Albumin dialysis: effective removal of copper in a patient with fulminant Wilson disease and successful bridging to liver transplantation: a new possibility for the elimination of protein-bound toxins.

BACKGROUND: Acute liver failure may be the first manifestation of Wilson disease. If copper elimination fails, liver transplantation is the only remaining therapeutic option. Albumin dialysis, a new method for the removal of protein-bound toxins, was performed in a patient with fulminant Wilson disease. METHODS: An 18-year-old man with Wilson disease presented with hyperacute liver failure, hepatic encephalopathy III, oligo-anuric renal failure, haemolytic anaemia, rhabdomyolysis, pancreatitis and thrombocytopenia. He was treated with albumin dialysis using a 44 g/l albumin-containing dialysate and a slow dialysate flow rate (1-2 l/h). The other details of the technique used are similar to routine continuous veno-venous haemodiafiltration. RESULTS: One hundred and five milligrams of copper were removed by albumin dialysis within the first six treatments, resulting in normalisation of blood-copper levels. Successful treatment of the multiorgan failure was achieved. Hepatic encephalopathy improved within 2 days. The patient initially refused liver transplantation. Therefore 35 additional albumin dialysis treatments were performed. Forty-three grams of bilirubin (an indicator of detoxified substances in the liver) and 196 mg of copper were removed. Multiorgan failure, in particular hepatic encephalopathy, did not recur during 59 days of treatment. Eventually, the patient agreed to liver transplantation and that was successful. CONCLUSION: Albumin dialysis is a new method for the effective treatment of fulminant Wilson disease, resulting in the removal of protein-bound toxins copper and bilirubin. It may serve as a new treatment option in hyperacute liver failure of other origin, acting as an extracorporeal detoxifier.

Significance of antibodies to the recombinant E2 protein of hepatitis G virus in haemodialysis patients.

Patients on maintenance haemodialysis represent a high-risk group for parenterally transmitted viral infections, such as hepatitis B, C and G. In addition to hepatitis G virus (HGV) (GBV-C) RNA, analysed in previous studies, we characterized the seroprevalence rates of antibodies to the putative E2 protein (anti-E2) of HGV in a German cohort of patients on maintenance dialysis (n = 72) in comparison to healthy blood donors (n = 100). The presence of anti-E2 and/or HGV RNA as indicators of present or past HGV infection could be demonstrated in 34.7% of patients and in 16% of the blood donors (P < 0.01). The infection rates with HGV seem to increase only during the first 6 years of haemodialysis. The simultaneous presence of viraemia and anti-E2 was found very rarely in patients and controls. Therefore, the emergence of anti-E2 indicates clearance of HGV viraemia. In conclusion, patients on haemodialysis are at high risk of acquiring HGV infection, but a chronic carrier state with viraemia is rare. The risk of infection is not strictly correlated with the duration of dialysis.

Kinetics of biosynthetic human proinsulin in patients with terminal renal insufficiency.

Eight volunteers with terminal renal insufficiency having consented to the investigation, were given an i.v. bolus administration of 40 pmol biosynthetic human proinsulin on their dialysis-free day. Intravenous blood for the determination of blood glucose proinsulin, insulin and C-peptide was collected in short intervals for 6 hours and thereafter in longer intervals for 24 hours. Proinsulin was determined by immunoradiometric assay with monoclonal antibodies. The proinsulin kinetics were compared with the kinetics of normal volunteers. The behaviour of proinsulin concentration-time is best described with a 3-compartment model. The dominant biological half-life in terminal renal insufficiency was 6.8 hours which signifies a 4.4-fold increase of the normal half-life. The distribution volumes (V1) in the central compartment do not differ in the two groups, whereas the distribution volume after complete distribution (Vss) is significantly increased in renal insufficiency. The total metabolic clearance in renal insufficiency namely 0.63 ml/kg/min is 2.6 times lower compared to normal subjects with 1.67 ml/kg/min. The extra-renal clearance is 39% of the total metabolic clearance rate, whereas the renal clearance comprises 61%. Peripheral conversion from proinsulin to insulin and C-peptide does not occur in terminal renal insufficiency. The basal endogenous proinsulin secretion rate in renal insufficiency does not differ from that of normal volunteers. The following conclusions can be drawn: 1) Hyperinsulinism observed in renal insufficiency can be explained by circulating proinsulin. 2) In the potential therapeutic use of biosynthetic human proinsulin in diabetics with renal insufficiency dosis adjustment according to the remaining renal function would probably be required.

Towards automation of single needle vascular access.

In the past, SN devices have not always fulfilled the expectations of clinicians, but adequate extracorporeal blood flows can only be expected from adequate intravascular flows, which of course applies to any SN method. In some instances, problems may have been caused by poor equipment design, but poor understanding and handling of devices may equally have at fault. Improvement of presently available SN equipment therefore seemed necessary. A fully automatic, second generation cross-over SN control device has been designed which is simple to operate and has the following advantages: Operation is restricted to the speed control setting of the blood pump in the host machine. The CO-SN system automatically responds to changes of fistula flow by modulating the stroke volumes. Recirculation can be kept below 10%. The blood pump rate can be adjusted to the maximum flow rate of the cannulated vessel. Obligatory ultrafiltration is eliminated. Blood compartment pressure is constant. The Munich prototype cross-over SN module was designed as an auxiliary SN equipment which may substitute the Unipuncture machine.

[Unusual therapeutic problems posed by acute kidney failure. Importance of bicarbonate dialysis]. / Les problèmes thérapeutiques particuliers posés par l'insuffisance rénale aiguë. Intérêt de la dialyse au bicarbonate.

The severity of acute renal failure is linked to the associated multiple visceral failures. These failures represent therapeutical challenges that the authors discuss on the basis of their experience of the last 10 years 7 of which being based on the use of bicarbonate dialysis.

[Effects of improved levels of plasma bicarbonates in terminal renal failure]. / Effets de l'amélioration du taux des bicarbonates plasmatiques chez l'insuffisant rénal terminal.

Correction of chronic renal acidosis was attempted for 6 weeks in 20 end stage renal failure patients on chronic acetate hemodialysis by means of 6-9 g of sodium bicarbonate given orally by means of gastric juice resistant capsule of 1 g. Normalisation of the inter-dialysis acid base status was obtained without major side effects.

The conflict between anticoagulation and hemostasis during hemodialysis.

Anticoagulation with comparatively small amounts of heparin has been carried out in more than 3,000 acute and chronic hemodialysis procedures without problems. In a selected high risk group of postoperative and polytrauma patients no patient hemorrhages have occurred, nor have there been any clotting problems in the dialyser circuit. Studies to elucidate the underlying mechanisms of coagulation and anticoagulation in the extracorporeal environment have been performed. Minimal intermittent heparin administration based on plastic anticoagulation monitoring with the APTT method, has proven to be particularly safe.

[Uremic tendencies for hemorrhage and hemodialysis]. / Urämische Blutungsneigung und Hämodialyse.

By means of a simple heparin test which reflects the actual processes in the contact of the blood with heterogeneous surfaces we can securely regulate the heparinisation in each phase of the dialysis, which, as I tried to explain, brings considerable consequences for the clinic.

[Advances in infusion technics]. / Information über industrielle Neuentwicklungen Neuerungen in der Infusionstechnik.

Two interesting developments in the area of infusion technology are being presented. The first product concerns a rather simple, but precise, and manually ajustable flow control device for intra-venous fluid administration without the need of having an infusion pump. The second product concerns a continuous flush device for arterial and venous indwelling cannulae. The main area of clinical application of the latter product is the combination with intraarterial catheters which are used to monitor various arterial pressures. Adaptation of the device to intravenous catheters is also possible. The main benefit derived from the flushing device is a significant prolongation of catheter function and patency.

Artificial organ support strategies in combined renal, circulatory, pulmonary and liver failure.

Within recent years we have significantly broadened the indication for the treatment of acute renal failure in intensive care patients, even in the presence of multiple organ failure. This was made possible by: 1. safe heparinization of the extracorporeal circulation while avoiding bleeding tendencies 2. hemofiltration of patients threatened by pulmonary complications early during renal failure and 3. the simultaneous use of various special intensive care measures. By this approach we have succeeded in a number of cases to break the chain of complications leading to multiple organ failure and death.

[Heparin dosage in chronic hemodialysis (author's transl)]. / Die heparinisierung des chronischen Dialysepatienten.

Over a period of 10 months hemodialyses in 20 patients with chronic renal failure were performed with a 40% lower heparin-dose. Blood coagulation was controlled from the activated partial thromboplastin time (APTT). There were no unfavourable side-effects, also the effectivity of the hemodialyses was not changed. However, we measured a significant increase in the hemoglobin-concentration and in the packed cell volume. Bleeding from the punctures was significantly shortened.

[Angiographic findings due to malfunction of Cimino shunts in haemodialysis patients (author's transl)]. / Angiographische Befunde bei Störungen des CIMINO-Shuntes von Hämodialysepatienten.

Both the arterial and venous limb of a Cimino shunt can be well demonstrated by injection of contrast medium into the shunt vein during transient arterial and venous ccompression with a blood pressure cuff. Twenty-four angiograms in patients with shunt malfunctions carried out in this way were analysed with respect to various vascular changes.

[Control of the heparin induced bleeding risk in haemodialysis patients (author's transl)]. / Vermeidung des heparinbedingten Blutungsrisikos bei der Hämodialyse

Partial-Thromboplastin-Time (PTT) has been used as a bedside-method to control the dosage of heparin in haemodialysis patients at a high bleeding risk. The practical procedures and the advantages of the method as compared to current coagulation controls are outlined. As a result a technique of "minimal intermittent heparinization" has been developed which effectively prevents bleeding in the heparinized patient on haemodialysis.