Marten Trendelenburg

Universitätsspital Basel, Bâle, Basel-City, Switzerland

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Publications (64)234.83 Total impact

  • Kf Koenig, C Ribi, M Radosavac, H Zulewski, M Trendelenburg
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    ABSTRACT: Systemic lupus erythematosus (SLE) is associated with considerable cardiovascular morbidity that has not yet been directly compared with other diseases with known cardiovascular risk.
    Lupus 09/2014; · 2.48 Impact Factor
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    ABSTRACT: The role of complement has been demonstrated in experimental models of neuromyeltis optica (NMO), however, only few studies have analysed complement components longitudinally in NMO patients. We measured serum or plasma concentrations of anti-C1q antibodies and complement split products C3a, C4a and soluble C5b-9 in patients with NMO, multiple sclerosis and healthy controls. NMO patients had higher levels of C3a and anti-C1q antibodies than healthy controls. C3a levels correlated with disease activity, neurological disability and aquaporin-4 IgG in NMO patients suggesting a role of the alternative pathway of complement in the pathogenesis of NMO and supporting the strategy of therapeutic complement inhibition.
    Journal of Neuroimmunology 09/2014; · 2.79 Impact Factor
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    ABSTRACT: To describe disease characteristics and treatment modalities in a multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in Switzerland.
    Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 01/2014; 144:w13990. · 1.88 Impact Factor
  • Michael Osthoff, Marten Trendelenburg
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    ABSTRACT: Contrast-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL), a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R) injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.
    BioMed research international. 12/2013; 2013:962695.
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    ABSTRACT: Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12(th) gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3-78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery.
    PLoS ONE 12/2013; 8(12):e81755. · 3.53 Impact Factor
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  • Paula Scharein, Marten Trendelenburg
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    ABSTRACT: Reducing medical errors has become an international concern. Population-based studies consistently demonstrate inacceptable high rates of medical injury and preventable deaths. Thus, electronic critical incident reporting systems are now increasingly used in hospitals, predominantly in anesthesia. However, studies systematically analyzing critical incidents are scarce. Our aim was to describe content and causes of critical incidents in our Clinic for Internal Medicine. We retrospectively analyzed all critical incidents reported during a 54-months period. Between implementation and analysis, 456 incidents were reported anonymously in the commercially available platform-independent, web-based critical incident reporting system. All incidents were analyzed according to the reporting profession, time point during hospitalization process, content and potential causes.Most incidents occurred on medical wards (80%). The most frequent type of incidents was medication errors (62%). These incidents primarily occurred when prescribing and/or administering drugs (30% and 29% of medication errors respectively). So-called [single low-9 quotation mark]human errors', i.e. occurring without apparent external factor, were the most frequently indicated cause of critical incidents (56%) followed by insufficient communication (26%). These problems primarily occurred between different groups of health care professionals and between different departments. The described types and reasons of critical incidents remained stable during the observation period. The findings of our analysis of the character and type of critical incidents occurring in a tertiary care clinic for internal medicine reported in an anonymous, voluntary, electronic reporting system suggest that strategies to improve communication and medication delivery are most promising to avoid critical incidents.
    BMC Research Notes 07/2013; 6(1):276.
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    ABSTRACT: BACKGROUND: In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA. RESULTS: We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log(10) ng/mL increase (95% CI 0.73-1.45)) nor with ficolins (OR per log(10) ng/mL increase 0.66 (95% CI 0.28-1.52), 2.34 (95% CI 0.44-12.36), and 0.89 (95% CI 0.26-3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log(10) copies/mL; 95% CI 1.08-2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84-0.98). CONCLUSIONS: CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.
    PLoS ONE 01/2013; 8(1):e51983. · 3.53 Impact Factor
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    ABSTRACT: Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort. 246 patients with advanced non-dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥0.5 mg/dL or ≥25% within 48 hours) or cystatin C-based (increase of ≥10% within 24 hours) CIN. The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193-4471) vs. 1997 (IQR 439-3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels≤500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01). MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.
    BMC Nephrology 09/2012; 13:99. · 1.52 Impact Factor
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    ABSTRACT: Determination of disease activity of lupus nephritis remains challenging. Since cytokines play a role as inflammatory mediators extending renal injury, measuring serum cytokine levels might help in the clinical assessment of patients with lupus nephritis. Therefore, the aim of this study was to determine the diagnostic value of a panel of serum cytokines in patients with active lupus nephritis. In this prospective controlled multicenter trial, sera of 12 patients with active lupus nephritis were collected in a clinical routine setting at the time of renal biopsy and 6months afterwards. Fourteen patients with inactive systemic lupus erythematosus (SLE), and 14 healthy subjects were used as controls. Eleven cytokines (IL-4, IL-5, IL-6, IL-10, IL-12(p40), IL-12(p70), IL-18, TNF-α, TGF-β1, IFN-α2, IFN-γ) and two soluble receptors (IL-1ra and TNF-RII) were measured by cytokine multiplex assay. In inactive SLE patients, serum levels of IL-10, IL-12(p40), IL-18 and TNF-RII were increased compared to healthy controls. Active lupus nephritis was found to be associated with further increase of these cytokine levels. Follow-up measurements in clinical remission of lupus nephritis showed downregulation of increased cytokines to levels found in inactive SLE. Most strikingly, TNF-RII serum level were elevated in all patients with active lupus nephritis (p<0.001) and declined after clinical remission (p<0.0005). The cytokine multiplex assay used in our study allowed a fast and stable analysis of a panel of serum cytokines in a clinical routine setting. In addition, serum cytokines, especially TNF-RII, might be excellent markers of active lupus nephritis.
    Cytokine 07/2012; 60(2):410-6. · 2.87 Impact Factor
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    ABSTRACT: OBJECTIVES: Auto-antibodies against complement C1q strongly correlate with the occurrence of severe nephritis in systemic lupus erythematosus (SLE) patients. Identification of the C1q epitope(s) recognized by these auto-antibodies might lead to a better diagnostic assay and help elucidating the putative role of C1q and anti-C1q in SLE. METHOD: SLE patient derived anti-C1q Fabs were used in a micro-array based peptide scan to identify the peptide sequence recognized by anti-C1q. Anti-C1q Fab binding to the target peptide was further analyzed in real time (Biacore) and peptide-based ELISA's. RESULTS: A peptide scan of the collagen-like region of C1q identified two regions, one on the A-chain and one on the B-chain that are the target of the anti-C1q Fabs. Binding was confirmed by Biacore and showed nanomolar affinity. The A-chain derived peptide could specifically be detected in a peptide-based ELISA by SLE patients' sera. Competition experiments suggested that this peptide represents one of the major linear epitopes of C1q that is the target of anti-C1q in SLE. Serum antibodies from most SLE patients but not from healthy individuals specifically bound to this epitope. Binding to the peptide correlated with binding of the same sera to native C1q but was found to be more sensitive for the detection of lupus nephritis. CONCLUSION: We identified a major linear epitope of C1q that is the target of anti-C1q in SLE. The ELISA-based assay using this peptide was more specific and more sensitive than a conventional anti-C1q assay for the detection of SLE patients with active nephritis.
    Arthritis & Rheumatology 06/2012; · 7.48 Impact Factor
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    Clinical Immunology 05/2012; 144(1):80-2. · 3.77 Impact Factor
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    ABSTRACT: Cryoglobulinemia induces an immune complex-mediated glomerulonephritis that is characterized by the presence of large immune deposits, including complement C3 and C5b-9, marked macrophage influx and mesangial cell proliferation. The precise role of complement in cryoglobulin-induced glomerulonephritis in humans remains unclear, whereas in mice there has been evidence that complement activation might be a central factor favoring glomerular inflammation, particularly by the recruitment of neutrophils. We report on an exceptional case of cryoglobulin-induced glomerulonephritis in a patient with mixed essential cryoglobulinemia type II. The clinical features included relapsing proteinuria and renal function impairment that were controlled by plasmapheresis. Complement was low in plasma and two renal biopsies at 1-year interval showed prominent immunoglobulin and complement deposits, with unusual high numbers of neutrophils. In a 1-patient clinical trial, we tested whether the monoclonal anti-C5 antibody eculizumab would be sufficient to control renal function at the time of a relapse. Although during the initial weeks renal function was stabilized, slow increase in creatinine could not be controlled by this treatment, so that plasmapheresis was reinstituted. This result suggests that despite evidence for a role of complement in enhancing renal damage in this patient, other inflammatory processes dominated.
    Case reports in nephrology and urology. 01/2012; 2(1):38-45.
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    Marten Trendelenburg
    Arthritis & Rheumatology 01/2012; 64(1):324-5; author reply 325-6. · 7.48 Impact Factor
  • Nature medicine 12/2011; 17(12):1547-8; author reply 1548. · 28.05 Impact Factor
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    ABSTRACT: Background / Purpose: The aim of the study was to determine the association between anti CRP levels and the activity of lupus nephritis (LN). Main conclusion: The study was performed on 57 patients with Systemic Lupus Erythematosus (SLE) diagnosed according to ACR criteria and LN proved by renal biopsy. Levels of anti CRP antibodies were significantly higher in the patients with activity of LN (26.78 versus 7.5, respectively; p= 0.009). Anti-CRP antibodies did not occur in patients with inactive LN (p= 0.051). Additionally, levels of anti-CRP antibodies positively correlated with the activity of SLE as assessed by the SLEDAI score (Spearman 0.406, p= 0.002).In conclusion, serum levels of anti-CRP antibodies seem to be a useful laboratory marker of LN/SLE activity.
    48th Congress of the European Renal Association and European Dialysis and Transplant Association 2011; 08/2011
  • Molecular Immunology 08/2011; 48(14):1717-1718. · 3.00 Impact Factor
  • Molecular Immunology 08/2011; 48(14):1720-1721. · 3.00 Impact Factor
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    ABSTRACT: The Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment. In a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (<100 ng/ml) were subject to a considerably decreased risk of an unfavorable outcome three months after ischemic stroke (adjusted odds ratio 0.38, p<0.05) and showed smaller lesion volumes (mean size 0.6 vs. 18.4 ml, p = 0.0025). In contrast, no association of MBL concentration with infarction volume or functional outcome was found in the thrombolysis group. However, the small sample size limits the significance of this observation. MBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.
    PLoS ONE 06/2011; 6(6):e21338. · 3.53 Impact Factor
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    ABSTRACT: In systemic lupus erythematosus patients, a strong association between the occurrence of antibodies against complement C1q (anti-C1q) and lupus nephritis can be observed. However, the predictive value of anti-C1q titres for a renal flare remains to be determined. Increasing titres of anti-C1q before the occurrence of clinical apparent nephritis might not only serve as a clinical parameter but also indicate a direct pathogenic mechanism of anti-C1q. The aim of this study was to analyse the occurrence of anti-C1q before the onset of experimental lupus nephritis in MRL/MpJ +/+ mice and to correlate anti-C1q titres with the type and severity of glomerulonephritis (GN) developing at advanced age. As judged by a number of morphological and immunological analyses, GN in MRL/MpJ +/+ mice resembled human lupus nephritis and occurred in variable degrees of severity. We also observed an abundant and early presence of anti-C1q. However, anti-C1q neither correlated with overall survival nor with any histological marker of severity of GN. The absence of a correlation between the presence of anti-C1q and the occurrence of experimental lupus nephritis contradicts the hypothesis that anti-C1q are pathogenic. However, different pathogenic mechanisms of experimental lupus nephritis and human proliferative lupus nephritis cannot be excluded.
    Nephrology Dialysis Transplantation 04/2011; 26(4):1220-8. · 3.37 Impact Factor

Publication Stats

666 Citations
234.83 Total Impact Points

Institutions

  • 1999–2014
    • Universitätsspital Basel
      • • Klinik für Innere Medizin
      • • Klinik für Infektiologie & Spitalhygiene
      Bâle, Basel-City, Switzerland
  • 2000–2013
    • Universität Basel
      • Department of Biomedicine
      Bâle, Basel-City, Switzerland
  • 2011
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 2008–2010
    • Charles University in Prague
      • 1st Faculty of Medicine
      Praha, Praha, Czech Republic
  • 2009
    • University of Geneva
      • Department of Rehabilitation and Geriatrics
      Genève, GE, Switzerland
  • 2006
    • Belarus State Economic University
      Myenyesk, Minsk, Belarus
  • 2004
    • Imperial College London
      • Faculty of Medicine
      Londinium, England, United Kingdom
  • 2003
    • University of Bergen
      Bergen, Hordaland, Norway