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Kurt Derfler

Publications and source records attributed to Kurt Derfler.

At least 19 recordsLinked to original sources
PubMed2005

Peritransplant immunoadsorption: a strategy enabling transplantation in highly sensitized crossmatch-positive cadaveric kidney allograft recipients.

BACKGROUND: Kidney transplant recipients with a current positive complement-dependent cytotoxicity crossmatch (CDCXM) are at high risk for hyperacute rejection and graft loss. Immunoadsorption (IA) represents an efficient strategy to remove donor-specific alloantibodies. In this analysis, we evaluated effectiveness of peritransplant IA as an anti-humoral strategy to overcome a current positive CDCXM in presensitized renal allograft recipients. METHODS: Between 1999 and 2003, 40 high risk cadaveric kidney allograft recipients (median CDC panel reactive antibody [PRA] level, 77%; number of retransplants, n = 38) were subjected to peritransplant IA with protein A (one pretransplant IA session followed by a course of repeat posttransplant IA sessions) in addition to preemptive antilymphocyte antibody therapy. RESULTS: In nine of these patients, a current positive CDCXM was rendered negative by a single pretransplant IA session. Thirty-one recipients had a negative CDCXM already before pretransplant IA. No difference in graft survival was found between CDCXM-positive and CDCXM-negative recipients (3-year graft survival, 78% vs. 71%, P = 0.6). Comparable rates of immunological graft loss at 3 years were observed (11% vs. 13%, P = 0.8). Patient groups did not significantly differ with respect to median serum creatinine at 1 year (1.23 mg/dL [CDCXM-positive] vs. 1.57 mg/dl [CDCXM-negative], P = 0.07) and at the end of follow-up (median 32 months; 1.19 mg/dL vs. 1.63 mg/dL, P = 0.06). Moreover, patient groups showed similar rates of biopsy-proven cellular rejection (11% vs. 20%) or C4d-positive graft dysfunction (33% vs. 32%). CONCLUSION: Our results demonstrate that peritransplant IA enables successful cadaveric kidney transplantation in the context of a positive CDCXM.

Adult↗
PubMed2005

The course of anticardiolipin antibody levels under immunoadsorption therapy.

BACKGROUND: The emergence of anticardiolipin antibodies in patients with systemic lupus erythematosus is a serious occurrence in regard to a high risk for thrombosis and thromboembolic complications, fetal loss, and renal insufficiency. In an observational analysis, we studied anticardiolipin antibodies during immunoadsorption therapy. METHODS: We analyzed the magnitude and time course of serum concentrations of the immunoglobulin G (IgG) and IgM subtypes of anticardiolipin antibodies (CIgG and CIgM) along with IgG and IgM, antinuclear antibodies, and antibodies to double-stranded DNA before and after single immunoadsorption sessions and their long-term course in 11 patients with systemic lupus erythematosus. RESULTS: Single immunoadsorption sessions (n = 842) led to a rapid decline in CIgG and CIgM levels by 62.94% +/- 21.60% and 42.02% +/- 22.14%, respectively (P < 0.0001), along with a corresponding decline in serum levels of antinuclear antibodies (65.04% +/- 18.83%), antibodies to double-stranded DNA (64.67% +/- 21.20%), IgG (58.11% +/- 16.84%), and IgM (32.15% +/- 15.58%). Reduction rates of CIgG and CIgM levels were greater when high initial concentrations (P < 0.0001) and low IgG levels (P < 0.0001) were present. Mean reductions in pretreatment values of CIgG and CIgM during 6 months of immunoadsorption therapy were 42.85% +/- 39.94% and 29.39% +/- 70.41% (mean number of sessions/patient = 21.55) and for the 1-year period were 63.20% +/- 22.49% and 58.05% +/- 40.16% (mean number of sessions/patient = 30.46). CONCLUSION: We observed that immunoadsorption therapy is an effective method to reduce anticardiolipin antibody levels rapidly and keep them at a low level in the long term.

Abortion, Habitual↗
PubMed2005

Citrate kinetics in patients receiving long-term hemodialysis therapy.

BACKGROUND: Regional anticoagulation using sodium citrate is used increasingly in hemodialysis patients at high risk for bleeding. However, citrate metabolism has never been evaluated systematically in hemodialysis patients, and it remains to be shown that citrate is cleared adequately in the presence of renal dysfunction. This study compares the pharmacokinetics of citrate in hemodialysis patients with minimal residual function with that in patients with normal renal function. METHODS: Long-term hemodialysis patients (n = 7) and patients without renal failure (n = 11) were investigated during routine immunoadsorption treatment by using a standardized citrate infusion protocol. Serial analysis of blood samples was performed before, during, and up to 120 minutes after citrate infusion (0.33 mmol/kg/h). Citrate plasma concentrations were measured colorimetrically. In addition, ionized calcium, pH, and bicarbonate were measured by using a blood gas analyzer. RESULTS: Basal (0.09 +/- 0.03 versus 0.12 +/- 0.03 mmol/L; P = not significant) and peak citrate concentrations were similar in both groups (1.24 +/- 0.42 versus 1.19 +/- 0.33 mmol/L; P = not significant). Citrate clearance was similar in patients with renal failure (0.31 +/- 0.06 L/min) and controls (0.35 +/- 0.11 L/min; P = 0.47). Effects on pH were minimal and did not differ between groups. No patient developed complications from citrate infusion. CONCLUSION: Compared with controls, citrate clearance and metabolism in long-term hemodialysis patients is not impaired, and no significant acid-base disorder occurred during citrate anticoagulation. From these data, it is tempting to conclude that citrate anticoagulation can be used safely in patients with chronic renal failure on regular hemodialysis therapy.

Acid-Base Imbalance↗
PubMed2004

Immunoadsorption (IAS) as a rescue therapy in SLE: considerations on safety and efficacy.

OBJECTIVE: In SLE, extracorporeal procedures aiming at reduction of immunoglobulin (Ig) and immune complexes (IC) are used as a rescue therapy. Plasma exchange (PE) has not been proven overall effective in SLE, and long-term treatment in particular has been associated with severe bacterial and viral infections. Immunoadsorption (IAS), in contrast, selectively removes Ig and IC and may thus be safer. We therefore investigated the rate of infections in SLE patients who were undergoing long-term IAS. METHODS: 16 SLE patients were treated with > or = 10 courses of IAS, and nine patients with highly active disease received pulse cyclophosphamide (IVCP) therapy in parallel. We retrospectively analysed the records of all these patients for the occurrence of infections. Patients receiving IAS therapy plus IVCP were compared with 25 patients with similarly active disease treated with standard IVCP therapy within the same observation period. Patients receiving IAS without additional IVCP were compared with patients with similarly moderate disease activity receiving neither IAS nor IVCP. RESULTS: No potentially life-threatening viral infection occurred in IAS-treated patients and episodes of herpes zoster were equally distributed. No severe infection was observed during IAS without concomittant cyclophosphamide. As expected, more patients with highly active disease receiving IVCP experienced infections than those with less active disease (16 of 34 [47%] vs. 2 of 22 [9%], p < 0.04). On comparing the two groups with highly active disease, infections were similar (IAS+IVCP: 3 of 9 patients [33%], IVCP only: 5 of 25 [20%]), but one patient receiving IAS+IVCP died of septicaemia. Disease activity significantly decreased in both groups treated with IAS. CONCLUSION: IAS has an acceptable safety profile with regard to severe infections and appears safe with regard to severe viral disease. Highly active disease and IVCP therapy increase the risk of severe infections in SLE.

Adolescent↗
PubMed2004

Effects of LDL-immunoapheresis on plasma concentrations of vitamin E and carotenoids in patients with familial hypercholesterolemia.

Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment.

Adult↗
PubMed2004

Mercury exposure in protein A immunoadsorption.

BACKGROUND: Immunoadsorption is increasingly used to treat antibody-mediated autoimmune diseases. To prevent microbial growth during storage, reusable protein A-Sepharose gel columns are primed with ethyl mercury thiosalicylate (thiomersal, 0.1% solution) and rinsed with phosphate buffer before use. In this study, we tested the hypothesis of systemic mercury exposure in protein A immunoadsorption. METHODS: Whole blood mercury levels were measured by atomic absorption spectroscopy before and after protein A immunoadsorption (11 patients, 26 treatments), anti-IgG immunoadsorption (eight patients, 13 treatments) and LDL apheresis (DALI and Therasorb systems; nine patients, 14 treatments). RESULTS: Patients treated with protein A immunoadsorption had significantly elevated baseline mercury levels compared with the other groups, which were not different from healthy controls. Following protein A immunoadsorption, mercury levels increased from 5.9+/-1.4 microg/l (mean+/-SEM, normal, <5 microg/l) to 32.3+/-5.7 microg/l, P<0.001). In one intensively treated patient, acute neurological toxicity developed at a mercury level of 107 microg/l. Symptoms abated slowly and did not recur after switching to a thiomersal-free system and chelation therapy. No mercury release to patients occurred in anti-IgG immunoadsorption or LDL apheresis treatments. CONCLUSION: This preliminary report suggests that protein A immunoadsorption columns primed with thiomersal during storage may cause a sustained increase of systemic mercury concentrations, which exceed current safety recommendations in a proportion of patients. Considering the potential for mercury-induced toxicity, every effort should be undertaken to reduce systemic mercury exposure, either by adding chelators to the rinsing solution or ideally by replacement of thiomersal.

Adult↗
PubMed2004

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients.

BACKGROUND: Iron deficiency and anemia are commonly encountered in patients with autoimmune diseases undergoing immune apheresis. This makes erythropoietin and iron substitution necessary in most patients. However, intravenous iron therapy may result in an increase of potentially toxic nontransferrin-bound iron. METHODS: We examined the effect of 50 mg or 100 mg of iron (III) sucrose on bleomycin-detectable iron (BDI) in immune apheresis patients. Six patients with autoimmune disorders and normal kidney function were enrolled. Before and after the injection of 50 mg or 100 mg of iron (III) sucrose, BDI was measured in serum samples at five different time points. RESULTS: There was no BDI traceable before injection of iron (III) sucrose. BDI was present in serum of all patients after the administration of 100 mg of iron (III) sucrose in concentrations up to 0.49 micromol/L. In contrast, only one patient showed BDI at a concentration of 0.16 micromol/L after the administration of 50 mg of iron (III) sucrose. CONCLUSION: We conclude that if parenteral iron is administered after apheresis treatment, despite the equal tolerability, use of 50 mg of iron (III) sucrose is superior to 100 mg of iron (III) sucrose in avoiding the formation of potentially toxic nontransferrin-bound iron.

Adult↗
PubMed2003

Flow cytometry based detection of HLA alloantibody mediated classical complement activation.

Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) testing is used to assess recipient presensitization and post-transplant alloantibody formation in transplant recipients. However, CDC test results can be affected by false-positive reactions brought about by autoantibodies or antilymphocyte reagents. As an alternative to the CDC-PRA assay, detection of HLA alloantibodies using HLA antigen-coated microbeads (FlowPRA test) was recently established. FlowPRA testing, however, does not distinguish between (presumably more harmful) complement-fixing and noncomplement-fixing alloantibodies. In this study, we established a novel assay allowing flow cytometric detection of HLA alloantibody dependent classical complement activation using the FlowPRA test. For the detection of complement activation, FlowPRA beads were incubated with sera from highly sensitized dialysis patients (CDC-PRA reactivity >60%) and then stained for C4 (C4d, C4c) and C3 (C3d, C3c) fragments, as well as C1q deposition using indirect immunofluorescence. We demonstrate alloantibody induced induction of C4 fragment, and in parallel C1q deposition to HLA class I or class II beads. As shown by immunoblotting, C4 staining was not due to the presence of preformed C4 fragment-IgG/M complexes. Indeed, C4 fragment deposition in our in vitro system was demonstrated to result from de novo complement activation. First, inactivation of C4 by treatment of sera with methylamine, which inhibits cleavage of the internal thioester, completely abolished C4 fragment deposition. Second, C4 fragment deposition was not observed in the evaluation of C4-free immunoadsorption eluates obtained from highly sensitized dialysis patients. After supplementation with complement, however, eluates induced C4 deposition. Deposition of C4 split products and C1q was temperature-dependent with maximum binding after incubation at 4 degrees C for 60 min. In contrast, maximum C3 fragment deposition was found at 37 degrees C. At this temperature, C3 deposition occurred in an alloantibody and C4-independent fashion, presumably as a result of alternative complement activation. In summary, we describe a novel cell-independent and easy-to-perform PRA test that permits flow cytometry based detection of alloantibody induced classical complement activation. Future studies will have to evaluate its possible relevance as an alternative to CDC-PRA testing in clinical transplantation.

Case-Control Studies↗
PubMed2003

Pemphigoid gestationis: treatment with immunoapheresis.

BACKGROUND: Pemphigoid (herpes) gestationis is a rare blistering disease of pregnancy. Topical and systemic corticosteroids and antihistamines are usually sufficient for treatment. CASE REPORT: A patient suffering from severe, therapy-resistant pemphigoid gestationis was successfully treated with the additional use of six sessions of immunoapheresis. Systemic corticosteroids could be tapered and serum autoantibody levels to bullous pemphigoid antigen 2 (BPAG2 = BP180) significantly dropped during this treatment. CONCLUSION: Immunoapheresis represents a helpful therapeutic option with few side effects for severe cases of pemphigoid gestationis, unresponsive to conventional treatment.

Adrenal Cortex Hormones↗
PubMed2003

Removal of persisting isohaemagglutinins with Ig-Therasorb immunoadsorption after major ABO-incompatible non-myeloablative allogeneic haematopoietic stem cell transplantation.

BACKGROUND: Major ABO-incompatibility can be associated with haemolysis, prolonged red cell aplasia (PRCA) and higher peri-transplant mortality resulting from organ toxicity after conventional and non-myeloablative allogeneic haematopoietic stem cell transplantation. Different therapeutic strategies have been developed to allow erythroid reconstitution in these patients. METHODS: We present three patients, who developed PRCA after non-myeloablative allogeneic haematological stem cell transplantation for haematological malignancies. The patients were treated with Ig-Therasorb immunoadsorption (five treatments per week) to remove persisting incompatible isohaemagglutinins. RESULTS: Two patients became transfusion independent after 12 and 14 treatments. In one patient, however, no reduction of the isohaemagglutinin titres could be observed after 25 treatments, probably due to persistence of his underlying disease. CONCLUSIONS: Although Ig-Therasorb immunoadsorption was effective in only two patients, it seems to be a promising therapeutic option for patients with PRCA after allogeneic non-myeloablative haematological stem cell transplantation.

ABO Blood-Group System↗
PubMed2002

A case of severe C4d-positive kidney allograft dysfunction in the absence of histomorphologic features of rejection.

Acute antibody-mediated (humoral) renal allograft rejection has emerged as a clinicopathological entity that carries a poor prognosis. Its diagnosis is based on typical pathohistologic features, serologic detection of donor-specific alloantibodies and the immunohistochemical finding of endothelial deposits of the complement split product C4d. We herein report a case of severe antibody-mediated graft injury after spousal-donor kidney transplantation. Despite an increased risk for humoral presensitization in the female recipient (three previous pregnancies), donor-specific alloantibodies were not detectable before transplantation. After initial graft function, severe graft dysfunction occurred one week after transplantation. A renal biopsy revealed no histomorphologic features of rejection. However, immunohistochemical detection of diffuse C4d deposits along peritubular capillaries suggested acute humoral rejection. The diagnosis of antibody-mediated rejection was confirmed by the detection of de-novo production of anti-donor alloantibodies. Graft dysfunction was resistant to high dose steroids or antilymphocyte antibody therapy. However, a recovery of graft function could be achieved by antibody elimination using immunoadsorption therapy. This case reinforces the high diagnostic value of C4d staining. In severe graft dysfunction humoral immune mechanisms should be considered, even when histopathologic features of humoral rejection are completely absent.

Adult↗
PubMed2002

Influence of plasma immunoglobulin level on antibody synthesis.

In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with immunoadsorption (IA) therapy. Specific and bulk immunoglobulin levels were obtained simultaneously. The mean serum flc concentration increased to the preapheresis value within 1 day and remained unchanged thereafter. Total immunoglobulin G (IgG) and specific antibody concentrations increased to pretreatment values in 88% and 43% of the patients, respectively, and remained below the original values in the others. In conclusion, the lack of increased flc synthesis after IA confirms the absence of a feedback mechanism regulating antibody synthesis. The restoration of serum IgG levels after IA, therefore, does not result from increased antibody synthesis but is probably related to changes of catabolism and immunoglobulin backflow.

Adult↗
PubMed2002

Severe 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication: kinetics and trials to enhance elimination in two patients.

In spring 1998, two women were diagnosed with severe 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication. Over the following 3 years, TCDD levels were monitored under various attempts to enhance its elimination, and the half-lives were evaluated. Olestra, a non-digestible, non-absorbable dietary fat substitute, was continuously administered to the patients either as pure substance or in potato-chips. Additionally, in the more severely contaminated patient, we studied whether low-density lipoprotein (LDL)-apheresis, an extracorporeal means of blood lipid elimination, was effective in reducing the TCDD body burden. The blood concentrations initially measured in spring 1998 were 144,000 pg/g blood fat in patient 1 and 26,000 pg/g in patient 2, the highest levels ever measured in adults. In March 2001, concentrations in blood fat were 35,900 and 9,500 pg/g, corresponding to overall elimination half-lives of 560 days (1.5 years) in patient 1 and 1050 days (2.9 years) in patient 2, which are considerably shorter than median values of 7-9 years reported for background and moderate exposure levels. Calculations of the TCDD half-lives and measurements of TCDD elimination via different routes allowed the calculation of an unidentified route of elimination, representing 78 and 62% of the overall elimination in patient 1 and 2, respectively, probably due to an induced hepatic metabolism caused by the high TCDD exposure. As previously reported, administration of olestra was found to be effective in increasing the fecal excretion of TCDD. Due to the short half-lives in our patients, the effect of olestra on the overall elimination was relatively small, but is expected to be much greater for 'normal' half-lives. LDL-apheresis was shown to eliminate TCDD, corresponding to the eliminated blood fat. When employed twice a week, the amount of TCDD excreted by this method was comparable to fecal excretion. In view of costs and time involved, LDL-apheresis does not seem to be justified for enhancement of TCDD elimination.

Adult↗
PubMed2002

Long-term treatment of myasthenia gravis with immunoadsorption.

Acute treatment of myasthenic crisis with immunoadsorption (IA) or plasma exchange is well established. The efficiency of chronic apheresis therapy in myasthenia gravis (MG), however, and its efficacy in reducing concomitant potentially harmful immunosuppressive therapy, is unknown. We treated 13 patients with therapy-resistant MG or severe steroid or azathioprine therapy-related side effects, or both, with long-term IA [median, 38 (range: 16-59) months]. IA was performed every second day until partial remission was achieved (modified Osserman score <2). Subsequently, oral immunosuppressive therapy was reduced and the frequency of IA adapted to the clinical symptoms. After initiation of IA the mean (SEM) Osserman score decreased from 3.23 +/- 0.12 to 1.23 +/- 0.08 within 1 month (P < 0.01). Mean azathioprine dose was reduced concomitantly from 89 +/- 9.4 mg/day to 56 +/- 11 mg/day (P < 0.05), and mean prednisolone dose from 41 +/- 7.6 mg/day to 22 +/- 8.5 mg/day (P < 0.05). After 36 months the number of IA-sessions/month had been reduced from 4.81 +/- 0.24 to 2.64 +/- 0.4 (P < 0.05), the mean azathioprine dose to 25 +/- 17 mg/day and the mean prednisolone dose to 9 +/- 3.6 mg/day. Six out of thirteen patients were weaned from IA after a median of 33 (range, 16-50) months and a decrease of the Osserman score to 0.33 +/- 0.33. In these patients MG remained stable during a follow-up period of 28 (range, 16-38) months. We conclude that long-term IA enables the reduction of oral immunosuppressants in patients with contraindications or resistance to steroid and azathioprine therapy. Furthermore, almost 50% of the patients can be weaned from IA with then substantial lower need of further immunosuppressive therapy.

Adult↗
PubMed2002

Treatment of systemic lupus erythematosus by immunoadsorption in a patient suffering from tuberculosis.

We report on a 40-year-old man, admitted with fever and weight loss, in whom systemic lupus erythematosus (lupus nephritis World Health Organization type IV) and concomitant acute lung tuberculosis were diagnosed. Conventional treatment of diffuse proliferative nephritis with cytotoxic drugs was thought to be too dangerous in the presence of active tuberculosis. A combination of immunoadsorption and steroids was instituted for the treatment of systemic lupus erythematosus. Antibodies against double-stranded DNA decreased, and proteinuria decreased from 10 g/24 hours to less than 1 g/24 hours. Tuberculosis was treated initially with quadruple-drug therapy, then a triple-drug protocol. Primarily enlarged lymph nodes decreased to normal size after 3 months. The combined treatment modality of steroids and immunoadsorption was effective and safe, even in this patient with active tuberculosis.

Administration, Oral↗
PubMed2002

Atorvastatin in low-density lipoprotein apheresis-treated patients with homozygous and heterozygous familial hypercholesterolemia.

To further reduce low-density lipoprotein-cholesterol (LDL-C), atorvastatin treatment was investigated in patients with homozygous (n = 4) and heterozygous (n = 10) familial hypercholesterolemia (FH) undergoing LDL-apheresis. After a wash-out period of 4 weeks, atorvastatin therapy was administered in escalating doses (10 up to 80 mg/d). LDL-apheresis was performed at weekly intervals during the entire study period. The LDL-C concentration decreased from 240 +/- 35 mg/dL after the wash-out period to 206 +/- 63 mg/dL during treatment with 10 mg atorvastatin. Four weeks of treatment with 80 mg atorvastatin resulted in an additional 24% (P <.05) reduction in LDL-C. LDL-C increased from 28.8 +/- 14.2 mg/dL immediately after apheresis to 156.6 +/- 25.5 mg/dL at day 7. LDL-C values remained below the recommended target range for an extended duration of 48 hours in atorvastatin-treated patients, but not in those without concomitant lipid-lowering drug therapy. The levels of high-density lipoprotein-cholesterol (HDL-C) and plasma fibrinogen were unchanged during the entire study period. No adverse events were observed with atorvastatin treatment. Finally, high-dose atorvastatin therapy resulted in a 40% reduction in LDL-apheresis sessions in these patients. Our results show that LDL-C reduction by atorvastatin is a safe and effective therapy in LDL-apheresis patients with severe heterozygous or homozygous FH.

Adolescent↗