Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.

BACKGROUND: There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane. METHODS: 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate). FINDINGS: At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension). INTERPRETATION: There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

Combination chemotherapy with CHOP for recurrent thrombotic thrombocytopenic purpura.

We report the case of a 42-year-old woman with chronic recurrent thrombotic thrombocytopenic purpura. Therapy with corticosteroids, high-dose immunoglobulins, plasma exchange and cyclophosphamide only induced short-lasting remissions during a course of almost 3 months. Following a severe relapse on day 90 after the start of symptoms, polychemotherapy with cyclophosphamide. adriamycin, vincristine and prednisolone (CHOP) was begun. After two cycles of CHOP the patient has stayed in complete remission, with normal platelet counts for more than 9 months to date.

Advantages of isovolemic large-volume erythrocytapheresis as a rapidly effective and long-lasting treatment modality for red blood cell depletion in patients with polycythemia vera.

Long-term survival of patients with polycythemia vera (PV) is essentially determined by the ability to reduce the risk of thromboembolic complications resulting from the altered rheological conditions by the high red blood cell (RBC) mass of these patients. RBC depletion to normal hematocrit (Hct) values is the first line therapy and should be preferred to chemotherapy (or P32) because of the long-term risk of acute leukemia or other secondary malignancies. RBC depletion is accomplished much more effectively and rapidly by erythrocytapheresis (EA) than by repeated phlebotomies and has been shown to be well tolerated and accepted by the patients (8). The main indications for EA for a PV patient (often newly diagnosed) are high risk Hct values of >55-60% that can be reduced to the normal range within 1-2 h. The long-lasting effect (median interval between 2 EA treatments: ca. 6 months) is partially the result of the massive loss of iron, a growth factor for erythropoesis. This has been shown by in vitro studies in erythroid progenitor cells of PV patients before and after EA (11). The advantages and possible disadvantages of EA treatment are discussed.

Specificity of circulating and tissue-bound autoantibodies in Goodpasture syndrome.

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.

[Change in renin activity and blood pressure in the dog autologous kidney transplant model with modified HTK solution]. / Veränderung der Reninaktivität und des Blutdruckverhaltens im autologen Nierentransplantationsmodell am Hund bei Modifikation der HTK-Lösung.

Investigations of changes in activity of renin and blood pressure after reperfusion of the kidney transplant using HTK solution were carried out by means of an autologous, heterotopic model of kidney transplantation applied to dogs. Duration of cold ischemia was 48 h. According to variations in the composition of the HTK perfusion solution three test groups were set up. During the first 20 min after recirculation in each test group the renal venous and arterial renin activities were measured. Parallel to renin activity, the arterial blood pressure was recorded. During the first few minutes following recirculation of the kidney transplant the renin levels in the venous blood of the kidney were higher in test group 1 (HTK solution, perfusion height 120 cm) than in either of the other two, showing a median maximal increase of 195 ng/ml.h. In test group 2 the maximal venous renin concentration fell to 145 ng/ml.h, while graphs take a more uniform course. Test group 3 (HTK/tryptophan) differed from the others in having further improved renin values. After the 7.5 min of observation normal venous renin concentrations were measured following earlier values for maximal increase between 23.1 ng/ml.h and 120 ng/ml.h (median 61.5 ng/ml.h). The best reperfusion of the kidney was observed in the tryptophan group, albeit without any recognizable positive effects on the other renal functions. Initially low renin values do not necessarily correlate with a smooth postoperative renal function and vice versa. Initial renin values cannot provide a secure basis for predicting instant as well as long-term postoperative functions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemolytic-uremic syndrome in pneumococcal meningitis and infection. Importance of T-transformation]. / Hämolytisch-urämisches Syndrom bei Pneumokokken-meningitis und -sepsis. Bedeutung der T-Transformation.

A 4 month old girl developed a severe hemolytic uremic syndrome (HUS) following pneumococcal sepsis and meningitis. As a result of the hemolytic anemia and thrombocytopenia with associated gastrointestinal bleeding several red blood cell and thrombocyte transfusions became necessary. No plasma was transfused to the patient and all cellular blood components to be transfused were washed thoroughly in order to avoid the administration of eventually dangerous donor anti-T antibodies. Continuous peritoneal dialysis was performed for 23 days until sufficient spontaneous urine production was resumed. From the start of increased hemolysis T-transformation of the patient's red blood cells could be shown; bacterial neuraminidase was proven in the patient's serum, which could be neutralized in vitro by a commercial intravenous IgG preparation. The direct Coombs-Test was negative and no significant amounts of anti-T antibodies were detectable in the patient's serum at any stage of the disease. Our observation suggest that the T-transformation itself has caused the increased hemolysis and not an antigen-antibody (T-anti-T) reaction. In cases of HUS und proven T-transformation, intravenous IgG preparations should be tried therapeutically to inhibit the bacterial neuraminidase.

[Rhinocerebral mucormycosis during deferoxamine therapy]. / Rhinozerebrale Mucor-Mykose unter Deferoxamin-Therapie.

A 24-year-old woman had been in full remission of an acute myeloid leukaemia since 1988, but she required regular erythrocyte and platelet transfusions for pancytopenia. To counteract a progressive siderophilia due to the transfusions (ferritin levels of about 10,000 ng/ml) deferoxamine was intermittently given intravenously (5 g after each transfusion). Seven months after the start of this treatment the patient was hospitalized because of severe left-sided facial pain as well as reddening and swelling in the periorbital region. As maxillary and frontal sinusitis was suspected, antibiotics were administered (at first three times daily 2.2 g amoxicillin and clavulanic acid, then two times daily 300 mg rifampicin and 200 mg ciprofloxacin). Nonetheless, orbital phlegmon developed within a few days with protrusion and blindness of the left eye necessitating a decompression operation. Material obtained at operation revealed rhinocerebral mucormycosis. After 3 weeks of antimycotic treatment with both amphotericin B (1 mg/kg.d) and flucytosine (150 mg/kg.d) the mucormycosis healed without the necessity of extensive and disfiguring removal of necrotic tissue. But the blindness in the left eye, caused by occlusion of the central artery, was irreversible.

Characterization and quantification of anti-T in human serum using a reliable hemolysis test.

The need of fresh-frozen donor plasma with a low level of anti-T has been emphasized recently. Anti-T, as administered by transfusion of fresh-frozen plasma, has been accused repeatedly of enhancing hemolysis in septic children with T transformation of red cells. Therefore, a new hemolysis test for the quantification of anti-T in human serum has been developed. With our test, anti-T-poor plasma donors can be found. Additional results raise substantial doubt as to the pathogenetic role of anti-T in the development of the hemolytic-uremic syndrome, found in septic children with red-cell T transformation. It is impossible to predict in vivo hemolysis induced by anti-T knowing the temperature characteristics and the ionic conditions causing this antibody to mediate hemolysis in vitro. Obviously, T transformation itself plays the major pathogenetic role in these patients, and not the presence of anti-T. In the case of disseminated intravascular coagulation, a content of anti-T cannot be construed as prohibiting transfusion of fresh-frozen plasma to such patients.

Complications of plasma exchange in patients with neurological diseases.

Plasma exchange has proven to be effective in diseases of established or presumed autoimmune etiology as well as in hyperviscosity syndromes and some rare metabolic disorders. Its application is thought to be relatively safe; nevertheless, severe complications may occur. We therefore analyzed the complications of 291 exchanges in 39 patients with neurological diseases. Minor complications developed in 4.8% and major complications in 2.7% of procedures, including one death. Severe infections and technical problems have been the most serious side effects, sometimes followed by organ failure or even death.

[Hemolytic-uremic syndrome in an adult with T-cryptantigen liberation]. / Hämolytisch-urämisches Syndrom des Erwachsenen mit T-Kryptantigen-Freilegung.

Haemolytic uraemic syndrome was diagnosed in a 36-year-old woman with acute renal failure (creatinine 10.5 mg/dl), haemolytic anaemia (haemoglobin 9.7 g/dl, lactate dehydrogenase 1926 U/l) and thrombopenia (98,000/microliters). After initial plasmaphereses and high doses of furosemide all symptoms disappeared within three weeks. The lectin tests demonstrated that the illness was connected with the liberation of T-crypt-antigen (Thomsen-Friedenreich antigen) on the erythrocytes. This special form of the haemolytic uraemic syndrome (neuraminidase-induced haemolytic uraemic syndrome) has previously been observed almost exclusively in children. However, for diagnosis and differentiation of haemolytic uraemic syndromes the presence of liberated T-antigen on erythrocytes should also be tested for in adults.

Treatment of polycythemia vera by isovolemic large-volume erythrocytapheresis.

Excess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension - as measured in 8 patients - increased. Hct was reduced by EA from 56.8% +/- 5.6% to 41.9% +/- 6.6%, Hb from 17.5 +/- 2.3 to 12.7 +/- 2.4 g%, RBC counts from 7.4 +/- 0.9 to 5.4 +/- 0.9 x 10(6)/mm3. The mean volume of the apherisate was 1410 +/- 418 ml, (mean Hct 79.7% +/- 9.3%), and the actual RBC volume removed 1113 +/- 367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58% +/- 5.7% and 41.5% +/- 4.9%) were regularly followed after EA the mean period with Hct less than 50% after a single EA procedure was 6.1 +/- 4.1 months (median, 6); in 14 out of these 21 patients a Hct of less than 43% after EA was reached and their mean period with Hct less than 50% after EA was 7.6 +/- 4.0 months (median, 7.5). For three patients this period was 11, 13, and 15 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)