Ultrafiltrable aluminium after very low doses of desferrioxamine

Background: The recommended dose of desferrioxamine for the treatment of aluminium intoxication is 5 mg/kg/week. However there are no data about the efficiency of lower doses. The objective of this study was to investigate the capacity of very low doses of desferrioxamine in the generation of ultrafiltrable aluminium. Methods: Five patients undergoing haemodialysis with a similar biochemical profile and serum aluminium levels >40 &mgr;g/l were studied. The three different doses of desferrioxamine used (0.5, 2.5 and 5.0 mg/kg) were admonished randomly to each patient at 1 week intervals. Total and ultrafiltrable serum aluminium was measured before and 44 h after the administration of desferrioxamine. Results: All doses of desferrioxamine significantly increased the total serum aluminium; no differences were found between 2.5 and 5.0 mg/kg. The total serum aluminium levels doubled with the 2.5 and 3.0 mg/kg doses, while the increase with 0.5 mg/kg was lower 32.6%, P<0.05). Ultrafiltrable aluminium increased with the three doses; from 7.1±2.8, 3.9±0.6 and 7.5±4.1 to 25.7±7.3, 44.3±10.1 and 59.1±19.9 &mgr;g/l, respectively (P<0.05). The efficiency of each dose was calculated using the ratio between the increase in ultrafiltrable aluminium and the dose of desferrioxamine administered. The efficiency ranged from 10.3±3.9 for the higher dose (5 mg/kg) to 27.2±10.3 for the lower dose (0.5 mg/kg). Conclusions: Our results suggest that very low-dose desferrioxamine (>5 mg/kg) increases the ultrafiltrable (potentially dialysable) aluminium.     

Relative roles of intestinal absorption and dialysis-fluid-related exposure in the accumulation of aluminium in haemodialysis patients

Background: A recent retrospective study has clearly demonstrated a reduction of cases with positive bone aluminium (A1) staining in the Italian dialysis population, which in general has had a low prevalence of bone A1 toxicity. In the present study we tried to better address the relative role played, in our study population, by enteral and parenteral exposure to A1 in reducing bone accumulation. Methods: We retrospectively examined the data of 105 DFO tests and bone A1 determinations performed in dialysis patients from 1984 to 1995. Enteral exposure was analysed by accurate anamnestic records, while parenteral exposure was evaluated by the determination of A1 content in dialysis fluids. Bone A1 content was assayed chemically and histochemically, while serum A1 was assayed spectrophotometrically. Data pertinent to the patients were allotted into three period groups: 1984-1987; 1988-1991; 1992-1995. As for A1 concentrations in dialysis fluids, the interval 1980-1983 (immediately before the start of our study), which could clearly have influenced bone A1 content, was also considered. Results: Basal serum A1 showed some fluctuations (42.7±34.1; 24.8±21.9 and 38.9±224.9 &mgr;g/l respectively in the three groups, ANOVA P <0.01) but only values of the period 1988-1991 were significantly lower than those of the period 1984-1987 (P <0.05). Increments after the DFO did not differ in the three periods (136.5±105.7; vs 98.7±91.7 and 106.1±96.2 &mgr;g/l respectively, P=n.s). Enteral exposure to drugs containing A1 was comparable (4.1±2.9 vs 4.0±4.6 and 5.8±7.9 total kg ingested respectively; P=n.s.), but bone A1 was dramatically reduced (from 60.7±43.0 to 29.0±24.4 and 31.9±29.9 mg/dg/dw respectively; P <0.0001), along with the definite disappearance of Aluminon-positive cases and A1-related bone disease (ARBD) after 1991. Parenteral exposure through the dialysate dropped from a mean 26±14 &mgr;g/l in the 4-year period prior the start of the study (1980-1983) to 9±6 &mgr;g/l in the period 1984-1987 and to 4.9±2.1 &mgr;g/l and 5.0±2.0 &mgr;g/l respectively thereafter (P <0.0001). Conclusions: Despite the persistence of oral exposure to A1, responsible for the observed stability of serum A1 levels, a definite reduction of bone A1 content has been recorded in our dialysis population, and ARBD has disappeared. This result has to be referred essentially to the optimal control of A1 content in dialysis fluids, which is confirmed as a major factor for A1 intoxication. Key words: aluminium hydroxide; aluminium toxicity; bone aluminium; desferrioxamine test; dialysate aluminium; dialysis fluids; haemodialysis      

Silicon and aluminium interactions in haemodialysis patients

Background: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. Methods: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. Results: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) &mgr;mol/l when serum silicon was less than 150 &mgr;mol/l, and lower, 1.1 (0.2-2.8) &mgr;mol/l when serum silicon levels were greater than 150 &mgr;mol/l (P=0.03). Conclusions: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.     

Iron absorption in erythropoietin-treated haemodialysis patients; effects of iron availability, inflammation and aluminium

Background: The response to recombinant human erythropoietin (rHuEpo) is determined primarily by the availability of iron. In contrast to i.v. iron, oral iron supplementation is often insufficient for an optimal response. Method: We studied iron absorption and the effects of iron status, aluminium status and inflammation in 19 chronic haemodialysis patients on maintenance rHuEpo therapy. Iron mucosal uptake after 24 h, iron retention after 2 weeks and mucosal transfer of iron were determined with a whole-body counter using an oral dose ⁵⁹Fe. Iron absorption was measured once without, and once after the ingestion of 2 g aluminium hydroxide. Results: On the basis of transferring saturation, two groups of dialysis patients were distinguished: a group with a functional iron deficiency (n=9), and an iron-deficient dialysis patients group, mucosal uptake, mucosal transfer, and iron retention were 49.9%±29.4, 0.73±0.29, and 41.6%±32.2, being significantly lower than in a non-uraemic iron deficient population (P <0.01, P <0.05, P <0.01 respectively). In the iron-replete dialysis patients group, mucosal uptake, mucosal transfer, and iron retention were 20.0±12.3, 0.59±0.18, and 11.1±6.7, mucosal uptake and iron retention being lower than in a normal iron-replete population (P <0.0005 and P <0.003 respectively). Dialysis patients with high C-reactive protein (CRP) values showed lower iron absorption. Iron absorption data correlated significantly with transferrin saturation and CRP in the iron-deficient group, and with serum ferritin in the iron-replete group. Iron absorption decreased after an aluminium hydroxide challenge in the iron-deficient patients to the lower levels of the iron-replete subjects. Body aluminium stores, estimated by the desferrioxamine test, did not correlate with parameters of iron absorption. Conclusion: The absorption of iron in dialysis patients is decreased in haemodialysis patients, which may, at least in part, be due to inflammation. Aluminium ingestion further reduces absorption in functional iron-deficient patients. Key words: anaemia; erythropoietin; iron absorption; haemodialysis      

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial

Background: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. Methods: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 &mgr;g twice a week, n=10) or daily (0.75 &mgr;g a day, n=8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. Results: Pharmacokinetic analysis after a single dose of 3.0 &mgr;g (pulse) vs 0.75 &mgr;g (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse=562±291 vs daily=454±113 pg/ml), calcium (pulse=2.32±0.20 vs daily=2.32±0.12 mmol/l) and phosphorus (pulse=1.32±0.52 vs daily=1.35±0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and rate of decline in PTH were similar (time: pulse=14.2±6.8 weeks, daily=12.2±7 weeks; rate: pulse=7.4±4.2 vs daily=8.4±4.2% PTH/week; P=NS). The serum calcium increased similarly in both groups. Hypercalcaemia (>2.9 mmol/l) was rare (pulse=3, daily=2 episodes). Conclusions: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy. Key words: calcitriol; calcium balance; CAPD; dialysis; hyperparathyroidism; renal osteodystrophy      

Evidence for disturbed S-adenosylmethionine: S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions?

Background: Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. Methods: In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. Results: Folic acid and vitamin B12 in plasma were similar in patients (mean±SEM 25±2 nmol/l and 400±41 pmol/l respectively) and controls (24±3 and 324±23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6±3.6 &mgr;mol/l, 381±32 nmol/l and 1074±55 nmol/l respectively) compared to the control values (6.8±0.4 &mgr;mol/l, 60±3 nmol/l and 24.4±1.2 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36±0.02 and 2.7±0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. Conclusion: Since the ratio of S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients. Key words: S-adenosylhomocysteine; S-adenosylmethionine; cardiovascular disease; end-stage renal disease; homocysteine; methylation      

Deferoxamine and aluminum clearance in pediatric hemodialysis patients

Mobilization of aluminum by deferoxamine and the subsequent clearance from plasma by hemodialysis with or without charcoal hemofiltration was studied in four pediatric patients. Deferoxamine, 10–20 mg/kg, followed by dialysis with a Travenol CA50 dialyzer produced reductions in mean plasma aluminum levels from 2433±729 nmol/l (65.5±19.6 g/l) to 1727±554 nmol/l (46.5±14.9 g/l) during dialysis. The use of a charcoal cartridge in the circuit resulted in a reduction in mean plasma aluminum levels 2459±591 nmol/l (66.2±15.9 g/ml) to 1380±106 nmol/l (35.8±2.9 g/l). In one patient, high-flux dialysis produced a reduction from 2140 nmol/l (55.6 g/l) to 1134 nmol/l (29.4 g/l). No patients suffered direct adverse reactions to low-dose deferoxamine, although two patients had previously exhibited potential aluminum neurotoxicity after rapid increases in plasma aluminum levels with deferoxamine in higher doses. Aluminum levels must be monitored closely during deferoxamine therapy in uremic children to minimize the risk of exacerbating aluminum neurotoxicity.     

Atrial natriuretic peptide and cyclic 3′5′-guanosine monophosphate as indicators of fluid volume overload in children with chronic renal failure

Plasma atrial natriuretic peptide (ANP) and cyclic 35-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n=17, mean serum creatinine 371±242 mol/l) and those with end-stage renal disease on haemodialysis (n=18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0±0.4 vs 2.1±0.8 nmol/l,P<0.01), whereas plasma ANP was similar (26.9±9.7 vs 34.0±12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6±0.7 kg, corresponding to 4.5±2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r=0.43,P<0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation     

Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients

Background: Peritoneal dialysis (PD) patients have a high risk of cardiovascular mortality, which is not completely explained by conventional risk factors. Other factors related to chronic renal failure and/or dialysis treatment might lead to endothelial dysfunction, which is associated with an adverse cardiovascular outcome. One such factor is hyperhomocysteinaemia, which has a high prevalence in PD patients. Methods: A vessel wall movement detector system was used to investigate endothelium-dependent, flow-mediated and endothelium-independent, glyceryl trinitrate-induced, vasodilatation of the brachial artery in 29 PD patients and 29 control subjects. Results: Endothelium-dependent vasodilatation was markedly reduced in the PD group: 5.7±1.0% vs 10.4±1.3% in the control group (P=0.004). Endothelium-independent vasodilatation was not impaired. Plasma total homocysteine was elevated in the PD patients (45.2±6.2 &mgr;mol/l), but was not related to endothelium dependent vasodilatation. Conclusion: Chronic peritoneal dialysis patients have impaired endothelium-dependent vasodilatation, which may reflect an increased susceptibility for the development of atherosclerosis and thrombosis.      

Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients

Background: In chronic renal failure, desferrioxamine (DFO) may improve erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown. Methods: To verify whether DFO influences proliferation of erythropoietic precursors, we studied 10 patients on chronic haemodialysis, free from malignancies or other haematological diseases, iron deficiency, bone marrow fibrosis, and Al toxicity. Al accumulation was excluded by the DFO test. Peripheral blood samples were drawn for basal burst-forming unit-erythroid (BFU-E) assay. Mononuclear cells were isolated by density gradient centrifugation with Ficoll-Hypaque, and incubated for 15 days with three different experimental conditions: (a) low-dose recombinant human erythropoietin (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both DFO (167 &mgr;g/ml) and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor (sTR), haemoglobin (Hb), and haematocrit (Hct) at baseline and then every 14 days. Patients received 5 mg/kg DFO infused during the last hour of each dialysis session for 6 weeks; six patients remained in the study for an additional 6 more weeks. BFU-E assays were set up after 6 and 12 weeks of DFO therapy. Results: At baseline DFO had small effect on BFU-E proliferation (33.9±25 vs 30.4±25.9) and high-dose rHuEpo had a significant effect (45.15±27 vs 30.4±25.9, P<0.01). After 6 weeks of DFO therapy a significant increase in BFU-E proliferation was observed in all culture conditions (78.25±32 vs 30.45±25.9 standard culture, P<0.01; 110.9±30 vs45.15±27 high dose rHuEpo, P<0.01; 98.75±32 vs 45.15±27 DFO culture, P<0.01). Moreover, the increase in BFU-E proliferation was significant greater with DFO culture than standard culture (P<0.01). The same trend was found at the third BFU-E assay, performed in only six patients, when all culture conditions showed a further increase of erythroid precursor proliferation. However, the DFO culture was not significantly greater than the standard culture, while the high-dose rHuEpo was significantly greater than the DFO culture. Patients in group 1 (n=10), had a significant increase in reticulocytes (1.5±0.6 vs 1.72±0.3, P<0.01) and of hypochromic erythrocytes (HE) (5.6±5.1 vs 14.4±12.7, P<0.01), while sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decreased significantly (448±224 vs 196±215, P<0.01) and TIBC and transferrin were unchanged. Conclusions: Thus DFO increases erythroid activity by BFU-E proliferation and increases reticulocytes in haemodialysis patients. Such an effect may be related to increased iron utilization. DFO may be a useful tool for anaemic patients with good iron stores and without Al overload. Key words: desferrioxamine; erythroid progenitors; erythropoiesis; haemodialysis      

Immunocytochemical detection of a reduction in 1,25 dihydroxyvitamin D3 receptor expression in uraemic parathyroid tissue

Background. The vitamin D receptor is expressed in nuclei of parathyroid cells and plays an important role in the regulation of cell growth and parathyroid hormone secretion. A number of studies have shown reduced receptor expression in uraemic parathyroid glands but the relationship between receptor expression and renal function has not been identified. Methods. This study used archive parathyroid tissue from patients with primary adenomas, dialysis patients with diffuse hyperplasia secondary to uraemia and normal parathyroid tissue. An immunocytochemical assay with a vitamin D receptor antibody was used to identify parathyroid cells expressing receptor in their nuclei. Results. In patients with a serum creatinine ⩽110 &mgr;mol/l, 81.94%±6.5 of parathyroid cells expressed vitamin D receptor. This fell to a mean of 49.3% in two patients with a serum creatinine between 110 and 300 &mgr;mol/l and to 40.17%±8.6 in dialysis patients. Conclusion. Vitamin D receptor expression in parathyroid glands is reduced in renal failure.     

Serum aluminium level in the veneto chronic haemodialysis population: cross-sectional study on 1,026 patients

A total of 1,026 patients undergoing haemodialysis as the only chronic treatment were studied in all the dialysis units of the Veneto region, Italy. Aluminium was determined in water, dialysis fluids, and patients' serum. Aluminium mean concentration was 9.1 micrograms/l in tap water and 13.3 and 15.7 micrograms/l in bicarbonate and acetate haemodialysis fluids, respectively. Patients' serum aluminium mean level was 52.0 micrograms/l with the following frequency distribution: 59.2% below 60 micrograms/l, 25.5% between 60 and 100 micrograms, and 15.3% above 100 micrograms/l. The mean serum aluminium level was higher in patients undergoing haemodialysis with aluminium concentration in fluids over 10 micrograms/l. This was true also in patients not receiving aluminium hydroxide. Furthermore, we found higher average serum aluminium in those treated with aluminium hydroxide more than 3 g/day. No relationship was found between serum aluminium and sex, age, dialytic age, parathyroid hormone, and vitamin D treatment. Moreover, the patients with serum aluminium above 100 micrograms/l had higher serum alkaline phosphatase and lower mean cell volume values. Thus, in our haemodialysis population aluminium overloading occurred in spite of low concentration in water and fluid, and it was a result more of fluid pollution (over 10 micrograms/l) than aluminium hydroxide ingestion (over 3 g/day).     

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 21.0±4.4 &mgr;g/l; PAP 1180±1148 &mgr;g/l; F1+2 4.2±0.4 nmol/l) compared to the CU group (TAT 57.3±10.8 &mgr;g/l; PAP 1789±185 &mgr;g/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 &mgr;g/l, P <0.05), but not in the PC-PE group. In contrast, PA 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 to2.7±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 ancillary 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 improved lipid profile. These preliminary observations require confirmation by parallel group controlled studies with controlled dietary intake.     

Lipopolysaccharide-binding protein is present in effluents of patients with Gram-negative and Gram-positive CAPD peritonitis

Background: Bacterial peritonitis is a frequent complication during treatment of end-stage renal failure by continuous ambulatory peritoneal dialysis. Local host defence mechanisms including the secretion of proinflammatory cytokines by peritoneal macrophage are of particular importance in the pathogenesis of infectious complications. LPS-binding protein (LBP) and soluble CD14 (sCD14) are serum factors known to regulate the endotoxin-induced cellular immune response. However, it is still unknown whether LBP and sCD14 are also present in the peritoneal effluent of CAPD patients. Methods: Using specific immunoassays, we examined the concentration of LBP, sCD14 and the proinflammatory cytokines TNF=&agr;, IL-1{beta} and IL-6 in the dialysis effluents of 31 patients with CAPD-associated peritonitis. Twenty patients without peritonitis served as controls. Intraperitoneal LPS concentrations were determined using the limulus amebocyte lysate assay. Results: Bacterial lipopolysaccharide could be detected in 42% of the infected dialysis effluents. In comparison to controls (0.2±0.05 &mgr;g/ml), LBP was significantly elevated in both Gram-negative/LPS-positive (1.03±0.3 &mgr;g/ml) and Gram-positive infections (0.5±0.14 &mgr;g/ml) (P<0.05). No significant differences were detected concerning the intraperitoneal sCD14 levels in the three patient groups. Levels of TNF-&agr;, IL-1{beta} and IL-6 were significantly increased in the effluents of patients with bacterial peritonitis compared to non-infected controls. Moreover the respective cytokine concentrations were significantly higher in the Gram-negative/LPS-positive compared to the gram-positive bacterial infections (P<0.01). Conclusion: Our data demonstrate that LBP is significantly elevated in the dialysis effluents of patients with CAPD-associated peritonitis caused by both Gram-negative and Gram-positive bacteria and might be used as a marker of intraperitoneal infection. Moreover, our findings support the concept that LBP enhances the effects of LPS on cytokine production by peritoneal macrophages. The function of LBP in Gram-positive infection remains to be further elucidated. Key words: CAPD-associated peritonitis; cytokines; lipopolysaccharide-binding protein; macrophages; peritoneal dialysis; soluble CD14      

Treatment of renal failure in idiopathic membranous nephropathy with azathiprine and prednisolone

Background. Progressive deterioration in renal function occurs in 20-50% of patients with idiopathic membranous nephropathy (IMN). Several treatment regimens have been used to reverse this with varying effect and toxicity. Methods. Thirteen patients (10 males, 3 females, median age 56 years) with IMN and progressive renal failure were treated with oral prednisolone 20-60 mg/day and azathiprine 1.3-2.7 mg/kgBW/day. All patients were followed up for a minimum of 2 years with a median follow-up of 73 months (range 24-103 months). Results. Ten patients responded to treatment with a fall in serum creatinine and renal function stabilized in the remainder. Two patients relapsed, one of whom responded to an increase in immunosuppression, the other is now on dialysis. Proteinuria has significantly reduced in 10 patients, and only four patients still have nephrotic-range proteinuria. Mean (±SE) peak pre-treatment serum creatinine of 229 (±161) &mgr;mol/l and urinary protein of 11.8 (±1.8) g/24 h have fallen to 163 (±65) &mgr;mol/l and 3.25 (±1.0) g/24 h after 12 months treatment (P=0.005, Wilcoxon matched pairs test). Immunosuppressive treatment has been successfully withdrawn in four patients after intervals ranging from 12 to 60 months. Adverse effects, which occurred in 10 patients, have been mild and have not led to treatment withdrawal though dose reductions have been necessary in some patients. Conclusions. Oral prednisolone and low-dose azathioprine is an effective therapy for progressing renal failure due to IMN, and induces remission of nephrotic syndrome. Side-effects are less than other immunosuppressive regimens.     

The absorption of iron is disturbed in recombinant human erythropoietin-treated peritoneal dialysis patients

Background. Intravenous iron supplementation is often necessary in recombinant human erythropoietin (r-HuEPO)-treated haemodialysis (HD) patients, but rarely in r-HuEPO-treated peritoneal dialysis (PD) patients. This may be due to differences in iron absorption or blood loss. Method. Iron absorption (whole-body counting after ingestion of a radiolabelled iron test dose) and iron metabolism were compared in eight iron-replete r-HuEPO-treated PD patients (serum ferritin 100-500 &mgr;g/l) and 68 healthy iron-replete controls (sufficient iron in bone marrow specimen). Results. Mucosal uptake (13.4±9.8), mucosal transfer (0.34±0.18) and iron retention (4.9±4.0) in PD patients was significantly lower than in controls (42.9±18.8%, P<0.0001, 0.63±0.18, P<0.0001, and 28.0±16.7%, P<0.0001). Conclusion. Iron absorption is impaired in PD patients, as we have shown previously for HD patients. One reason for higher iron needs in HD patients may be higher blood losses due to the dialysis procedure and blood sampling for laboratory tests.     

Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in haemodialysed patients?

Background. Patients with end-stage renal failure undergoing haemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) were demonstrated in plasma of uraemic patients, indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients. Methods. MDA and 4-hydroxynonenal (HNE) were measured in three groups of patients undergoing HD: group I comprised eight patients with a blood haemoglobin (Hb) <10 g/dl (mean Hb=8.1±1.3 g/dl), and group II were eight patients with a Hb <10 g/dl (mean Hb=12.4±1.9 g/dl); none of these 16 patients had been treated with human recombinant erythropoietin (rHuEpo). Group III comprised 27 patients with a mean Hb of 10.5±1.6 g/dl after long-term rHuEpo treatment. Results. Mean plasma concentrations of both MDA and HNE were significantly higher (P<0.0001) in all 43 HD patients than in 20 healthy controls (MDA 2.85±0.25 vs 0.37± &mgr;M, HNE 0.32± vs 0.10±0.01 &mgr;M). Comprising the three groups, it was shown that HD patients with a Hb <10 g/dl had significantly higher plasma levels of LPO products (MDA 3.81±0.86 &mgr;M, HNE 0.45±0.07 &mgr;M) than HD patients with a Hb > 10 g/dl (MDA 2.77±0.58 &mgr;M, HNE 0.25±0.05 &mgr;M), and than HD patients treated with rHuEpo (MDA 2.50±0.12 &mgr;M, HNE 0.29±0.03 &mgr;M). Furthermore, an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen (r=0.62, P<0.0001). Conclusion. Radical generation in HD patients might be caused in part by renal anemia itself. Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration. Keywords: erythropoietin; haemodialysis; HNE; lipid peroxidation; MDA; renal anaemia      

Long-term experience with an ultrapure individual dialysis fluid with a batch type machine

Background. This paper discusses long-term experience with a specific type of dialysis equipment which has been used more than 15 years without variation. The system was designed to allow easy individualization of dialysis fluid composition and to deliver dialysate of the highest hygienic quality. Methods. Data from 399 patients covering the period from 1971 onwards were analysed retrospectively. Survival probabilities were estimated by the Kaplan-Meier method and the median number of days in hospital was calculated. Additional data collected from patient subgroups included serum albumin level, erythropoietin requirement and antihypertensive treatments. Kt/V and PCR from one subgroup were computed using the formulae of Daugirdas and Depner. Results. The estimated survival probability after 5 years for all patients was 59.1% (95% CI:52.6-65.6%). The main risk factors from the available covariables were age and IDDM. The cumulative incidence of carpal tunnel syndrome after 10 years of dialysis was estimated as 7% (95% CI: 0-14%). Data from the subgroups revealed that 82% of the patients had serum albumin levels >4.0 g/dl, 65% of the patients received no antihypertensive drugs and 39% received erythropoietin (37±28 units/kg bw/week) to correct dialysis anaemia (haemoglobin level=98±8 g/l). Average Kt/V was 1.21±0.17, PCR was 1.10±0.22 g/kg/day. Conclusions. The setup described permits individualized therapy of high quality. The high serum albumin values and our very low incidence of carpal tunnel syndrome underline the importance of water and dialysate quality.     

A comparison of solute clearance and ultrafiltration volume in peritoneal dialysis with total or fractional (50%) intraperitoneal volume exchange with the same dialysate flow rate

Background: The most efficient way to perform automated peritoneal dialysis (APD) has not yet been defined. Tidal peritoneal dialysis (TPD) has been claimed to be more efficient than traditional intermittent peritoneal dialysis (IPD), but few comparative studies have been done keeping dialysate flow the same in the two treatment techniques. Method: Six patients were treated with 10, 14 and 24 litres total dialysis fluid volume during 9 h (flow rate 18,5, 25.9 and 44.4 ml/min), receiving the treatments both as IPD and TPD. Glucose concentration in the fluid was held constant during all treatments. Transperitoneal clearances (ml/min) for urea, creatinine and uric acid and ultrafiltration volume was calculated, and comparisons made between TPD and IPD. The total intraperitoneal dwell time was calculated for each treatment session. A peritoneal equilibration test was also done for each patient. Results: The ratio of the creatinine concentration in dialysate to the concentration in plasma at 4 h obtained with the peritoneal equilibration test (PET) averaged 0.77 (range 0.69-0.82). Urea clearance was higher for IPD than for TPD with 10 litres: 14.3±2.4 and 13.3±2.7 (P=0.0092). For 14 and 24 litres urea clearance for IPD and TPD was 17.9±2.3 and 15.9±3.5 (n.s.) and 20.9±3.6 and 19.9±5.6 (n.s) respectively. Creatinine clearance was higher for IPD than for TPD with 10 litres: 9.6±1.3 and 8.9±1.3 (P=0.0002). For 14 and 24 litres creatinine clearance for IPD and TPD was 11.0±0.7 and 9.9±2.0 (n.s.) and 12.3±1.2 and 12.4±2.2 (n.s.) respectively. Uric acid clearance was higher for IPD than for TPD with 10 litres: 8.4±1.3 and 7.7±1.0 (p=0.0054). For 14 and 24 litres uric acid clearance for IPD and TPD was 9.4±1.7 and 8.9±2.2 (n.s.) and 11.3±2.9 and 10.6±2.6 (n.s.) respectively. IPD gave significantly higher ultrafiltration volume (ml) than IPD for both 10 and 14 litres: 944±278 and 783±200 (P=0.0313) and 1147±202 and 937±211 (P=0.0478). For 24 litres there was no significant difference between IPD and TPD: 1220±224 and 1253±256. Conclusion: With the lowest dialysate flow rate (18.5 ml/min), solute clearance and ultrafiltration volume was higher on IPD than on TPD. With the intermediate flow rate (25.9 ml/min) the ultrafiltration volume was higher on IPD, but no difference was found for solute clearance. With the highest flow rate (44.4 ml/min) there as no difference neither for ultrafiltration nor for solute clearance.     

Iron supplementation in haemodialysis - practical clinical guidelines

Background. The aim of this prospective study was to test a new protocol for iron supplementation in haemodialysis patients, as well as to assess the utility of different iron metabolism markers in common use and their 'target' values for the correction of iron deficiency. Methods. Thirty-three of 56 chronic haemodialysis patients were selected for long-term (6 months) i.v. iron therapy at 20 mg three times per week post-dialysis based on the presence of at least one of the following iron metabolism markers: percentage of transferrin saturation (%TSAT) <20%; percentage of hypochromic erythrocytes (%HypoE) >10% and serum ferritin (SF) <400 &mgr;g/l. Reasons for patient exclusion were active inflammatory or infectious diseases, haematological diseases, psychosis, probable iron overload (SF ⩾400 &mgr;g/l) and/or acute need of blood transfusion mostly due to haemorrhage and change in renal replacement treatment. Results. More than half (51.8%) of the patients of our dialysis centre proved to have some degree of iron deficiency in spite of their regular oral iron supplementation. At the start of the study the mean haemoglobin was 10.8 g/dl and increased after the 6 months of iron treatment to 12.8 g/dl (P<0.0001). The use of erythropoietin decreased from 188 units/kg/week to 84 units/kg/week. The criterion for iron supplementation with the best sensitivity/specificity relationship (100/87.9%) was ferritin <400 &mgr;g/l. Patients with ferritin <100 &mgr;g/l and those with ferritin between 100 &mgr;g/l and 400 &mgr;g/l had the same increase in haemoglobin but other parameters of iron metabolism were different between the two groups. Conclusions. Routine supplementation of iron in haemodialysis patients should be performed intravenously. Target ferritin values should be considered individually and the best mean haemoglobin values were achieved at 6 months with a mean ferritin of 456 &mgr;g/l (variation from to 919 &mgr;g/l). The percentage of transferrin saturation, percentage of hypochromic erythrocytes and ferritin <100 &mgr;/l, were not considered useful parameters to monitor routine iron supplementation in haemodialysis patients. No significant adverse reactions to iron therapy were observed. Keywords: erythropoietin; ferritin; haemodialysis; iron; intravenous