Long-term use of the low molecular weight heparin tinzaparin in haemodialysis.

Fifty-two patients with chronic renal failure undergoing hospital haemodialysis were given a single bolus dose of tinzaparin (Innohep, Leo Laboratories, UK) into the arterial side of the dialyser, for up to 43 consecutive dialyses. The mean tinzaparin dose at the beginning was 2,139 IU anti-Xa and at the end 2,186 IU anti-Xa. Overall, tinzaparin proved a satisfactory anticoagulant for 1,370 (96.0%) out of 1,427 dialyses. Significant clot formation was prevented in 1,326 (92.8%) out of 1,429 dialyses. The clinically effective dose was associated with a mean plasma anti-Xa activity 1 h after dosing of 0.4 IU/ml and suppressed fibrinopeptide A formation for up to 4 h. Bleeding, from the skin or mucous membranes, was recorded at 27 (1.9%) of 1,408 dialyses. Prolonged fistula bleeding on completion of dialysis was recorded on only 20 occasions. Other haemorrhagic events included haematemesis, bruising and subconjunctival haemorrhage (each in 1 patient) and epistaxis (2 patients). Three patients died during the study of causes considered unrelated to tinzaparin therapy, myocardial infarction (2 patients) and multiple myeloma. Other adverse events reported included vomiting (3 patients) and hypotension (3 patients). Three patients ceased treatment due to haematemesis, prolonged bleeding from fistula puncture and thrombosis of the arteriovenous access, respectively. A small, but statistically significant, increase within the normal reference range was recorded in the mean values for aspartate aminotransferase and alanine aminotransferase.

Dialysis at home in the west of Scotland: a comparison of hemodialysis and continuous ambulatory peritoneal dialysis in age- and sex-matched controls.

OBJECTIVE: To audit the outcome of patients treated at home by hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective comparison of nondiabetic hemodialysis patients with age- and sex-matched nondiabetic patients treated by CAPD. SETTING: Renal Units, Stobhill General Hospital and Western Infirmary, Glasgow, providing the home dialysis service for the West of Scotland. PATIENTS: Between 1982 and 1988, 139 hemodialysis patients starting treatment at home, compared with 139 matched patients starting CAPD over the same time period. MAIN OUTCOME MEASURES: Patient characteristics and cardiovascular risk factors at the start of home treatment. Patient and technique survival with both forms of dialysis. RESULTS: Patients selected for home hemodialysis were less likely to be smokers (p < 0.02) and to have electrocardiographic evidence of ischemia or left ventricular hypertrophy (p < 0.05) than patients treated by CAPD. Patient survival and technique survival (excluding death and renal transplantation) at 3 years were 93.8% versus 86.2% (p < 0.05) and 94.2% versus 80.8% (p < 0.04) for hemodialysis and CAPD, respectively. Cardiovascular events were responsible for the majority of deaths in both groups, but there was a greater proportion of deaths from other causes in patients treated by CAPD. There was no significant difference in the transplantation rate between the two treatment groups. CONCLUSIONS: Home dialysis is an effective method of renal replacement treatment for patients with end-stage renal disease. The results of hemodialysis are superior to CAPD, but this may be partly due to selection bias.

Plasma oxalate in patients with chronic renal failure receiving continuous ambulatory peritoneal dialysis or hemodialysis.

Plasma oxalate was measured in 20 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and 20 patients receiving hemodialysis (HD). All patients had levels well above the reference range of less than 2.0 to 5.0 mumol/L (less than 0.18 to 0.44 mg/L), the medians being 34 mumol/L (2.99 mg/L) and 42 mumol/L (3.70 mg/L) for the two groups, respectively. Plasma oxalate did not differ significantly in the two groups. Plasma oxalate was not influenced by the number of months patients had received dialysis treatment, but a significant correlation was found between oxalate and creatinine in the 40 patients studied (P less than 0.02, r = 0.38). Predialysis oxalate levels were reduced by approximately 60% following HD, but returned to 80% of the predialysis levels within 24 hours and 95% within 48 hours. Oxalate levels did not differ significantly in samples taken before, during, and after exchanges of CAPD fluid. That the patients treated with CAPD did not have higher oxalate levels than the HD group suggests that the continuous nature of the former treatment compensates for the lower oxalate clearance by the peritoneum. The reported higher risk of oxalosis associated with intermittent peritoneal dialysis has led to a similar risk being postulated for CAPD; however, the present study indicates that if such a risk exists, it cannot be explained by higher levels of oxalate or ionized calcium in these patients.

Ranitidine suppresses aluminium absorption in man.

1. Intragastric pH monitoring was performed before and after the single-blind administration of ranitidine or placebo (saline) in eight healthy subjects and four patients with end-stage renal disease who were on regular haemodialysis. 2. The subjects were studied on two occasions and were given aluminum hydroxide (1185 mg) orally 90 min after the administration of ranitidine or saline. 3. Plasma aluminum concentrations and, in normal men, urinary excretion of aluminum were monitored before and after the oral aluminum load. 4. Intragastric pH increased significantly with ranitidine but not with placebo (P less than 0.001). Urinary aluminum excretion increased significantly after the administration of aluminum hydroxide during the placebo phase (P less than 0.001) but not during the ranitidine phase. Plasma aluminium concentrations were higher in the patients with renal failure than in the normal subjects (P less than 0.05), but were unchanged in both groups after the oral aluminium load. 5. This study shows that gastric pH is an important factor in the modulation of aluminum absorption in man, and indicates that reducing gastric acid secretion with ranitidine may reduce the toxicity of orally administered aluminium compounds.

The effect of vitamin C intake on plasma oxalate in patients on regular haemodialysis.

Plasma oxalate was measured on two occasions in 18 patients with end-stage renal failure on regular haemodialysis treatment: once while on a routine dose of vitamin C (100 mg/day) and subsequently after 2 weeks administration of a larger dose of vitamin C (500 mg/day). Pre- and post-dialysis concentrations were all markedly increased, reflecting the reduced glomerular filtration rate of end-stage renal failure. Both pre- and post-dialysis oxalate increased significantly following the increase in ascorbate dose but there was no significant correlation between plasma oxalate and ascorbate results. Considerations governing dosage of vitamin C in patients with chronic renal failure are discussed.

A simple, rapid assay for plasma oxalate in uraemic patients using oxalate oxidase, which is free from vitamin C interference.

An enzymatic assay for the determination of oxalate in plasma was developed which is specific, simple, rapid and requires no specialised equipment; interference from vitamin C was removed by incubation of acidified plasma ultrafiltrate with ascorbate oxidase prior to oxalate estimation. Recoveries were 93 +/- 11% and the inter-batch coefficient of variation for 31 determinations at an oxalate level of 24 mumol/l was 10%. The assay is linear up to 300 mumol/l with a detection limit of 2 mumol/l. The reference range, based on results from 25 healthy volunteers, was defined as less than 2-5 mumol/l which is similar to levels established for the in vivo isotope dilution technique. The assay has an added advantage over the latter method, which requires a urine collection, in that it can be applied to plasma from anuric patients. A linear correlation (r = 0.68, p less than 0.001) was found between plasma oxalate and serum creatinine in individuals with varying degrees of renal failure.

Serum oxalate in chronic renal failure.

Serum oxalate is easily controlled in patients with chronic renal failure not yet on dialysis by dietary protein restriction but poorly controlled by both haemodialysis and continuous ambulatory peritoneal dialysis (CAPD). In the control of serum oxalate in chronic renal failure dietary protein restriction is effective in the pre-dialysis patient whereas both CAPD and haemodialysis are relatively inefficient in end-stage renal failure.

Antisecretory effect and oral pharmacokinetics of omeprazole in patients with chronic renal failure.

The inhibitory effect of omeprazole on gastric acid secretion was tested in a group of patients on haemodialysis for chronic renal failure. Single 30 mg doses almost totally inhibited basal acid output on both dialysis and non-dialysis days. Plateau acid output was reduced by a mean of 77% and 90% on non-dialysis and dialysis days respectively. The absorption and pharmacokinetic profile of omeprazole were not affected by dialysis. Omeprazole was not recoverable from dialysis fluid. It is concluded that omeprazole is a potent inhibitor of gastric acid secretion in patients with chronic renal failure, and its effect is not influenced by haemodialysis.

Aluminium toxicity during regular haemodialysis.

In the west of Scotland the incidence of dialysis encephalopathy has been confined to three geographical areas where the concentration of aluminium in the water supply is greatly increased owing to the addition of aluminium sulphate. Eight patients with encephalopathy who dialysed at home in these areas had greatly increased serum aluminium concentrations, and a significant correlation was found between serum aluminium concentrations and the concentrations of aluminium in the water supply. This study provides further evidence that the dialysis encephalopathy syndrome is due to aluminium intoxication, the major source of aluminium being the water supply from which dialysis fluid prepared.

Aluminium studies in dialysis encephalopathy.

The dialysis encephalopathy syndrome has a geographical distribution related to the aluminium content of the dialysis water supply. There is a close relationship between concentrations of water aluminium and serum aluminium, and patients with dialysis encephalopathy have serum aluminium concentrations greater than 400 microgram/litre. High serum aluminium is also associated with osteomalacic bone disease, and worsening anaemia. In dialysis encephalopathy, elevated concentrations of aluminium are found in CSF and in grey matter, and an aluminium burden of 2-8 g is calculated from whole body in vivo analysis. There is sufficient evidence for an aluminium toxicity syndrome to warrant specific removal of aluminium by water purification systems.

Treatment of hypertension with clonidine.

Clonidine, in a daily dosage of 0.15-4.8 mg., effectively lowered systolic and diastolic pressures in 26 out of 28 impatients with moderate to severe hypertension, including five with primary renal disease. The action of the drug did not depend on posture and was not associated with reduction in renal function. Side-effects were not severe, but mental changes occurred in four patients.Clonidine is a useful alternative to currently available antihypertensive drugs, but further evaluation of its longterm efficacy is required.