Bernhard Kreymann

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.

Citrate pharmacokinetics and calcium levels during high-flux dialysis with regional citrate anticoagulation

Background. Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of hypocalcaemia. We studied citrate and calcium kinetics to better understand safety aspects of this anticoagulation method. Methods. During 15 haemodialysis treatments with a calcium-free dialysis solution, citrate was infused pre-dialyser and calcium was substituted post-dialyser. Systemic and extracorporeal citrate and calcium concentrations were repeatedly measured to calculate citrate and calcium pharmacokinetics. Results. Removal by dialysis constituted the major elimination pathway of citrate (83 ± 5%). Systemic citrate load and concentrations were low (17 ± 7 mmol/4 h, 0.3 ± 0.15 mmol/l). Combined use of calcium-free dialysate and citrate infusion increased diffusible calcium to 80% of total calcium and induced substantial dialytic loss of calcium (43 ± 4 mmol/4 h). Since calcium was substituted, systemic calcium balances were positive (∼+5 mmol) and concentrations stable. Calcium supplementation correlated with calcium dialytic losses, which in turn were dependent on total calcium and haematocrit. Conclusions. When using calcium-free dialysate during citrate anticoagulation, hypocalcaemia is very likely unless calcium is re-infused, because large amounts of calcium are lost in the dialysate. However, an accumulation of citrate in the patients systemic circulation is an unlikely cause of hypocalcaemia since most of the citrate is removed by dialysis. Calcium substitution and monitoring are the most important safety measures. We propose a rational approach based on haematocrit and total calcium for the choice of the starting calcium supplementation rate.

Haemodialysis for the prevention of contrast-induced nephropathy: outcome of 31 patients with severely impaired renal function, comparison with patients at similar risk and review.

Huber W, Jeschke B, Kreymann B, et al. Haemodialysis for the prevention of contrast-induced nephropathy. Outcome of 31 patients with severely impaired renal function, comparison with patients at similar risk and review. Invest Radiol 2002;37:471–481. Rationale and Objectives.To investigate whether haemodialysis prevents contrast-induced nephropathy (definition: increase of serum-creatinine of ≥ 0.5 mg/dL within 7 days). Materials and Methods.Thirty-one patients (mean serum-creatinine 4.01 ± 1.83 mg/dL) were dialyzed for 4.36 ± 1.0 hours within one hour after 278.4 ± 160.5 mL of contrast medium. Results.Dialysis resulted in a significant reduction of serum-creatinine (2.25 ± 1.46 mg/dL;P < 0.0001) and stable mean serum-creatinine levels 2, 3, 4, and 7 days after contrast medium and at discharge compared with baseline values. However, 19 patients (61%) developed contrast-induced nephropathy within 7 days. Four patients had to be repeatedly dialyzed. A comparison of our patients’ 48 hours-incidence of contrast-induced nephropathy (9/31; 29%) versus patients at comparable risk included in seven previous studies demonstrated a prophylactic effect of dialysis only versus a subgroup in one study. Conclusions.Data provide no hint that haemodialysis prevents contrast-induced nephropathy. Therefore, postprocedural dialysis should be restricted to patients participating in clinical studies.

Multi-modal treatment of calciphylaxis with sodium-thiosulfate, cinacalcet and sevelamer including long-term data.

Background: Calciphylaxis is a rare, yet life-threatening disease mainly occurring in dialysis patients. Traditional options of treatment remain unsatisfactory. Methods: Here we present a novel, combined approach, treating calciphylaxis with IV sodium thiosulfate, cinacalcet and sevelamer. In a case series five hemodialysis patients, have been successfully treated with this regimen. Treatment and survival data were analyzed using descriptive statistics. Results: In all patients, a rapid decrease in pain, improvement of general condition and wound healing within six months occurred. Side effects were low. Drug dosages: IV sodium thiosulfate initial dose 119.4 +/- 84.9 g/m2/week, maintenance dose 40.6 +/- 9 g/m2/week; cinacalcet: maintenance dose 36 +/- 32.9 mg/d and sevelamer maintenance dose 3320 +/-1671 mg/d. One and two year survivals were 100 % and 80 %, respectively. We also report on long-term application of IV sodium thiosulfate of up to 52 months. Patient survival after diagnosis was 52, 84, 21, 36 and 30 months, respectively. Survival since initiation of hemodialysis was 76, 136, 89, 36 and 35 months, respectively. Conclusion: This novel combined approach, a multi-modal treatment of calciphylaxis with persistent hyperparathyroidism, using IV sodium thiosulfate, cinacalcet and sevelamer seems to improve the outcome of this devastating disease.

Evaluation of the Hepa Wash®treatment in pigs with acute liver failure

BackgroundMortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF.MethodsIn the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h.ResultsAll animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed.ConclusionsHepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Sclerosing encapsulating peritonitis: MRI diagnosis

Sir, A 53-year-old man started continuous ambulatory peritoneal dialysis 9 years before renal transplantation due to end-stage renal failure. He then received a cadaveric kidney graft under an immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil and methylprednisolone. Two years after transplantation, the patient developed bowel dysfunction with associated abdominal pain, constipation, vomiting, and rapid loss of weight (8 kg within 6 months). The patient was admitted to our hospital. Physical examination and laboratory tests were inconspicuous, serum creatinine and BUN were within normal range and the graft function was excellent. Upper GI series (Fig. 1b) and MRI using a heavily T2-weighted HASTE sequence after oral administration of water (Fig. 1a) showed dilatation of a proximal jejunal loop. In addition, MRI demonstrated circumscribed focal wall thickening. According to the history and the radiographic findings, sclerosing encapsulating peritonitis (SEP) was suspected. Excision of a short, obstructivesegment of the small bowel secondary to dense fibrosing of the connective tissue was performed. The N. Hüser . M. Stangl Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany

A Model of Ischemic Isolated Acute Liver Failure in Pigs: Standardizing Monitoring and Treatment

Background: Acute liver failure (ALF) models in pigs have been widely used for evaluating newly developed liver support systems. But hardly any guidelines are available for the surgical methods and the clinical management. Methods: The study validated several standard operating procedures describing in detail the surgical method and intensive care monitoring and treatment (control of potassium, glucose and bicarbonate levels, cardiovascular and intracranial pressure monitoring, etc.). ALF was induced in animals with a mean of 56 kg. Two surgical methods were compared: ligation of hepatic arteries with either end-to-side portacaval shunt (ESPS) and bile duct ligation or side-to-side portacaval shunt (SSPS) without bile duct ligation. Results: During total portal vein clamping, the animals in the ESPS group developed severe hypotension, splanchnic congestion and metabolic acidosis. One animal died after approximately 1.5 h. This model therefore represents a multiorgan failure model rather than an isolated ALF model. In the SSPS group, none of these side effects were observed, while clinical, laboratory and histopathological signs of ALF were evident. Conclusions: A reproducible model in pigs representing ALF can be established with the help of the standardized monitoring and treatment procedures presented.

Grundlagen der Nieren- und Leberdialyse

Die Dialyse ist ein kunstliches Blutreinigungsverfahren, das sowohl mit der Nachahmung physiologischer Vorgange als auch mit der Benutzung bestimmter physikalisch- chemischer Gesetze arbeitet. Ihre technische Umsetzung in einer Dialysemaschine sowie chirurgische und internistische Interventionen gehoren zu dem Zusammenspiel unterschiedlicher Disziplinen, die eine Dialyse ermoglichen. Die Grundlagen des Dialyseverfahrens, die Maschine und die Unterschiede von Nieren- und Leberdialyse sollen im Folgenden erklart werden. Heute besteht in der Bundesrepublik Deutschland bei ca. 55.000 Patienten ein chronisch dialysepflichtiges Nierenversagen (Stand 2005). Das Leben dieser Patienten kann mit der Dialyse um Jahrzehnte verlangert werden. Damit ist die Nierendialyse eines der erfolgreichsten medizintechnischen Verfahren. Bei der Leberdialyse sind ebenburtige Erfolge noch nicht erzielt worden. Umso wichtiger ist es, hier neue Wege zu finden, um auch fur Leberpatienten ein effizientes Dialyseverfahren zu etablieren.

Vom 1-Mann-Start-up zum voll QM-zertifizierten Medizintechnikunternehmen

Unternehmensgrundungen sind stets mit ausergewohnlichen Belastungen fur den Grunder verbunden, doch Start-ups im Medizintechnikbereich mussen sich noch zusatzlichen Herausforderungen stellen. Aufgrund des hohen Entwicklungsaufwands sind sie sehr kapitalintensiv und nicht fur alle Phasen der Grundung gibt es ausreichend Geldgeber. Gleichzeitig bestimmen in diesem Sektor nicht Angebot und Nachfrage die Preise von Produkten und Dienstleistungen, stattdessen legen staatliche Organisationen die Erstattungsfahigkeit und die Erstattungsbetrage fest – ein erheblicher Unsicherheitsfaktor. Bei der Produkteinfuhrung in den Krankenhausern mussen unterschiedlichste Stakeholder uberzeugt werden, was ein hohes Mas an Fingerspitzengefuhl erfordert. Dieser Beitrag erlautert, wie der Hepa Wash GmbH trotz zahlreicher erwartbarer aber auch uberraschender Widrigkeiten die Markteinfuhrung des weltweit ersten Verfahrens zur erweiterten und individualisierten Unterstutzung der Hauptentgiftungsorgane Leber, Lunge und Niere gelungen ist.