Otto Traindl

Adverse effect of low-dose prophylactic human recombinant leukocyte interferon-alpha treatment in renal transplant recipients: cytomegalovirus infection prophylaxis leading to an increased incidence of irreversible rejections

Since infections with Herpetoviridae after kidney transplantation still remain a major clinical problem, we conducted a double-blind, placebo-controlled trial using low-dose recombinant interferon-alpha-2C (rIFNa2C) prophylaxis in 50 renal graft recipients im-munosupressed with cyclosporine and methylpredniso-lone. Ten patients were excluded from further analysis because of graft loss due to surgical complications, side effects of rIFNa2C, and because of lack of compliance. There was a significant difference in graft loss due to irreversible rejections between the verum and the placebo group (6 vs. 0; P< 0.05), whereas no difference was observed with regard to the occurrence of viral infections. We conclude, that low-dose rIFNa2C prophylaxis is harmful in renal allograft recipients treated with cyclosporine in view of the high incidence of irreversible transplant rejections without beneficial effects on the occurrence of viral infections.

Recombinant tissue plasminogen activator is a useful alternative to heparin in priming Quinton Permcath

Soft, cuffed, implantable central venous catheters such as the Quinton Permcath (Quinton Instrument Co, Seattle, WA) are increasingly used as permanent access in patients with end-stage renal disease. Their major limitations, besides infection, are thrombosis and inadequate blood flow. To prevent those complications, heparin is conventionally used for priming the Quinton Permcath between dialysis sessions. In this study, we compared recombinant tissue plasminogen activator (rTPA) with heparin for priming the Quinton Permcath in a prospective, randomized, crossover design. Twelve patients were randomly assigned to receive 2,000 IU of heparin or 2 mg of rTPA injected into each catheter lumen at the end of each dialysis session over a period of 4 months, followed by a switch to the other substance. Blood flow rate (flow), venous pressure (VP), and arterial pressure (AP) were monitored at each dialysis session hourly. Flow was significantly greater (P = 0.0001) with rTPA (mean +/- SD, 237.7 +/- 18.1 and 231.6 +/- 12.4 mL/min for the first and second 2 months, respectively) compared with heparin (208.5 +/- 10.1 and 206.9 +/- 14.2 mL/min for the first and second 2 months, respectively). VP was significantly less (P = 0.0001) with rTPA (135.4 +/- 8.2 and 140 +/- 15.2 mm Hg for the first and second 2 months, respectively) compared with heparin (160.5 +/- 16.1 and 159.2 +/- 20.7 mm Hg for the first and second 2 months, respectively). AP was significantly greater (P = 0.0002) with rTPA (-113.5 +/- 11.8 and -115.9 +/- 12.7 mm Hg for the first and second 2 months, respectively) compared with heparin (-136.5 +/- 23.3 and -134.7 +/- 25.8 mm Hg for the first and second 2 months, respectively). In addition, fewer complications (flow problems, clotting, and need for fibrinolysis) occurred in the rTPA period. These results show that rTPA is superior to heparin for priming the Quinton Permcath between hemodialysis sessions and can be used as a valuable alternative to conventional heparin in selected patients.

Reactive oxygen product formation by human neutrophils as an early marker for biocompatibility of dialysis membranes.

Production of reactive oxygen intermediates (ROI) by neutrophils (PMN) in vivo was examined by a whole blood assay using dichlorofluorescein‐diacetate (DCFH‐DA) in 10 patients each dialyser consecutively with two different dialyser membranes. Haemodialysis (HD) with cuprophan membrane (CM) led to a significantly (P < 0001) more pronounced ROI production by PMN (2.4 ± 0.5‐fold increase in Intracellular oxidation of DCFH‐DA) compared with HD with polysulfone membranes (PM; 1.5 ± 0.2‐fold). HD with CM induced a decrease in PMN count by about 90%, whereas PM induced a decrease by only 25% (P < 0.001). In CM patients maximal ROI production coincided with the nadir in PMN count. All patients dialysed with CM showed a clear increase in serum levels of Bb fragments. whereas PM‐dialysed patients did not. In this respect however, no clear time relationship was seen to the kinetics of ROI production, nor to the disappearance of neutrophils from the circulation valuating a direct effect of the dialysis membranes on PMN demonstrated that incubation of neutrophils with hollow fibres of the CM but not of the PM in the absence of plasma induces significant ROI production by PMN. Our study thus indicates that ROI production by PMN during HD correlates to membrane biocompatibility. Furthermore, one might speculate that also independently from but perhaps in addition to complement activation, reactive oxygen products arc critically involved in the generation of haemodialysis‐associated neutrophil emigration.

The effects of lisinopril on renal function in proteinuric renal transplant recipients.

Renal transplantation is frequently accompanied by systemic hypertenion. In the present study we evaluated the effect of 2.5 mg lisinopril in 12 hypertensive and proteinuric renal graft recipients with stable graft function over 3 months. Only patients with absence of renal artery stenosis, at least as judged by technetium-scan imaging, were included. Lisinopril was effective in lowering systemic blood pressure. Mean arterial pressure was unchanged despite reduction of concomitant anti-hypertensive medication. Mean serum creatinine was unchanged during the study (1.95±0.8 mg/dl in the pre-treatment period vs. 1.77±0.76 mg/dl in the intervention period, n.s.). Glomerular filtration rate remained stable (62.75±21.96 vs. 60.17±18.27 ml/min/1.73 m2, n.s.) whereas renal plasma flow increased (224.75±91.66 vs. 244.92±94.13 ml/min/1.73m2, P<0.01), leading to a drop in filtration fraction (31.4±12.4 vs. 26.8± 8.6, n.s.). Renal vascular resistance was significantly reduced following angiotensin-converting enzyme (ACE) inhibitor therapy (26447±14574 vs. 23425±12430 dyne sec cm-5/1.73 m2, P<0.01). Mean daily proteinuric decreased significantly (2.98±2.06 vs. 2.06±2.29 g, P<0.01) whereas in a group of patients with comparable blood pressure but without ACE inhibitor therapy and similar degree of proteinuria, 24-hr proteinuria remained stable. No severe side effects were observed—in particular, mean serum potassium showed only a slight increase and no clinically significant hy

Renal Allograft Arteriovenous Fistula due to Needle Biopsy with Late Onset of Symptoms – Diagnosis and Treatment

A post-biopsy arteriovenous (AV) fistula in a renal allograft was diagnosed using color-coded Doppler sonography. Because the patient was asymptomatic, no specific treatment was initiated. 15 months after the diagnosis was established, severe hematuria with obstruction of the bladder occurred. Angiography revealed a connection of the fistula to the renal pelvis. The patient was treated successfully by transarterial embolization of the fistula. As a conclusion, we suggest periodical follow-up examinations of asymptomatic AV fistulas in renal allografts using color-coded Doppler sonography during 3-6 months. When no spontaneous regression of the fistula can be observed, embolization therapy should be performed even when the fistula is asymptomatic, in order to prevent late onset of complications.

Esophageal tracheal combitube (ETC) for emergency intubation: anatomical evaluation of ETC placement by radiography.

The esophageal tracheal combitube (ETC) is designed for emergency intubation. The ETC is inserted blindly allowing ventilation after either esophageal or endotracheal placement. A special pharyngeal balloon serves to seal the upper airways. In 10 cardiac arrest patients, emergency intubation with the ETC was performed. Blood gas analyses showed adequate ventilation. Radiography proved correct placement of the proximal and distal balloons in accordance with design theory. Hyperinflation experiments documented expansion of the proximal balloon into the oral cavity rather than towards the epiglottis.

Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal antibody treatment

Cytokine release and clinical side effects resulting from the use of OKT3 and BMA 031 monoclonal antibodies in the treatment of kidney graft recipients were evaluated and compared. The rise observed in serum levels of interferon γ, TNFα, and IL-8 was similar after administration of either monoclonal antibody. Furthermore, both OKT3 and BMA 031 resulted in rapid disappearance not only of virtually all T cells, but also of substantial percentages of all major leukocyte populations from the circulation; this effect is probably due to cytokine release activating endothelial cells and thereby causing extravasation even of leukocytes not specifically recognized by the administered antibodies. Evidence has thus been obtained that BMA 031 is as potent as OKT3 in inducing unequivocal signs of T cell activationin vivo. However, while OKT3 therapy was accompanied by adverse side effects in our study as in previous ones, we saw no such reactions in any of the patients receiving BMA 031. This contrast might be due to different mechanisms of leukocyte activation possibly inducing other mediators in the case of OKT3, which then, in combination with the cytokines, could generate treatment-associated morbidity.

Atrial natriuretic peptide release in response to different positive end-expiratory pressure levels.

ObjectiveTo assess the influence of different positive end-expiratory pressure (PEEP) levels on plasma atrial natriuretic peptide concentrations. DesignProspective, randomized study. SettingIntensive care unit of a university hospital. PatientsTwenty-seven patients who were mechanically ventilated due to acute respiratory failure. InterventionNone. Measurements and Main ResultsThe patients were randomized into three groups: in each group, a defined PEEP level (5, 10, or 15 cm H2O, respectively) was applied, alternating with zero PEEP (0 cm H2O) in consecutive order (reversal experiment). Blood samples for the determination of atrial natriuretic peptide concentrations were drawn from the pulmonary artery and the radial artery catheters. There were no decreases in atrial natriuretic peptide concentrations with a PEEP of 5 cm H2O, but significant decreases could be shown for PEEP values of 10 and 15 cm H2O. The patients of all groups were subjected to PEEP levels of 5, 10, 15, and 20 cm H2O in randomized order (step experiment). The data demonstrated a significant inverse correlation between changes in PEEP levels and changes in plasma atrial natriuretic peptide concentrations. ConclusionThe data suggest that the release of atrial natriuretic peptide is influenced by a PEEP of≥10 cm H2O, while a PEEP of ≤5 cm H2O does not disturb this cardiac endocrine function. (Crit Care Med 1993; 21:343–347)

Treatment of Hyperlipidemic Kidney Graft Recipients with Lovastatin: Effect on LDL-Cholesterol and Lipoprotein (a)

An increased incidence of hyperlipidemia places kidney graft recipients at increased risk for cardiovascular disease and may contribute to a decline in graft function. A study was undertaken to evaluate the safety and efficacy of lovastatin in these patients. Twelve kidney graft recipients with stable graft function and a cholesterol (chol) level over 250 mg/dl (6.46 mmol/l) were included. The lipid-lowering treatment consisted of 20 mg lovastatin daily, and all patients received immunosuppression with ciclosporin (CS) and prednisolone. Total chol decreased by 27% (300 +/- 56 to 219 +/- 28 mg/dl; 7.76 +/- 1.45 to 5.66 +/- 0.72 mmol/l; p < 0.01), LDL-chol by 35% (220 +/- 38 to 143 +/- 17 mg/dl; 5.69 +/- 0.98 to 3.70 +/- 0.44 mmol/l; p < 0.01) and triglycerides by 33% (207 +/- 127 to 138 +/- 56 mg/dl; 2.36 +/- 1.44 to 1.57 +/- 0.64 mmol/l; p < 0.05). HDL-chol increased by 10% (57 +/- 11 to 63 +/- 13 mg/dl; 1.47 +/- 0.28 to 1.63 +/- 0.34 mmol/l; NS). The ratio of total chol/HDL-chol, a generally accepted risk predictor of atherosclerosis, fell from 5.4 +/- 1.3 to 3.3 +/- 1.2, p < 0.01. Lipoprotein (a) [lp(a)], an independent risk predictor for atherosclerosis, was also evaluated at baseline and after 6 months of lovastatin treatment and showed a decrease of 39% (32.9 +/- 27.6 to 19.9 +/- 22.9 mg/dl; 0.85 +/- 0.71 to 0.51 +/- 0.59 mmol/l; p < 0.05). No adverse side effects were seen at this dosage, and hepatic and renal parameters remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced blood coagulation and enhanced fibrinolysis during hemodialysis with prostacyclin

In the present study the effect of unfractionated heparin (UFH) (Liquemin, 750-1000 IU/h), low molecular weight heparin (LMWH) (Fragmin, 3000-7250 IU bolus), and prostacyclin (Flolan, 5 ng/kg body weight/min) on the activation of blood coagulation and fibrinolysis, induced by polysulfone membrane dialyzers during hemodialysis, was compared. Plasma levels of thrombin-antithrombin III complex (TAT), fibrin split product D-dimer, and plasmin-plasmin inhibitor-complex (PPI) were measured in the arterial and venous line of the dialyzer at the beginning and at 10, 60, 120, and 180 minutes of hemodialysis. Five patients on chronic hemodialysis treatment were investigated in a cross over study. Clinically all three anticoagulation regimen were sufficient for hemodialysis treatment. Using UFH or LMWH TAT, PPI, and D-dimer levels were similar in the venous and the arterial line of the dialyzer. However, during prostacyclin treatment the levels of these activation markers were significantly higher in the venous line. Based on these data the dialyzer membrane can be considered as a site of activation of blood coagulation and of fibrinolysis during anticoagulation with prostacyclin in hemodialysis.