Baclofenintoxikation bei chronischer Hämodialyse und Nierentransplantation

Fourteen days after renal transplantation, at first gave with good transplant function, a 36-year-old woman developed neurogenic dysfunction of bladder emptying. This was treated with baclofen, 5 mg three times daily by mouth. Between the 7th and 10th treatment day she progressively developed an organic psychotic syndrome and increasing respiratory paralysis after the onset of renal failure, associated with rejection of the transplanted kidney which required dialysis. Plasma concentration of baclofen was 565 ng/ml (therapeutic range 80-400 ng/ml). After discontinuing the drug and renewed haemodialysis the baclofen level rapidly fell and the symptoms receded. In a second case, a 57-year-old …

IgG Subclass Distribution of Autoantibodies to Glomerular Basement Membrane in Goodpasture’s Syndrome Compared to Other Autoantibodies

The IgG subclass distribution of autoantibodies to glomerular basement membrane (anti-GBM antibodies) was investigated and compared to the distribution of liver-kidney microsomal (LKM) autoantibodies in chronic active hepatitis, to antimitochondrial autoantibodies (AMA) in primary biliary cirrhosis, and to the subclass distribution of total serum IgG within a healthy population. Solid phase assays for the demonstration of these autoantibodies were performed with four mouse monoclonal antibodies specific for each human subclass to provide quantitative data for the autoantibodies. In addition, the subclass distribution of total IgG in these sera was analyzed. IgG1 accounted for 75% of the tot…

Funktionelle Beziehung zwischen Leber und Niere: Teil II. Wasserexkretion und hepatorenales Syndrom*

Acanthocyturia—A characteristic marker for glomerular bleeding

Acanthocyturia—A characteristic marker for glomerular bleeding. Erythrocyte morphology by phase contrast microscopic examination (PCM) of the urine is widely employed in distinguishing glomerular from nonglomerular bleeding. The proposed percentages of dysmorphic red cells are significant for glomerular bleeding in the range of 10 to 80% in the literature, because there is no clear cut definition of “dysmor-phism.” In the present study midstream urine samples of 351 patients with hematuria (> 8 erythrocytes/μl) and of 33 healthy controls were examined. The various dysmorphic red cells were analyzed by PCM according to a detailed hematological classification. Most of the dysmorphic red cells…

Glomerulonephritis und Hepatitis-B-Virus-Infektion

Funktionelle Beziehung zwischen Leber und Niere: Teil I. Natriumexkretion*

Immundefekt bei Niereninsuffizienz: Teil II. Mechanismen des »urämischen« Immundefekts*

Accumulation and Adverse Effects of Metoprolol and Propranolol After Concurrent Administration of Cimetidine

Pharmacokinetics of metoprolol, propranolol and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (p < 0.05). The AUC of the two last mentioned beta blockers behaved similarly (p < 0.05). Measurement of exercise-induced tachycardia on the 6th day of administration showed no differences between monotherapy with the bet…

Influence of Thymopentin on Antibody Response, and Monocyte and T Cell Function in Hemodialysis Patients Who Fail to Respond to Hepatitis B Vaccination

We investigated the influence of thymopentin as an adjuvant for hepatitis B vaccination on in vitro monocyte and T cell function and in vivo antibody response in a prospective, placebo-controlled double-blind trial in 20 low- and nonresponders to hepatitis B vaccination on chronic hemodialysis. 50 mg thymopentin was given subcutaneously twice per week for 3 weeks, followed by 1 intramuscular injection of 40 micrograms HB-Vax and 3 subsequent injections of thymopentin. After 1 month, the patients were boostered with 40 micrograms HB-Vax. There was no significant difference in T cell and monocyte function after administration of thymopentin, as determined in vitro. After 3 months, 3 patients …

Multiple osteoartikuläre Komplikationen (dialyse-assoziierte Spondarthropathie) und Karpaltunnelsyndrom bei chronischer Hämodialyse

Abstract During a nine-year treatment by haemodialysis for renal failure a now 57-year-old woman developed multiple complications of the skeletal system. Acute calcific periarthritis of the right shoulder became manifest one year after the start of the haemodialysis, followed the next years by progressive arthropathy with subchondral amyloid cysts of both shoulders, effusions in the knee-joint and destructive spondylarthropathy of the middle vertebrae. Carpal-tunnel syndrome also occurred, caused by a beta 2-microglobulin amyloidosis (beta 2-microglobulin concentration in serum 42.6 ng/l) and an aluminium osteopathy. These multiple complications, observed here in one patient, are each of th…

Pharmacokinetics of atenolol in relation to renal function

The plasma levels and urinary excretion of carteolol and its main metabolites 8-hydroxycarteolol and carteolol glucuronide were investigated in 6 healthy subjects and 9 patients with varying degrees of renal impairment following a single oral dose of 30 mg carteolol hydrochloride. In healthy subjects the half-life of carteolol was 7.1 h. 63% of the administered dose was recovered unchanged in urine, and in all 84% was excreted by the kidneys. The renal clearance of carteolol was 255 ml/min. In chronic renal failure (CRF) the terminal half-life was increased to a maximum of 41 h. Both the elimination rate constant and renal clearance were closely related to the creatinine clearance. In CRF t…

Alkohol und IgA in der Niere

Bei Patienten mit chronischer alkoholischer Lebererkrankung kommt es zum Anstieg von Immunglobulin A im Serum mit uberproportionaler Zunahme der polymeren Form sowie zum Auftreten von IgA-haltigen Immunkomplexen. Die Ursachen liegen einerseits in einer alkoholinduzierten intestinalen Permeabilitatssteigerung fur Makromolekule mit Stimulierung der lokalen IgA-Immunabwehr, andererseits in einer verminderten hepatischen Clearance von polymerem IgA. Fur die Storung der hepatischen Elimination durfte ein hepatozellularer, von der sekretorischen Komponente unabhangiger Mechanismus verantwortlich sein. Bei annahernd der Halfte der Patienten mit alkoholischer Leberzirrhose findet sich in den Glomer…

Hepatitis-B-Impfung bei Dialysepatienten*

Sekundärer Immundefekt bei Niereninsuffizienz am Beispiel der Hepatitis B-Impfung

In dialysis patients the immune response to hepatitis B-vaccination is greatly impaired. In vitro the non-responders show a failure of the monocytes to support the process of primary T-cell activation. This defect results in a lack of interleukin 2-production and an enhanced sensitivity of the interleukin-2 receptor system. Addition of low doses of interleukin-2 fully reconstitutes the deficient immune response in vitro. Furthermore, the local application of low dose interleukin-2 during a standard vaccination with 40 µg hepatitis B-vaccine normalizes the non-responder state in vivo.

Acanthocyturia detects glomerular bleeding.

Rare association of herpes simplex virus IgM-specific antibodies and Guillain-Barré syndrome successfully treated with plasma exchange and immunosuppression

Herpes simplex virus (HSV) has been associated with various neurological disorders. In contrast, HSV infection is very rarely found in acute polyneuroradiculitis. In this report, a patient is described with a severe course of Guillain-Barr¿ syndrome (GBS). HSV IgM-specific antibodies and a rise of complement-fixation antibodies were detected. During the acute phase of neurologic syndrome, a nerve biopsy showed myelin damage and IgM deposits on the inner layer of the perineurium. Plasma exchange, in combination with immunosuppression, was successfully applied as a treatment in the relapsing course of GBS. Finally, after recovery, HSV-specific IgM antibodies disappeared.

Angiomyolipome der Nieren bei Morbus Bourneville-Pringle

Three cases with renal angiomyolipoma in Bourneville's disease are reported. In two patients advanced renal insufficiency developed, one being treated by chronic intermittent hemodialysis. In the third patient rupture of angiomyolipoma with severe retroperitoneal bleeding occurred. In one patient, tumorous enlargement initially was diagnosed only in the right kidney and preceded angiomyolipoma of the left kidney for several years. In this patient nephrectomy was performed because malignancy was assumed before diagnosis of Bourneville's disease was established. Occasionally, histology may suggest sarcomatous changes. However, the absence of distant metastasis and the overall long survival of…

Interaction of atenolol with furosemide and calcium and aluminum salts

Six healthy subjects were treated with 100 mg atenolol. After a therapy-free interval of 4 wk the same subjects received the same dose of atenolol with furosemide, 40 mg, with calcium (as the lactate gluconate and carbonate), 500 mg, or with aluminum hydroxide, 5.6 gm. Atenolol alone and in combination was administered first as a single oral dose; a long-term 6-day treatment began 48 hr later. Addition of furosemide did not influence atenolol kinetics, but aluminum hydroxide led to an insignificant reduction (P greater than 0.05) of mean peak plasma levels of about 20% and of the area under the plasma concentration-time curve (AUC -infinity) from 5818 to 4353 ng ml-1 hr (P greater than 0.05…

Impaired cellular immune responses in chronic renal failure: Evidence for a T cell defect

Impaired cellular immune responses in chronic renal failure: Evidence for a T cell defect. Cellular immune responses in vitro were studied in 24 patients on chronic hemodialysis and 16 healthy volunteers with normal kidney function. Patients on maintenance hemodialysis had lymphopenia with diminished numbers of both T4 + and T8 + T-lymphocytes. The T4/T8 ratios were within the normal range. Peripheral blood lymphocytes (PBL) showed a diminished proliferative response upon stimulation with concanavalin A, phytohemagglutinin and poke weed mitogen. When cell surface antigens were used for stimulation (mixed lymphocyte culture) uremic lymphocytes also showed a lower proliferation rate. Although…

Minimalheparinisierung bei Dialysepatienten mit erhöhter Blutungsgefährdung

Abstract In 78 patients (47 men, 31 women; mean age 53 [22-78] years) 174 dialyses were undertaken within one week of a bleeding episode or a diagnostic or therapeutic procedure which may cause bleeding. Minimal anticoagulation with low molecular weight heparin (LMWH) was the aim, using a biocompatible dialyser. During the dialysis coagulation was controlled by global tests (Quick value/international normalized ratio [INR], partial thromboplastin time, thrombin time, antifactor Xa activity), by molecular markers of clotting activity (thrombin-antithrombin III complex [TAT], D-dimers), as well as measurement of elastase (elastase-alpha 1-protein inhibitor complex). The LMWH dosage averaged 9…

LOW-DOSE INTERLEUKIN-2 INDUCES SYSTEMIC IMMUNE RESPONSES AGAINST HBsAg IN IMMUNODEFICIENT NON-RESPONDERS TO HEPATITIS B VACCINATION

Abstract A metabolic monocyte defect appears to correlate with non-responsiveness to hepatitis B vaccine in many patients on haemodialysis. This defect prevents production of interleukin-2 during T-cell activation after antigen contact. Receptors for interleukin-2 are, however, expressed in greater numbers than in healthy subjects or uraemic responders to hepatitis B vaccination. In this study, ten uraemic patients, previous non-responders to vaccination against hepatitis B, were revaccinated with the same vaccine combined with one intramuscular injection (2·5 × 10 5 U) of natural human interleukin-2. Systemic production of antibodies against hepatitis B surface antigen was initiated in tho…

Immunbiologie der Transplantatabstoßung und deren pharmakologische Beeinflussung

Dot-immunobinding assay with the globular domain of collagen type IV for antiglomerular basement membrane antibodies

A dot-immunobinding assay for the detection of antiglomerular basement membrane antibodies has been developed. The globular domain NC1 of basement membrane collagen type IV was used as antigen. The assay proved to be specific, sensitive, and reproducible. Circulating antibodies in each of 12 sera from patients with florid Goodpasture's syndrome could be demonstrated, whereas sera from patients with Goodpasture's syndrome in clinical remission and various control sera showed no reactivity. The advantages of the dot-blot assay are: the usage of the purified Goodpasature target antigen NCI reduces unspecific binding of IgG; only minimal amounts of antigen are required to give a positive signal…

Atenolol interaction with aspirin, allopurinol, and ampicillin.

Atenolol kinetics were investigated in six healthy subjects after 100 mg orally, as monotherapy a 6-day treatment began 48 hr later. After a therapy-free interval of 4 wk, the same subjects received the same dose of atenolol with 1 gm ampicillin, 500 mg aspirin, and with 300 mg allopurinol. Allopurinol and aspirin did not substantially alter the kinetics of atenolol. After a single oral dose of 100 mg atenolol combined with 1 gm ampicillin, the bioavailability of atenolol was reduced to 36 +/- 5% compared to 60 +/- 8% after monotherapy. During long-term treatment with atenolol and ampicillin the bioavailability of atenolol fell to 24% (P less than 0.01). Mean peak plasma levels were lowered…

Uremic serum inhibits monocyte-dependent, but not interleukin-2-dependent steps of T cell proliferation.

We examined the influence of uremic serum on antigen receptor triggered T cell proliferation in dialysis patients with impaired immune function, i.e., 12 nonresponders to hepatitis B vaccination. The dialysis patients showed a monocyte dysfunction and an increased responsiveness to interleukin 2 (IL-2) according to our previous findings. In vitro the addition of IL-2 completely reconstituted the defect. Uremic serum inhibited monocyte-dependent T cell proliferation of patients and of healthy controls. Contrary, monocyte-independent steps of T cell proliferation were not impaired by uremic serum. When IL-2 was added to cultures, the T cell proliferation in the presence of uremic serum was ev…

Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression o…

Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure: results of the ANNE study

It was found that in Belgium, renal imaging techniques, demonstrating a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications, were the only methods to reliably diagnose analgesic nephropathy (AN) in patients with end-stage renal failure. However, these criteria were selected in an area with a high prevalence of this disease (15.6% of the dialysis population at December 1990). To evaluate the criteria selected to diagnose AN in populations with lower or unknown prevalences of AN, the Analgesic Nephropathy Network of Europe (ANNE) was formed, consisting of 23 dialysis units from 14 European countries and Brazil. During 1991-1992, 598 new patient…

Active hepatitis B vaccination of dialysis patients and medical staff

AbstractActive hepatitis B vaccination of dialysis patients and medical staff. One hundred six patients with terminal renal insufficiency and 29 medical personnel were given three doses of hepatitis B vaccine at an interval of 0, 1, and 6 months (Merck, Sharp and Dohme, West Point, Pennsylvania, part of a joint study no. 649). Chronic hemodialysis patients (N = 99) received 40 µg vaccine (V) i.m. Uremic patients, who were just about to start chronic dialysis treatment (N = 7), were given 40 µg V, and at the first vaccination 3ml hyperimmune globulin (HBIG) in addition. The medical personnel was alternately vaccinated with 20 µg V (N = 8), 40 µg (N = 11), 40 µg V, and 3ml HBIG at the first v…

Assoziation einer arteriellen Verschlußkrankheit mit Ciclosporin-Therapie nach Nierentransplantation

Renal transplantation followed by immunosuppression with cyclosporine (whole-blood levels 200-300 micrograms/l) and methylprednisolone (4 mg daily) was performed in a 54-year-old man with chronic glomerulonephritis. Three years later rapidly progressive arterial obstructive disease (peripheral type) developed. Parenteral treatment with prostaglandins, calcium antagonists and nitrates, as well as a lumbar sympathectomy, was unsuccessful so that, in rapid succession, several amputations on upper and lower limbs became necessary. The disease progression was arrested only when azathioprine replaced cyclosporine. Raynaud's phenomenon, present at the time, also disappeared and analgesics were no …

T cell activation defect in hemodialysis patients: Evidence for a role of the B7/CD28 pathway

T cell activation defect in hemodialysis patients: Evidence for a role of the B7/CD28 pathway. The immunosuppressive effect of chronic renal failure is correlated with an impaired proliferation of peripheral blood leukocytes in vitro . This is mainly due to an impaired function of the accessory cells rather than the T cells. Here we tried to define a missing accessory signal for T cell activation in hemodialysis patients. We substituted cell surface bound molecules by adding tumor cell lines to the in vitro assays that express different patterns of accessory molecules. Cell lines that express the costimulatory B7 molecule reconstituted the activation of patients' cells whereas B7 negative c…

Autosomal dominant polycystic kidney disease—in vitro culture of cyst-lining epithelial cells

The major form of autosomal dominant polycystic kidney disease (ADPKD) in humans is linked to the PKD1 gene on chromosome 16p. The identity of the gene and the underlying pathogenetic mechanisms are not yet defined. Cyst-lining epithelial cells derived from a polycystic kidney were successfully grown in culture and designated MZ-PKD-1 cells. By linkage analysis, the related pedigree of the nephrectomized patient could be linked to the PKD1 gene on chromosome 16p. Thus, these cells exhibit the genotype of a mutated PKD1 gene and represent an in vitro culture model for ADPKD involving chromosome 16p. The antigenic phenotype was characterized immunohistologically by epithelial differentiation …

Immundefekt bei Niereninsuffizienz: Teil I. Klinische Manifestationen*

Antiglomerular basement membrane antibodies in human sera: Detection by a modified micro-ELISA

An enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to human glomerular basement membrane has been developed. Special emphasis has been put on the choice of microtiter plates which were coated with a collagenase digest of human glomerular basement membrane. Results differed markedly between the different microtiter plates. Best results were obtained with a flexible polyvinylchloride microtiter plate with flat wells (Dynatec). This plate exhibited the highest positive/negative ratio and the lowest intraassay standard deviation. Optimal conditions for each step in the ELISA have been determined. The assay proved to be specific, sensitive, and reproducible. Circulating ant…

Interaction of cimetidine with metoprolol, propranolol, or atenolol.

Production of interleukin-6, tumor necrosis factor α and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients

Production of interleukin-6, tumor necrosis factor α and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients. In patients with chronic renal failure alterations in monokine production are a common feature. Their clinical relevance has not yet been proven. We show here a correlation between an overproduction of interleukin-(IL)-6 and tumor necrosis factor alpha (TNFα) upon stimulation with LPS by mononuclear cells in vitro and the clinical grade of immunodeficiency found in these patients. Higher levels of IL-6 and TNFα were correlated with an immunocompromized state, that is, non-responsiveness to hepatitis B vaccination, whereas patients with…

Hepatitis G virus: an old, but newly discovered hepatotropic virus--is it of interest for the nephrologist?

Hepatitis B vaccination and interleukin 2 receptor expression in chronic renal failure

Hepatitis B vaccination and interleukin-2 receptor expression in chronic renal failure. Only 50 to 60% of dialysis patients develop anti-HBs antibodies following hepatitis b vaccination. The nonre-sponder state correlates with impaired monocyte function, decreased interleukin-2 (IL-2) production of T cells, and an upregulation of the IL-2 receptor system. In the present study we examined anti-HBs production after hepatitis B vaccination and the in vitro expression of IL-2 receptors in nondialyzed patients with various degrees of chronic renal failure. Forty-four patients with impaired renal function were immunized with 20 µg recombinant hepatitis B vaccine and boostered after one and six mo…