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R Deppisch

Publications and source records attributed to R Deppisch.

At least 19 recordsLinked to original sources
PubMed2001

Uremic toxicity: present state of the art.

The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal condition are excreted by the healthy kidneys (uremic toxins). In the area of identification and characterization of uremic toxins and in the knowledge of their pathophysiologic importance, major steps forward have been made during recent years. The present article is a review of several of these steps, especially in the area of information about the compounds that could play a role in the development of cardiovascular complications. It is written by those members of the Uremic Toxins Group, which has been created by the European Society for Artificial Organs (ESAO). Each of the 16 authors has written a state of the art in his/her major area of interest.

Cardiovascular Diseases↗
PubMed2000

One-year immunological evaluation of chronic hemodialysis in end-stage renal disease patients.

BACKGROUND: Much research has been devoted to the determination of acute leukocyte activation as well as acute cytokines production during and after blood hemodialysis membrane interaction. In contrast, few studies deal with chronic immunological evaluation of T-cell activation markers in hemodialysis. METHODS: We evaluated different immune parameters using a modified cellulose low-flux hemophan vs. synthetic high-flux polyamide membrane during 1 year in 35 stable chronic hemodialysis patients. Leukocyte counts, lymphocyte subpopulations, T-cell activation markers (CD69, CD25, HLA-DR, CD54, CD62L, CD45RO, CD11a, CD28), complement-activation products (C3a) and serum elastase were measured at 0, 3, 6 and 12 months in the two patient groups and compared to 13 healthy control subjects. RESULTS: Over dialysis time, all patients showed a significant level elevation of CD69/CD3 (p < 0.005) and CD25/ CD3 (p < 0.005) phenotypes. In contrast, HLA-DR and CD45RO remained unchanged suggesting a truncated pattern of activation. T lymphocyte subset analysis showed in both hemodialyzed groups a significant decrease in the expression of CD54 (ICAM-1) when compared to controls (p < 0.005). C3a and elastase measurements showed a significant upward trend with dialysis time in both hemodialyzed groups. CONCLUSION: Although the immunological changes seen in chronic hemodialyzed patients must be interpreted in conjunction with their basal uremic states and the membrane permeability properties, our study suggests that 1-year immunological evaluation of hemodialysis membranes biocompatibility is associated with changes in the pattern of chronic T-cell activation, which is in part related to the use of a particular membrane type. Moreover, some key molecules (CD54) are affected in patients with end-stage renal disease undergoing hemodialysis.

Aged↗
PubMed2000

Biological significance of reducing glucose degradation products in peritoneal dialysis fluids.

UNLABELLED: Carbohydrates are not stable when exposed to energy; they degrade into new molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs during the heat sterilization procedure. The biological consequences of this degradation are side effects such as impaired proliferation and impaired host defense mechanisms, demonstrated in vitro for a great variety of cells. Several highly toxic compounds--such as formaldehyde and 3-deoxyglucosone--have been identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also well-known promoters of irreversible advanced glycation end-products (AGEs), which might participate in the long-term remodeling of the peritoneal membrane. Various approaches can be used to reduce the formation of glucose degradation products (GDPs) during heat sterilization. Some examples are shortening the sterilization time, lowering the pH, removing catalyzing substances, and increasing glucose concentration. The latter three factors are employed in the multi-compartment bag with a separate chamber containing pure glucose at high concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows reduced cytotoxicity, normalized host defense reactions, less AGE formation, and reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the clinical situation, the fluid turns out to be more biocompatible for the patient, causing less mesothelial cell damage, which in the long term could lead to a more intact peritoneal membrane. CONCLUSION: Glucose degradation products in heat-sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation, and cause negative side effects for the patient. Using improved and well-controlled manufacturing processes, it is possible to produce sterile PD fluids with glucose as the osmotic agent but without the negative side effects related to GDPs.

Cells, Cultured↗
PubMed1999

Advanced glycated end-products (AGE) during haemodialysis treatment: discrepant results with different methodologies reflecting the heterogeneity of AGE compounds.

BACKGROUND: There has been much recent interest in accumulation of advanced glycation end-products (AGE) in uraemic patients. Analysis of AGE has been difficult, because commonly used methodologies, i.e. immunodetection assays or fluorescence measurements, reflect group reactivity and are not specific for chemically defined substances. Some investigators measured individual AGE compounds, e.g. pentosidine, carboxymethyllysine, pyrraline or imidazolone, but a systematic assessment of known compounds using specific HPLC methods in diabetic and non-diabetic end-stage renal disease (ESRD) patients during treatment has not been performed. METHODS: For the present study, the concentrations of early and late products of the Maillard reaction in plasma and ultrafiltrate were monitored during high-flux dialysis sessions in diabetic and non-diabetic patients. AGE were analysed by fluorescence spectroscopy and size exclusion chromatography with fluorescence detection. Specific HPLC methods were used to quantify the Amadori product fructoselysine and the AGE compounds pentosidine and pyrraline in acid or enzymatic hydrolysates. RESULTS: Using size exclusion chromatography, we confirmed a similar fluorescent peak distribution for diabetic and non-diabetic ESRD patients. Main fractions were found at approximately 70, approximately 14 and <2 kDa, confirming results obtained by other authors. In diabetic patients, the fluorescence intensity of the low molecular weight fraction was higher. Uraemic patients differed from controls mainly by the fluorescence of the low molecular weight fraction. The peak spectrum in ultrafiltrates was similar to that in plasma regarding low molecular weight fractions and the 14 kDa peak, but no protein-bound fluorescence was found at 70 kDa. HPLC analysis revealed a significant reduction of plasma pentosidine during high-flux dialysis in non-diabetic (from 9.1+/-5.1 to 8.5+/-4.7 pmol/mg protein; P<0.05) and diabetic patients (from 10.0+/-9.1 to 6.8+/-4.0 pmol/mg protein; P<0.05). In contrast, plasma fructoselysine showed only a non-significant trend to decrease in diabetic (from 3.24+/-0.88 to 3.05+/-0.77 nmol/mg protein) and non-diabetic patients (from 2.69+/-0.52 to 2.56+/-0.50 nmol/mg protein). Pyrraline, a nonfluorescent late AGE product derived from reaction of 3-deoxyglucosone with lysine, could not be detected (detection limit approximately 40 pmol/mg protein). Comparing HPLC and size exclusion analysis, it was found that pentosidine accumulated in the range of low molecular weight substances and was removed by high-flux dialysis. CONCLUSIONS: High-flux dialysis reduces the plasma concentration of fluorescent AGE compounds, i.e. pentosidine, but the Amadori product fructoselysine is not removed, indicating that this compound is protein associated.

Adult↗
PubMed1997

Impact of membrane choice and blood flow pattern on coagulation and heparin requirement--potential consequences on lipid concentrations.

BACKGROUND: We reasoned that procoagulant activity, and by implication heparin requirement, during haemodialysis are influenced, amongst other factors, by the type of membranes and the geometry of the blood line system. In addition, there are indications that heparin has dose-dependent effects on the lipid status of chronic haemodialysis patients. METHODS: In a parallel group design we compared patients treated with cuprophane (CU) and polycarbonate-polyether (PC-PE) plate dialysers. In both groups, blood line geometry was varied by including in a first phase and omitting in a second phase drip chambers in the arterial blood line. End-points were changes in coagulation parameters, i.e. thrombin-antithrombin III complex (TAT), plasmin-anti-plasmin complex (PAP), and prothrombin fragment (F1 + 2) concentrations measured by sandwich ELISA. Subsequently all patients were switched to PC-PE dialysers for 6 months and the heparin dose was reduced in a stepwise fashion. Lipid levels and coagulation parameters were monitored. Finally, in an ancillary study, the correlation between heparin dose and LDL/HDL ratio was assessed in patients chronically exposed to PC-PE membranes and low doses of heparin. RESULTS: Post-dialytic concentrations of coagulation and fibrinolysis parameters were significantly lower in the PC-PE group (TAT 31.0 +/- 4.4 micrograms/l; PAP 1180 +/- 148 micrograms/l; F1 + 2 4.2 +/- 0.4 nmol/l) compared to the CU group (TAT 57.3 +/- 10.8 micrograms/l; PAP 1789 +/- 185 micrograms/l; F1 + 2 8.8 +/- 1.0 nmol/l), independently of the use of an arterial drip chamber. Omission of the arterial drip chamber led to lower TAT in the CU group (42.2 +/- 5.8 micrograms/l, P < 0.05), but not in the PC-PE group. In contrast, PAP and F1 + 2 concentrations did not change significantly in either group. Down-titration of heparin dose (from 20.4 +/- 1.1 to 9.4 +/- 0.9 IU/kg/h) was associated with a significant decrease in serum triglycerides (from 2.9 +/- 0.9 to 2.0 +/- 0.6 mmol/l, P < 0.05), LDL-cholesterol (from 3.4 +/- 0.2 to 2.7 +/- 0.4 mmol/l, P < 0.05) and LDL/HDL-ratio (from 3.2 +/- 0.3 to 2.0 +/- 0.3, P < 0.05) with no significant change of total or HDL-cholesterol after 6 months. In an ancilliary analysis, a correlation between lipid parameters (LDL/HDL ratio) and heparin dose was confirmed in 24 patients chronically exposed to PC-PE membranes (r = 0.473, P < 0.05). CONCLUSIONS: In a prospective exploratory study (i) heparin requirement is lower with the use of a polycarbonate-polyether membrane compared to a cuprophane membrane, (ii) heparin requirement is influenced by blood line geometry (decreased with omission of an arterial drip chamber), and (iii) in patients on polycarbonate-polyether membranes down-titration of heparin is associated with a reduction of serum triglycerides, LDL cholesterol, and LDL/HDL ratio. Our data suggest that reduction of heparin dose improves lipid profile. These preliminary observations require confirmation by parallel group controlled studies with controlled dietary intake.

Aged↗
PubMed1996

Effect of hemofiltration on hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis.

OBJECTIVE: To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. DESIGN: Prospective observation study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 16 patients with severe sepsis. INTERVENTIONS: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2 l/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0 = 676.9 +/- 99.7 ng/ml vs t12 = 467.8 +/- 71, p < 0.01; C5adesArg: 26.6 +/- 4.7 ng/ml vs 17.6 +/- 6.2, p < 0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669 +/- 85 dyne.s/cm5 vs SVR at t12: 864 +/- 75, p < 0.01; MAP at t0: 69.9 +/- 3.5 mmHg vs MAP at t12: 82.2 +/- 3.7, p < 0.01). CONCLUSIONS: HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.

Adult↗
PubMed1996

Activation of human neutrophils after contact with cellulose-based haemodialysis membranes: intracellular calcium signalling in single cells.

PURPOSE OF STUDY: In vitro contact of human leukocytes with cellulose-based dialysis membranes under complement-independent conditions results in activation of various leukocyte functions. To analyse signals involved in the mechanism of cell activation, we measured changes in cytosolic free calcium ([Ca2+]i) in individual human blood neutrophils (PMN) upon contact with flat sheet haemodialysis membranes. RESULTS: By confocal laser-scanning microscopy (CLSM), changes in [Ca2+]i were monitored in Fluo-3-labelled cells up to 10 min after contact with a regenerated cellulose (RC) membrane. Multiple [Ca2+]i transients were observed for cells in contact with RC; biostochastic analysis showed that up to 67% of the PMN responded with a high increase in [Ca2+]i, the rest were low- or non-responding cells. After contact with the new synthetic polycarbonate-polyether (PC-PE) membrane only non-responding cells were seen, indicating reduced cellular contact activation. The increase in [Ca2+]i of cells on RC could be inhibited by 5mM L-fucose. This monosaccharide was recently found to be present in cellulose-based polymers in picomolar concentrations. CONCLUSIONS: The data supports the hypothesis that dialysis-membrane-associated L-fucose residues participate in complement-independent leukocyte activation during haemodialysis therapy.

Biocompatible Materials↗
PubMed1995

L-fucose residues on cellulose-based dialysis membranes: quantification of membrane-associated L-fucose and analysis of specific lectin binding.

Contact of mononuclear human leukocytes with cellulose dialysis membranes may result in complement-independent cell activation, i.e. enhanced synthesis of cytokines, prostaglandins and an increase in beta 2-micro-globulin synthesis. Cellular contact activation is specifically inhibited by the monosaccharide L-fucose suggesting that dialysis membrane associated L-fucose residues are involved in leukocyte activation. In this study we have detected and quantitated L-fucose on commercially-available cellulose dialysis membranes using two approaches. A sensitive enzymatic fluorescence assay detected L-fucose after acid hydrolysis of flat sheet membranes. Values ranged from 79.3 +/- 3.6 to 90.2 +/- 5.0 pmol cm-2 for Hemophan or Cuprophan respectively. Enzymatic cleavage of terminal alpha-L-fucopyranoses with alpha-L-fucosidase yielded 7.7 +/- 3.3 pmol L-fucose per cm2 for Cuprophan. Enzymatic hydrolysis of the synthetic polymer membranes AN-69 and PC-PE did not yield detectable amounts of L-fucose. In a second approach, binding of the fucose specific lectins of Lotus tetragonolobus and Ulex europaeus (UEAI) demonstrated the presence of biologically accessible L-fucose on the surface of cellulose membranes. Specific binding was observed with Cuprophan, and up to 2.6 +/- 0.3 pmol L-fucose per cm2 was calculated to be present from Langmuir-type adsorption isotherms. The data presented are in line with the hypothesis that surface-associated L-fucose residues on cellulose dialysis membranes participate in leukocyte contact activation.

Acrylic Resins↗
PubMed1995

Hemofiltration in human sepsis: evidence for elimination of immunomodulatory substances.

Continuous hemofiltration is widely used for renal replacement therapy in patients with acute renal failure. It has been suggested that hemofiltration may also eliminate toxic mediators thought to be important in the pathophysiology of sepsis. The present study examined whether hemofiltration can activate or eliminate inflammatory mediators in patients with sepsis, and whether ultrafiltrate can alter specific functions of peripheral blood mononuclear leukocytes (PBMC) in vitro. Veno-venous hemofiltration was performed in 16 patients and in 5 healthy volunteers. Pre-filter (afferent), post-filter (efferent) and ultrafiltrate concentrations of cytokines (IL-1 beta, IL-6, IL-8, TNF alpha) and of complement components (C3, C3adesArg, C5adesArg, terminal complement complex) were measured after the beginning of hemofiltration (t0), and 60 minutes later (t60). PBMC, and monocyte and lymphocyte subfractions were incubated with ultrafiltrate, and cytokines were determined in the supernatants. Hemofiltration did not induce significant mediator activation. There was no evidence for significant cytokine elimination. However, pre-filter C3adesArg concentration showed a significant decline during hemofiltration (patients: t0 = 676.9 +/- 99.7 ng/ml, t60 = 545.4 +/- 83.2, P < 0.001; volunteers: t0 = 54.8 +/- 13.3 ng/ml, t60 = 33.9 +/- 10.7, P < 0.001). Ultrafiltrate from septic patients significantly stimulated PBMC and monocyte TNF alpha release, but suppressed lymphocyte IL-2 and IL-6 production. Ultrafiltrate from volunteers was without effect. Hemofiltration effectively eliminates certain mediators such as C3adesArg. Ultrafiltrate contains compounds with significant immunomodulatory qualities. Therefore, hemofiltration may represent a new modality for removal of immunomodulatory mediators.

Adjuvants, Immunologic↗
PubMed1995

Immunological determination of advanced glycosylation end-products in human blood and urine.

Advanced glycosylation end-products (AGE) in human blood and urine were investigated with the aid of an AGE-specific enzyme-linked immunosorbent assay. Evidence is presented that AGE are natural constituents of human serum and urine. In diabetics with normal renal function only a small increase in serum AGE levels was found as compared to normal controls, while no difference in urinary excretion rate was discernible. Urinary excretion rate of AGE from diabetic and non-diabetic patients with end-stage renal disease was reduced, while high serum AGE levels were observed. AGE in serum occur in a low-molecular-weight fraction and in a possibly protein-bound high-molecular-weight fraction. In urine from normal controls three immunologically reactive fractions were detected whose apparent molecular mass ranged from 100 to 1000 Daltons, while in urine from patients with end-stage renal failure additional high-molecular-weight fractions appeared.

Adolescent↗
PubMed1995

In vitro biocompatibility of a heat-sterilized, low-toxic, and less acidic fluid for peritoneal dialysis.

OBJECTIVE: The aim of this study was to investigate a peritoneal dialysis (PD) fluid (PD-Bio), produced with the intention of reducing the amount of glucose degradation products and to increase the final pH. The heat sterilization of the fluid was performed with the glucose separated from the electrolytes. After sterilization the two solutions were combined. METHODS: The in vitro biocompatibility of PD-Bio was measured as the inhibition of cell growth of a cultured fibroblast cell line and as the stimulated release of interleukin-1 beta from cultured human mononuclear cells. The glucose degradation products were measured as UV absorbance at 228 nm or 284 nm and the concentration of aldehydes was estimated with high-performance liquid chromatography and gas chromatography. RESULTS: Our results demonstrate that in comparison to conventional PD fluids the pH of PD-Bio was increased, to about 6.5. Due to less contaminating glucose degradation products in PD-Bio, basal cytotoxicity was significantly decreased for both 1.5% and 4% glucose-containing fluids, and the stimulated release of interleukin-1 beta was normalized compared to sterile filtered controls with the same pH. UV absorbance measured at 228 nm was decreased, whereas the absorbance at 284 nm was equal to that of a conventional fluid. In PD-Bio the concentrations of formaldehyde, acetaldehyde, methylglyoxal, and 2-furaldehyde were found to be below the detection limit, whereas glyoxal was present in the same and 5-hydroxymethylfurfural (5-HMF) in higher concentrations than in conventionally produced PD fluid. CONCLUSIONS: The results demonstrate that it is possible to improve biocompatibility of PD fluids by simply changing the way the fluid is produced.

Acetaldehyde↗