 mg for cellulose diacetate and 2842 mg for low flux polysulfone. For Dicea the white cell count by 15 minutes had declined to 68% of pre treatment value, compared with 59% and 86% for cellulose diacetate and low flux polysulfone. The differences between Dicea and cellulose diacetate were not significant, but both cellulose based membranes differed from low flux polysulfone (p = 0.0015). There was a strong evidence of differences between the membranes in respect of C5a and C5b-9 generation (p = 0.0001) but not for C3a (p = 0.16) furthermore the levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes. (Pearson's correlation coefficient = 0.856, p = 0.0001). It is concluded that the two cellulose diacetate membranes are not identical, with the differences observed being a consequence of the degree of acetyl substitution, resulting in alteration of membrane structure and the method of sterilization. The clinical significance of these differences are difficult to characterize but the modification of the cellulose structure appears to be a promising method to improve the biocompatibility of cellulose membranes. The improved biocompatibility offered by this method still falls short of that achieved with low flux synthetic membranes such as Fresenius Polysulfone.

Adult↗
PubMed1996

A comparison of three brands of polysulfone membranes.

A prospective clinical crossover study comparing the functional performance and biocompatibility of three brands of polysulfone membranes (Fresenius Polysultone (Fresenius Ag, Bad Homburg, Germany), Polyphen (Minntech Corp., Minneapolis, MN), and Biosulfane (WR Grace Inc., Danvers, MA)) incorporated in ethylene oxide-sterilized dialyzers of comparable surface area (1.3 to 1.35 m2) was undertaken. The clearance of small molecules by each membrane was comparable. Plasma levels of beta 2 microglobulin fell to 49.9% of pretreatment values by 210 min when using the Fresenius Polysulfone membrane, 60.2% with the Polyphen membrane, and 63.1% with the Biosulfane membrane. The reduction achieved by the Fresenius Polysulfone membrane was superior (P = 0.003). The plasma reductions were associated with the recovery of 195 mg beta 2 microglobulin from the dialysate for the Fresenius Polysulfone membrane and 158 mg for the Polyphen membrane, but no beta 2 microglobulin was recovered from the dialysate with the Biosulfane membrane. The dialysate collected with the Fresenius Polysulfone membrane also contained a mean of 6853 mg of total protein, compared with 5490 mg with the Polyphen membrane and 8422 mg with the Biosulfane (P = 0.04) membrane. The neutropenia was slight and independent of membrane brand, as were the changes in C3a des arg and SC5b-9 complement components. The reduction in platelet counts was higher for the Biosulfane membrane than for the other brands (P = 0.003). This study indicates that whereas the polymer base of the membrane is the same, its production and subsequent handling during dialyzer production induce changes that attain statistical significance, most notably in the way that the membrane removes beta 2 microglobulin and interacts with proteins. The differences observed are a consequence of the different alloying polymers used during manufacture and, consequently, the membranes cannot be considered equivalent.

Adult↗
PubMed1996

Mechanisms and kinetics of the synthesis and release of platelet-activating factor (PAF) by polyacrylonitrile membranes.

Platelet-activating factor is a recognized mediator of anaphylaxis and bioincompatibility. Here, the mechanisms and the kinetics of the production of platelet-activating factor were studied in vivo during high-flux hemodialysis and in vitro in a recirculation model with polyacrylonitrile membranes, the AN-69 and the more recent SPAN, where the Na-metallilsulfonate group is partially substituted with the less polar methacrylate group. In in vivo studies, eleven patients were studied in cross over. Patients were randomly allocated to the AN-69 (5 patients) and to the SPAN membrane (6 patients) for two weeks. Measurements were made in the second week of use. After completion of the second week, the patients were switched to the other membrane for a further two weeks. Samples for leukocyte and platelet counts, PAF in whole blood or bound to platelets, the C3a des Arg and the C5b-C9 membrane attack complex as well as samples for clearances of urea, creatinine and phosphates were taken at different time intervals during treatment. PAF was detected by biological assay after methanol extraction of whole blood or of platelet pellets obtained by sequential centrifugation. C3a des Arg and the C5b-C9 fraction were detected by commercially available immunoassays. Results were analyzed by Minitab statistical package. PAF was detectable only during treatment with AN-69 but not with SPAN 1 min after start of the extracorporeal circulation in both whole blood (4.5 +/- 2.7 ng/ml) and on platelet surface (4.1 +/- 1.2 ng/ml). No statistical significant differences were observed between AN-69 and SPAN with regard to leukocyte and platelet counts, plasma C3a des Arg and C5b-C9 levels. The structure modification did not alter functional performances as indicated by the lack of statistically significant differences in clearance values between the two membranes. In in vitro experiments performed with normal washed and whole blood recirculated in a closed circuit demonstrated the presence of a plasma-dependent, complement-independent mechanisms responsible for the triggering of PAF synthesis and release with AN-69 but not SPAN membrane. PAF was extractable from the inner and outer side of both polyacrylonitrile membranes (AN-69: inner, 4.9 +/- 0.5 ng/ml; outer, 0.1 +/- 0.05 ng/ml; SPAN: inner, 5.5 +/- 0.6 ng/ml, outer: 3.3 +/- 0.7 ng/ml, SPAN vs. p < 0.001), suggesting that absorption may be relevant with both membranes.

Acrylic Resins↗