Plasma levels of granulocyte elastase during hemodialysis: Effects of different dialyzer membranes

Plasma levels of granulocyte elastase during hemodialysis: Effects of different dialyzer membranes. Plasma levels of granulocyte elastase in complex with α1-proteinase inhibitor during hemodialysis were investigated in 15 patients (37.4 ± 3.2 years) undergoing maintenance hemodialysis (47.0 ± 12.9 months) with dialyzers made from cellulose hydrate, cuprophan, polymethylmethacrylate, ethylene-vinyl alcohol copolymer, and polyacrylonitrile. Cellulose hydrate membrane caused a maximal increase of the plasma levels of granulocyte elastase in complex with α1-proteinase inhibitor (E-α1PI: 1,659.0 ± 256.8 ng/ml). Patients dialyzed with polyacrylonitrile dialyzers failed to exhibit comparable plasma levels of granulocyte elastase (E-α1 237.8 ± 22.9 ng/ml). During hemodialysis plasma E-α1PI values rose to a peak 643.0 ± 174.7 ng/ml in patients on polymethylmethacrylate dialyzers, to 557.5 ± 120.0 ng/ml on cuprophan dialyzers, but to only 381.9 ± 54.0 ng/ml on ethylene-vinyl alcohol copolymer dialyzers. Plasma lysozyme levels decreased significantly in the presence of polyacrylonitrile and polymethylmethacrylate membranes. We conclude that the degree of PMNs stimulation depends on the nature of the dialyzer membrane material. The following membranes induce a reaction of increasing intensity: polyacrylonitrile, ethylene-vinyl alcohol copolymer, cuprophan, polymethylmethacrylate, and cellulose hydrate

Mortality in renal transplant recipients given erythropoietins to increase haemoglobin concentration: cohort study

Objective To determine the optimal range of increase in haemoglobin concentration with treatment with erythropoietins that is safe and is not associated with mortality

Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils

Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils. Clearance of neutrophils via apoptosis from the site of infection is crucial for the coordinated resolution of inflammation. The balance between stimulating and attenuating as well as between pro-and anti-apoptotic factors in necessary for maintenance of an effective immune response without the harmful side effects of neutrophil action. This article describes the effect of glucose-modified serum proteins and of free immunoglobulin light chains (IgLCs) on neutrophil functions and apoptosis. Both groups of proteins are found a elevated levels in sera of uremic patients. Glucose-modified proteins increase both the chemotactic movement of neutrophils and the activation of glucose uptake. Spontaneous neutrophil apoptosis in increased in the presence of these modified serum proteins. On the other hand, the presence of free IgLCs, previously shown to diminish neeutrophil chemotaxis and the activation of glucose uptake, increase the percentage of viable neutrophils by inhibiting spontaneous apoptotic cell death. We conclude that both glucose-modified proteins and free IgLCs can be considered to be uremic toxins and both contribute to the disturbed immune function in uremic patients. Their concentrations as well as the microenvironment in which they are acting seem to be important for their actual effects

PRE‐dialysis survey on anaemia management

Background. The PRE‐dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre‐dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. Methods. For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. Results. A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration ≤11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r=0.43, P<0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration ≤11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. Conclusions. Few pre‐dialysis patients met the EBPG target for Hb concentration, despite regular nephrology car

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients.BackgroundCurrently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B12, folate, or total homocysteine (tHcy).MethodsIn a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B12, folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.ResultsThe allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N = 72) or homozygosity (N = 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B12 (P = 0.33) or tHcy (P = 0.70), but a borderline association with higher folate concentrations was detected (Δfolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P = 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B12 concentrations.ConclusionHigher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B12 in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients.BackgroundIron deficiency and anemia are commonly encountered in patients with autoimmune diseases undergoing immune apheresis. This makes erythropoietin and iron substitution necessary in most patients. However, intravenous iron therapy may result in an increase of potentially toxic nontransferrin-bound iron.MethodsWe examined the effect of 50 mg or 100 mg of iron (III) sucrose on bleomycin-detectable iron (BDI) in immune apheresis patients. Six patients with autoimmune disorders and normal kidney function were enrolled. Before and after the injection of 50 mg or 100 mg of iron (III) sucrose, BDI was measured in serum samples at five different time points.ResultsThere was no BDI traceable before injection of iron (III) sucrose. BDI was present in serum of all patients after the administration of 100 mg of iron (III) sucrose in concentrations up to 0.49 μmol/L. In contrast, only one patient showed BDI at a concentration of 0.16 μmol/L after the administration of 50 mg of iron (III) sucrose.ConclusionWe conclude that if parenteral iron is administered after apheresis treatment, despite the equal tolerability, use of 50 mg of iron (III) sucrose is superior to 100 mg of iron (III) sucrose in avoiding the formation of potentially toxic nontransferrin-bound iron

Mutation (677C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients

Mutation 677C to T in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients. Hyperhomocysteinemia is frequent in hemodialysis patients and represents an independent risk factor for vascular disease in these patients. Elevated total homocysteine (tHcy) plasma levels can result from defective remethyla-tion of Hcy to methionine due to decreased activity of the enzyme methylenetetrahydrofolate reductase (MTHFR). A genetic aberration in the MTHFR gene (677C to T substitution) has been shown to result in reduced MTHFR activity. We tested the hypothesis that elevation of tHcy plasma levels in hemodialysis patients is influenced by the 677C to T mutation of the MTHFR gene and examined the relation of the genotype with tHcy, folate and vitamin B12 plasma levels in these patients. The allelic frequency of the MTHFR mutation was evaluated in 203 patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in 69 age- and sex-matched healthy control subjects. The allelic frequency of the 677C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus 35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/−) genotype was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level in hemodialysis patients was 28.7 ± 11.0 µuunol/liter versus 10.0 ± 3.0 µmol/liter in control subjects. The mean tHcy levels were 36.4 ± 13.4 µmol/liter in (+/+) patients and 12.2 ± 4.5 /mol/liter in (+/+) controls, 28.7 ± 10.8 µmol/liter in (+/−) patients and 9.9 ± 2.7 µmol/liter in (+/−) controls and 25.4 ± 8.5 µmol/liter in (−/−) hemodialysis patients versus 9.7 ± 2.8 µmol/liter in (−/−) controls. There was no significant difference of folate and vitamin B12 concentrations in patients and controls with different MTHFR genotypes. Analysis of covariance including age, gender, folate concentrations, vitamin B12 levels, albumin and creatinine as covariables revealed a significant influence of the (+/+) genotype, albumin and folate status on tHcy levels in hemodialysis patients. Together, our data demonstrate that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of uremia or folate status, but is also genetically determined by the (+/+) MTHFR genotype. The presence of the 677C to T mutation in the MTHFR gene does not appear to represent a risk factor for development of end-stage renal disease

Effect ofMTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients

Effect ofMTHFRgenotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients.BackgroundThe total homocysteine (tHcy) plasma level, which is partly determined by theMTHFR 677C→T genotype, may be associated with vascular disease. We prospectively examined the influence ofMTHFR genotypes (677C→T, 1298A→C) and tHcy plasma concentration on all cause mortality and graft outcomes of renal transplant recipients.MethodsBaseline tHcy plasma levels of 189 patients (three groups with either theMTHFR 677CC, CT or TT genotype, including 63 patients in each group, were matched for age, gender, body mass index and creatinine clearance at baseline), were obtained between September 1996 and May 1997. Follow-up data (time until return to dialysis therapy, time and cause of death) were collected from April to June 1999. Kaplan-Meier survival estimations were calculated and plotted, the groups (threeMTHFR 677C→T genotype groups, or threeMTHFR 1298A→C genotype groups, or two groups with tHcy plasma levels above/below 15 μmol/L) were compared by log-rank test. Age, gender, body mass index (BMI), time since transplantation, serum creatinine, creatinine clearance, combinedMTHFR 677C→T/1298A→C genotypes, tHcy, folate and vitamin B12 plasma levels were evaluated with regard to graft and patient survival in a multivariate Cox-proportional hazard regression model.ResultsDuring the follow-up period of 2.26 ± 0.66 years, 9 patients died (5 in the TT, 2 in the CT and 2 in the CC genotype group;P = 0.34) and 22 returned to dialysis treatment (7 in the TT, 9 in the CT and 6 in the CC genotype group;P = 0.65). There was also no influnce ofMTHFR 1298A→C genotypes (AA genotype, 114 patients; AC genotype, 64 patients; CC genotype, 11 patients) on patient or graft survival (P = 0.7087 andP = 0.1633, respectively). Two of 93 patients with a tHcy plasma level ≤15 μmol/L died, in contrast to 7 of 96 patients in the low tHcy > 15 μmol/L group,P = 0.0778. Two patients in the low tHcy group had to return to dialysis, in contrast to 20 patients in the high tHcy group (P = 0.0001). In the multivariate model there was no significant predictor of patient survival, and the serum creatinine was the only predictor of graft survival (P < 0.0001).ConclusionsIn summary, our study shows that neitherMTHFR 677C→T/1298A→C genotypes nor hyperhomocysteinemia are independently associated with patient or graft survival following kidney transplantation