Exacerbation of Aluminium Encephalopathy After Treatment with Desferrioxamine

Two haemodialysis patients with aluminium encephalopathy developeddramatic deteriorations of their neurological symptoms afterinitiation of desferrioxamine (DFO) therapy. Both patients weretreated with relatively large doses of DFO (1 g and 2 g pertreatment). In the first case, paranoid delusions, visual hallucinations,seizures and deteriorating speech followed each dialysis treatmentwith DFO. The second patient experienced increasing confusion,decreasing short-term memory, and deterioration in speech. Inboth cases the neurological symptoms regressed after decreasingor discontinuing the DFO. These patients demonstrate the potentialdangers of using high doses of DFO. The pathogenesis of theexacerbation is not well understood but, may not simply be dueto the result of elevated plasma aluminium levels after DFOtherapy. We argue in this communication for reducing DFO inpatients with aluminium encephalopathy to doses of 1 g threetimes per week to ensure adequate treatment of aluminium encephalopathywhile minimising the risk of exacerbation from overzealous DFOadministration.     

The Use of Intravenous and Intraperitoneal Desferrioxamine in Aluminium Osteomalacia

A 32-year-old male with aluminium osteomalacia was changed fromhaemodialysis to chronic ambulatory peritoneal dialysis (CAPD)because of vascular access problems. Desferrioxamine (6 g) wasadministered intravenously on a once-weekly basis and the quantityof aluminium removed from each dialysate was calculated weekly.Aluminium concentration was estimated using the electrothermalatomic absorption spectrophotometer. The total aluminium removedafter one week was 191 µmol, giving a clearance for aluminiumof 4.2 ml per mm. Subsequently intraperitoneal desferrioxamine0.5 g per dialysate was administered to a total dose of 6 gand the cumulative aluminium loss was 134.1 µmol givinga clearance of 3.1 ml per mm. The weekly loss of aluminium fromdialysate when no desferrioxamine was administered was 58.3µmol, giving a clearance of 2.5 ml per mm. This is thefirst documented comparison of clearance rates for aluminiumbetween CAPD alone, CAPD plus intravenous desferrioxamine andCAPD plus intraperitoneal desferrioxamine.     

C-Reactive Protein in Haemodialysis Patients With Dialysis Arthropathy

Increased plasma C-reactive protein was found in one-third of99 patients on maintenance haemodialysis and there was a significantcorrelation between C-reactive protein and years on haemodialysis.Patients with dialysis arthropathy had a significantly highermean C-reactive protein than the patients with no joint symptoms.Our results susggest that chronic inflammatory reactions occurin long-term haemodialysis patients and that dialysis arthropathymay have an inflammatory basis.     

Human Recombinant Erythropoietin in Anaemic Patients on Maintenance Haemodialysis. Secondary effects of the Increase of Haemoglobin

Twelve anaemic patients on haemodialysis were treated with recombinanthuman erythropoietin, starting with 72 IU/kg/week. The dosewas doubled after 2 weeks until an increase of 2 g/dl of haemoglobinwas observed. The effects on various parameters were studiedduring a 3-month period. Haemogiobin increased from 6.70±0.74to l0.49±1.04g/dl (mean±SD, P<0.00l), potassiumfrom 5.51±0.50 to 6.06±0.65mmol/1 (P<0.005),phosphate from 1.78±0.40 to 2.17±0.4Ommol/1 (P<0.001)and the calcium phosphorus product from 4.3 to 5.2 (P<0.001)Three patients developed marked periarticular inflammation dueto calcified deposits with a high calcium-phosphorus productof 6.8. An increase in arterial blood pressure was observedin three previously well-controlled hypertensive patients, oneof whom developed hypertensive encephalopathy. We conclude thatrecombinant human erythropoietin is very effective in treatingthe anaemia of end-stage renal failure on haemodialysis. Regularestimations of serum potassium and phosphate are mandatory.In hypertensive individuals a further increase in blood pressureis possible.     

Quality of Life in Turkish Haemodialysis Patients

The aim of the study was to assess quality of life (QOL) in Turkish haemodialysis patients and to identify related socio-demographic and clinical variables. To measure QOL 100 patients completed SF-36 during regularly scheduled haemodialysis. We found that patients’ QOL was substantially impaired. Age was negatively related to physical components of QOL. Duration of haemodialysis was negatively correlated with most of QOL dimensions. EPO treatment, education on disease and haemodialysis, and compliance to prescribed diet had great positive effects on QOL. Among the factors we have found to be related with the QOL in this study, probably the most important were education on disease and haemodialysis, and compliance to prescribed diet, in which we have influence, as nurses, on improving the QOL in patients receiving haemodialysis. The priority of renal nursing services should therefore be addressed to provide support in these areas.     

Carnitine and Weakness in Haemodialysis Patients

Weakness in haemodialysis patients has been attributed to severalfactors including carnitine deficiency. Malnutrition, neuropathy,uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced musclepower compared with a normal population, and to be malnourishedby dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle,with an excess of esterified carnitine in both plasma and muscleand diminished free plasma carnitine. Muscle biopsy showed nofeatures of carnitine deficiency and electromyography showeda non-specific neuropathy with additional myopathic changesin some. Dietary supplementation with L-carnitine (2 g/day)for 6 weeks in a placebo-controlled trial showed a redistributionof carnitine fractions but no subjective or objective improvementin muscle function. There was no improvement in the plasma lipidprofile. The weakness of haemodialysis patients is multifactorial. Wehave not demonstrated total carnitine depletion in either muscleor plasma, and oral supplementation of L-carnitine has no demonstrableeffect in this group.     

Silicone-Induced Hypercalcaemia in Haemodialysis Patients

Silicone spallation from the roller-pump insert in dialysisblood lines leads to the accumulation of silicone in haemodialysispatients, which in turn leads to a foreign-body reaction withgranuloma formation. We have studied two patients in whom documentedsilicone accumulation has been associated with both granulomaformation and significant, persistent hypercalcaemia. In bothpatients plasma levels of immunoreactive parathyroid hormoneand 1,25-dihydroxyvitamin D were low or undetectable. In onepatient, hypercalcaemia responded only partially to corticosteroids,but completely to naproxen. Both patients were changed to silicone-freeblood lines and their hypercalcaemia subsequently resolved.The results indicate that in some haemodialysis patients, siliconeaccumulation and granuloma formation may lead to hypercalcaemiathat is independent of 1,25-dihydroxyvitamin D, and that mayinstead reflect altered prostaglandin metabolism.     

Effect of Haemodialysis on Upper Gastrointestinal Tract Pathology in Patients With Chronic Renal Failure

Upper gastrointestinal tract pathology observed at autopsy in94 patients with end-stage renal disease (GFR<10 ml/min)was analysed retrospectively. To better evaluate the effectof haemodialysis on this pathology, the chronic renal failurepatients were subdivided into three groups: 19 patients whohad died before haemodialysis treatment could be undertaken(group I), 21 patients who had died during the first month (groupII), and 54 patients who had died after at least one month ofhaemodialysis treatment (group III). The results revealed thatthe number of patients with upper gastrointestinal tract pathologywas significantly higher in groups I and II (58% and 57% respectively)as compared to group III (31%) and controls (35%). No differencecould be demonstrated between group III and controls. The mostprevalent lesions observed were gastritis, followed by gastricand peptic ulcers. The incidence of this pathology appearedto decline as the duration of dialysis therapy increased. Mortalitycaused by upper gastrointestinal tract pathology remained highduring the first two years of treatment in group III, despitea smaller incidence of upper tract lesions. This was explainedby a relatively higher proportion of haemorrhage.     

Topical Anaesthesia for Fistula Cannulation in Haemodialysis Patients

The use of a local anaesthetic cream (EMLA; Astra) for arteriovenousfistula cannulation was compared to placebo in a double-blindrandomised manner in 26 patients undergoing chronic haemodialysiswho were currently using injections of lignocaine. The EMLAcream was highly effective compared to placebo (P<0.0Ol)on visual analogue and verbal rating scales as well as easeof venepuncture (P < 0.01). It also gave more pain reliefand improved the ease of venepuncture compared to lignocaineinjections. Patients expressed a strong preference for the EMLAcream, which has advantages that outweigh the cost and conveniencefactors.     

Critical role of iron overload in the increased susceptibility of haemodialysis patients to bacterial infections. Beneficial effects of desferrioxamine

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.     

The Effect of L-carnitine on Lipid Metabolism in Patients on Chronic Haemodialysis

Twenty-one patients (median 49 years; range 20–72 years)on chronic haemodialysis (median: 54 months; range 16–154months) were examined in a clinical controlled trial for theeffect of carnitine on hyperlipoproteinaemia. Initial valuesof serum carnitine were within the normal range. Carnitine wasadded to the dialysis fluid to a final concentration of 100µmol/l. The trial was carried out for 6 months, and theserum of fasting patients was analysed at monthly intervalsfor carnitine, triglycerides, HDL-cholesterol, LDL-cholesteroland apolipoprotein A and B. The loss of carnitine to the dialysisfluid also was examined, as was the retained amount in thosereceiving carnitine. We could not confirm the findings of others[1,2,3,4,5] that carnitine produces lowering of serum triglyceridesand increases of serum HDL-cholesterol. The study was extended for another year with ten patients; however,no change was observed in the lipid pattern.     

Lipoprotein Abnormalities in Chronic Haemodialysis Patients

Measurement of lipids, apolipoproteins A-I, A-II, B, C-III,Lp(a) and cholesterol, phospholipids, apo C-III in lipoproteinwith and without apolipoprotein B was made in 49 patients (18women and 31 men; mean age 50±15 years) undergoing maintenancehaemodialysis for chronic renal failure. A group of 49 healthypeople, matched for sex and age, acted as controls. In the haemodialysis group, special attention was placed uponthe comparison of patients who had evident cardiovascular alterations(n=17) with the residual group (n=32). The concentration ofapo C-III in apolipoprotein B containing lipoproteins was statisticallyhigher in the patients with arterial disease than in the remainingsub jects, whereas the ratio apo C-III from Lp no B/apo C-IIIfrom Lp B was decreased. Compared to controls, haemodialysispatients had significantly higher values of triglycerides, apolipoproteinsC-III, Lp(a), and apolipoprotein C-III from apolipoprotein B-containinglipoproteins (LpB); in contrast, concentrations of phospholipidsand cholesterol from lipoproteins without apolipoprotein B (Lpno B) and apolipoprotein A-II were significantly reduced inpatients. Discriminant analysis indicated that the levels ofapolipoprotein C-III and apolipoprotein C-III from LpB werethe best indicators of deranged lipid transport in patientswith chronic renal failure. Our data suggest that chronic haemodialysis patients tend toexhibit qualitative abnormalities of serum apolipoprotein-Btriglyceride rich particles containing apolipoprotein C-IIIor (a).     

Increase in Serum Magnesium Level in Haemodialysis Patients Receiving Sevelamer Hydrochloride

Background: Clinical studies have shown that sevelamer hydrochloride improves lipid profiles and attenuates the progression of the cardiovascular calcifications in haemodialysis patients. It is known that both of these properties are associated with increased magnesium levels. The effect of sevelamer on serum magnesium level is not well documented. The aim of this study was to determine the effects of sevelamer treatment on serum magnesium in haemodialysis patients and to assess the association of magnesium levels with lipid profiles and intact parathyroid hormone (iPTH). Methods: Phosphate binders were discontinued during a two week washout period. Forty-seven patients, whose serum phosphate was greater than 6.0 mg/dl at the end of washout, received sevelamer hydrochloride for eight weeks. The patients were then washed off sevelamer for another two weeks. Results: Mean serum phosphorus concentration declined from 7.5 ± 1.3 to 6.4 ± 1.2 mg/dl (P < 0.001), mean serum magnesium levels increased from 2.75 ± 0.35 to 2.90 ± 0.41 mg/dl (P < 0.001) and median serum iPTH levels decreased from 297 to 213 pg/ml (P=0.001) during the eight weeks of sevelamer treatment. After the two week post-treatment washout phosphorus levels increased to 7.3 ± 1.3 mg/dl (P < 0.001), magnesium levels were reduced to 2.77 ± 0.39 mg/dl (P < 0.001) and iPTH levels increased to 240 pg/ml (P=0.012). No change was observed in serum calcium levels during the sevelamer treatment period and the subsequent washout period. The mean decline in total and low density lipoprotein (LDL) cholesterol during sevelamer treatment was 16.3 and 28.3 (P < 0.001), respectively. The mean increase in high density lipoprotein (HDL) cholesterol and in apolipoprotein A1 was 2.9 ± 5.8 mg/dl (P=0.004) and 6.8 ± 11.1 mg/dl (P=0.001), respectively. Multivariate analysis showed that the rise in serum magnesium concentration significantly correlated with reductions in iPTH levels (r=−0.40, P=0.016), but did not have any significant correlation with the changes in lipid profiles. Conclusions: Our findings indicate that patients on haemodialysis receiving sevelamer have a significant increase in serum magnesium concentrations. This increase in serum magnesium is associated with reduction in iPTH levels. The changes in lipid profiles of these patients however are not related to changes in serum magnesium levels.     

Correction of anaemia of chronic renal failure with recombinant human erythropoietin: safety and efficacy of one year's treatment in a European multicentre study of 150 haemodialysis-dependent patients

One hundred and fifty patients undergoing regular haemodialysis for end-stage renal failure entered a trial of treatment for anaemia with recombinant human erythropoietin (r-HuEPO). At data cut-off 37 patients (24.6%) had dropped out for various reasons; most of them (n = 22) discontinued because of kidney transplantation (after 3-17 months of treatment). The initial dose was 24 U/kg i.v. thrice weekly, with subsequent dose escalations after a minimum of 2 weeks if the haemoglobin (Hb) was less than 10% above the pretreatment baseline. One hundred and forty-three patients who were eligible for efficacy analysis achieved an Hb increase of greater than or equal to 2 g/dl, and all 139 patients eligible for 'full response' analysis (Hb between 10 and 12 g/dl) were dose titrated to reach this arbitrarily defined optimal range. Patients' response to r-HuEPO treatment was independent of age, weight, nephric state or duration of dialysis treatment. To maintain the Hb within the range of 10-12 g/dl during 1 year's treatment (n = 96) a median weekly r-HuEPO dose of 200 U/kg (range 150-300) divided into one, two, or three administrations appeared to be adequate. This maintenance dose depends slightly on the patient's baseline Hb. The study provides evidence that long-term treatment with r-HuEPO is safe. In 48 patients (of whom 12 had no history of hypertension) elevation of blood pressure required additional treatment, which was effective in all but one who was withdrawn from the study. Four patients had seizures and one suffered hypertensive encephalopathy without convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Ultrafiltration on Plasma Concentrations of Atrial Natriuretic Peptide in Haemodialysis Patients

We have investigated the influence of body fluid volume statuson plasma levels of immunoreactive atrial natriuretic peptide(irANP) in eight uraemic patients on chronic haemodialysis,including two diabetics with severely impaired reflex controlof the heart. IrANP was significantly higher in volume-expandeduraemic patients (36±16 pg/ml) than in a group of sevenage and sex-matched normal subjects (14±2 pg/ml), andfell consistently, approaching the normal range after the removalof 2.0–4.3 litres of isotonic plasma ultrafiltrate (byisolated ultrafiltration). Plasma levels of the hormone werestrictly related to right atrial pressure. The irANP responseto ultrafiltration in the two diabetics was similar to thatof the other uraemic patients. The results suggest that theelevated irANP levels found in volume-expanded uraemic patientsdepend largely on fluid overload per Se. The preserved irANPresponse to ultrafiltration of the two diabetics with severeautonomic neuropathy indicates that in chronic renal failureirANP secretion may be regulated independently from autonomicinfluences.     

维持性血透患者血清NGAL水平与体内铁存储的相关性研究

目的:探讨在维持性血液透析患者,其血清NGAL(中性粒细胞明胶酶相关载脂蛋白)水平与体内铁存储的关系。方法:从2010年10月开始,我们纳入我院血液透析患者人数150例,同时纳入50例健康人为对照。收集患者及健康对照人群的人口学资料、相关的临床和生化学资料,透析前后NGAL及透析前CRP、转铁蛋白饱和度、铁蛋白、血清铁、转铁蛋白等。做透析前血清NGAL与CRP、转铁蛋白饱和度、铁蛋白、血清铁、转铁蛋白相关性分析。评估NGAL水平在判断体内铁存储的价值。结果:(1)血液透析患者其血清NGAL透析前水平为(445.45±50.34)ng/ml,透析后为(369±50.34)ng/ml,差异有统计学意义(P<0.05)。(2)血液透析患者其血清NGAL水平与CRP、spKt/V、TSAT等指标均有正相关关系(P<0.05),但与铁蛋白、血清铁、转铁蛋白无明显线性关系(P>0.05)。在多元线性回归模型中,NGAL水平与CRP、spKt/V、TSAT有相关关系(P<0.05)。(3)ROC曲线表明,NGAL水平较铁蛋白更好的反映体内铁存储情况,但差异无统计学意义(P>0.05)。结论:在血液透析患者,血清NGAL与spKt/V、CRP、TSAT有不同程度的正相关。血清NGAL能较好的反映体内铁存储情况。     

Plasma Oxalate Concentration, Oxalate Clearance and Cardiac Function in Patients Receiving Haemodialysis

Pre-dialysis plasma oxalate concentration was measured in across-sectional study of 75 patients receiving maintenance haemodialysis.The aims of this study were to enable formulation of hypothesesregarding the determinants of plasma oxalate concentration andto allow preliminary examination of the possibility that hyperoxalaemiaconfers an increased risk of cardiac and vascular disease evenin the absence of primary hyperoxaluria. Plasma oxalate concentrationranged between 7 and 76 µmol/l, mean (SD) 34.6 (18.1)µmol/l(normal range < 0.8–2.0 µmol/l). Significantcorrelations were found between plasma oxalate concentrationand plasma creatinine, duration of dialysis, current dose ofascorbic acid, and serum phosphate, and each of these variablesretained significance on multiple linear regression. Oxalate clearance across a 1 m² hollow-fibre Cuprophan dialyser,at 500 ml/min dialysate flow and blood flow between 175 and225 ml/min, was measured 1 h after commencement of dialysis(n=19). Mean (SD) clearance was 96.5 (27.0) ml/min. No significant association was found between self-reported maximumwalking distance or the occurrence of symptons of cardiac failureand plasma oxalate concentration. No relationship was foundbetween plasma oxalate concentration and electrocardiographicconduction disturbances (n=8) ‘major’ ST/T wavechanges (n=22), ‘minor’ ST/T wave changes (n=49).Plasma oxalate was significantly greater in patients with radiologicallydetectable calcification of medium-sized arteries than in thosewithout calcification, but duration of dialysis was also significantlylonger in these patients. Routine haemodialysis results in marked hyperoxalaemia, whichmay be exacerbated by ascorbate supplementation. Oxalate clearanceis similar to that of other small molecules such as creatinineand phosphate. No relationship was demonstrated between hyperoxalaemiaand symptoms of cardiac disease. The question of whether hyperoxalaemiaconfers an increased risk of vascular calcification will onlybe answered definitively by prospective studies.     

Changes in Blood Acetaldehyde Concentrations During Acetate Haemodialysis

Hyperacetataemia during acetate haemodialysis has been associatedwith the development of a variety of unpleasant symptoms, althougha direct toxic effect of acetate is hard to prove. Acetaldehyde,which is produced during the metabolism of ethanol to acetate,has various toxic effects including some of those reported duringacetate dialysis such as nausea, headache and palpitations.Using a novel, recently developed method we studied blood acetaldehydeconcentrations during acetate dialysis in 15 patients and foundsignificant increases in five, with a mean peak value in thesepatients of 1.36 µmol/l (normal <0.4 µmol/l).These five patients also developed high blood acetate concentrationsduring a subsequent acetate dialysis and showed a significantcorrelation between blood acetaldehyde and acetate concentrations(r=0.55, P<O.05). Blood acetaldehyde did not change duringbicarbonate dialysis in these patients. Our results suggestthat significant accumulation of acetaldehyde may occur duringacetate dialysis, especially in those patients whose metaboliccapacity for acetate is somehow impaired, and that acetaldehydemay contribute to some of the symptoms previously ascribed to‘acetate’ intolerance.     

The Effects of Zero Magnesium Dialysate and Magnesium Supplements on Ionised Calcium Concentration in Patients on Regular Dialysis Treatment

The effect of oral magnesium carbonate aluminium hydroxide onserum ionised calcium, total calcium, aluminium and magnesium,was assessed in 31 patients with chronic renal failure, duringand after one haemodialysis. The behaviour of ionised calcium and total calcium was the samein both groups. Each showed a slight fall during dialysis, whichwas not significant. Serum total calcium was 0.2–0.3 mmol/l(0.8–1.2 mg/dl) greater throughout the period of dialysisin the group taking aluminium hydroxide. Serum magnesium andaluminium were both lower in the group treated with magnesiumcarbonate. In the group taking magnesium carbonate, serum magnesium concentrationsfell markedly during dialysis, but otherwise were maintainedwithin the reference range by the use of a magnesium-free dialysate.These results show the effectiveness of magnesium carbonateoral phosphate-binding agents and zero magnesium dialysate inreducing serum aluminium without affecting the behaviour ofserum calcium fractions during dialysis.