Kirsten de Groot

University of Virginia, Charlottesville, Virginia, United States

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Publications (94)599.22 Total impact

  • DMW - Deutsche Medizinische Wochenschrift 10/2014; 139(44):2248-53. DOI:10.1055/s-0034-1387327 · 0.54 Impact Factor
  • Ulf Schönermarck · Wolfgang L Gross · Kirsten de Groot ·
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    ABSTRACT: Antineutrophil cytoplasmic autoantibody (ANCA)-associated diseases are small-vessel vasculitides, encompassing granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Once considered life-threatening diseases, the introduction of stage-adapted immunosuppressive therapy and medications with decreased toxicity has improved patients' survival. Treatment is biphasic, consisting of induction of remission (3-6 months) for rapid control of disease activity and maintenance of remission (at least 18 months) to prevent disease relapse using therapeutic alternatives that have reduced toxicity. This Review summarizes current treatment strategies for these diseases, with a special focus on long-term follow-up data from key randomized controlled trials and new developments in remission induction and maintenance therapy. Current treatment strategies have substantial short-term and long-term adverse effects, and relapses are frequent; thus, less-toxic and more-effective approaches are needed. Moreover, the optimal intensity and duration of maintenance therapy remains under debate. Clinical trials have traditionally considered ANCA-associated vasculitides as a single disease entity. However, future studies must stratify participants according to their specific disease, clinical features (different types of organ manifestation, PR3-ANCA or MPO-ANCA positivity) and disease severity.
    Nature Reviews Nephrology 11/2013; 10(1). DOI:10.1038/nrneph.2013.225 · 8.54 Impact Factor
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    ABSTRACT: Objectives: To investigate the nature of the relationship between proteinase 3 anti-neutrophil cytoplasm autoantibody (PR3-ANCA) and relapse in patients with early systemic granulomatosis with polyangiitis (Wegener's) (GPA). Methods: Clinical data from 16 relapsing and 12 non-relapsing patients with early systemic GPA from a randomised clinical trial were correlated to monthly PR3-ANCA values over 18 months. Each sample was examined using 9 different enzyme-linked immunosorbent assays (ELISAs) to ensure reliability of ANCA results. PR3-ANCA peaks were identified by the highest sum of logarithmic transformation values from all assays in samples after remission. Results: A PR3-ANCA peak was identified in all relapsing and non-relapsing patients and coincided with relapse in all 14 evaluable relapsing patients. The monthly increment before the peak, however, was similar in relapsing and non-relapsing patients in all assays. Increments from remission to peak were higher in relapsing patients in 2/9 assays. PR3-ANCA values at entry and peak PR3-ANCA values were higher in relapsing patients in 3/9 and 2/9 assays, respectively. However, large overlaps of PR3-ANCA values prevented a distinction between relapsing and non-relapsing patients. The median time to reach peak values was 14 months in relapsing and 12 months in non-relapsing patients with scheduled termination of treatment at 12 months. Conclusions: The predictive value for relapses of PR3-ANCA determinations confirm and extend previous reports. Although all relapses were related to PR3-ANCA increases, reduction or withdrawal of immunosuppression without relapse was also related to increases and may explain the lack of predictive value of sequential PR3-ANCA determinations.
    Clinical and experimental rheumatology 02/2013; 31(1 Suppl 75). · 2.72 Impact Factor
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    Arthritis & Rheumatology 11/2012; DOI:10.1002/art.37794 · 7.76 Impact Factor
  • Kirsten de Groot ·
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    ABSTRACT: Glomerulonephritis (GN) is a common manifestation of the antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASV), which include granulomatosis with polyangiitis and microscopic polyangiitis. The level of renal involvement at presentation is highly predictive of survival and should be assessed early so that kidney function can be preserved. AASV patients with urinary sediment but normal function have a twofold greater risk of death than those with no renal involvement. Those with impaired renal function at diagnosis have a fivefold greater risk of death. Renal vasculitis is most prevalent in older patients, who have more severe disease and poorer prognoses. Renal biopsy not only establishes diagnosis but provides information on severity of renal-function impairment and prognosis. Induction of remission with cyclophosphamide is standard treatment. For patients with crescentic, rapidly progressive GN, adjunctive plasma exchange can promote renal recovery. Renal failure occurs in one-fourth of AASV patients after 3 to 4 years; 60% of patients receiving dialysis for acute GN can recover independent renal function. Renal transplant patients with vasculitis fare as well as renal transplant patients without vasculitis. Lastly, renal vasculitis is an independent risk factor for cardiovascular events.
    Cleveland Clinic Journal of Medicine 11/2012; 79 Suppl 3(Suppl_3):S22-6. DOI:10.3949/ccjm.79.s3.05 · 2.71 Impact Factor
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    ABSTRACT: The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide (CYC) as remission-inducing treatment for patients with newly diagnosed early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Duration of relapse-free survival was longer among CYC-treated patients than among MTX-treated patients during short-term followup. The aim of the present study was to describe the long-term outcome in patients enrolled in the randomized clinical trial. Outcome questionnaires were sent to investigators who had recruited patients for the NORAM trial. Patients treated with MTX for induction of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect to immunosuppressive therapy during followup, relapse-free survival, mortality, and occurrence of other clinical events. The median duration of followup was 6 years (range 0.1-10.8 years). One patient developed end-stage renal disease, and 11 died. The number of patients affected by serious infection, malignancy, or severe organ failure did not differ between treatment groups, and no difference in survival rate was observed. The duration of corticosteroid therapy was longer in the MTX group during the 18 months of the trial (P = 0.005). During subsequent followup, patients who were in the MTX group in the NORAM trial received corticosteroids, CYC, and other immunosuppressive agents (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively). The cumulative relapse-free survival tended to be lower in the MTX group (P = 0.056). In the NORAM cohort, no difference in occurrence of major adverse events was observed between treatment groups during long-term followup. However, first-line treatment with MTX was associated with less effective disease control than CYC-based induction therapy.
    Arthritis & Rheumatology 10/2012; 64(10):3472-7. DOI:10.1002/art.34547 · 7.76 Impact Factor
  • K de Groot · E Märker-Hermann ·
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    ABSTRACT: Secondary vasculitis is a form of vasculitis for which an underlying disease is known. Diseases associated with secondary vasculitis include infections, drug hypersensitivity, malignancy, rheumatoid arthritis, collagen vascular disease and sarcoidosis. Moreover, there are numerous conditions that can mimic vasculitis clinically, in laboratory testing, radiographically and in histopathology. It is evident that distinguishing primary vasculitis from secondary vasculitis and also vascular inflammation from non-vasculitic disorders (vasculitis mimics) has significant therapeutic implications.
    Zeitschrift für Rheumatologie 09/2012; 71(9). DOI:10.1007/s00393-012-0986-8 · 0.61 Impact Factor
  • B. Hellmich · K. de Groot ·
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    ABSTRACT: Kryoglobulinämische Vaskulitiden sind immunkomplexvermittelte Vaskulitiden kleiner und mittelgroßer Gefäße und werden v. a. im Rahmen einer Hepatitis-C-Infektion oder Kollagenose gesehen. Die typische Symptomatik umfasst eine Purpura der Haut, Arthralgien und Polyneuropathie, häufig gekoppelt mit einer membranoproliferativen Glomerulonephritis. Neuerdings existieren Klassifikationskriterien, die laborchemische und klinische Kriterien umfassen, nachdem Kryoglobuline im Serum nachgewiesen wurden. Therapeutisch steht die Behandlung der zugrunde liegenden Erkrankung im Vordergrund, d. h. in den meisten Fällen die antivirale Therapie der ursächlich auslösenden Hepatitis C, zurzeit mit pegyliertem Interferon α und Ribaverin. Glukokortikoide und Cyclophosphamid werden bei lebens- oder organbedrohenden Manifestationen eingesetzt (große Hautulzera, motorische Polyneuropathie, rapid-progressives Nierenversagen), können aber die Viruselimination verzögern und bilden bei den nicht virusvermittelten Kryoglobulinämien die Primärtherapie. B-Zell-depletierende Substanzen (Rituximab) haben hervorragende Ergebnisse sowohl bei der Hepatitis-C-assoziierten als auch bei der essenziellen kryoglobulinämischen Vaskulitis erbracht, mit Nachweis der Überlegenheit gegenüber Steroiden plus weiterer Immunsuppressiva. Seit dem Einsatz von Rituximab beschränkt sich der Einsatz der Plasmapherese auf Patienten mit Hyperviskosität durch Kryoglobuline. Abstract Cryoglobulinemic vasculitis consists of a group of immune complex-mediated diseases of small and medium-sized vessels, which mainly occur in association with hepatitis C infections or connective tissue diseases. Typical symptoms include purpuric skin changes, arthralgia and polyneuropathy often in conjunction with membranoproliferative glomerulonephritis. Classification criteria have recently been established which encompass serological and clinical parameters after detection of cryoglobulins in serum. Therapy is based on treatment of the underlying primary disease, e.g. antiviral treatment of hepatitis C with pegylated interferon-alpha and ribavirin. Corticosteroids and cyclophosphamide are administered for life or organ function threatening manifestations (e.g. large skin ulcers, severe motor neuropathy, rapid progressive glomerulonephritis), however they can slow down virus elimination and thus constitute the primary treatment in cases of non-virus-associated cryoglobulinemia. The B-cell depleting drugs (e.g. rituximab) have proven very effective for hepatitis C-associated as well as essential cryoglobulinemia and have shown to be superior to steroids plus additional immunosuppressants. Since the introduction of rituximab plasma exchange is only used in cases with hyperviscosity due to cryoglobulins.
    Der Nephrologe 05/2012; 7(3):209-221. DOI:10.1007/s11560-011-0607-6
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    ABSTRACT: The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
    Annals of the rheumatic diseases 11/2011; 71(6):955-60. DOI:10.1136/annrheumdis-2011-200477 · 10.38 Impact Factor
  • U. Erdbrügger · K. de Groot ·

    Zeitschrift für Rheumatologie 09/2011; 70(7):549-552. DOI:10.1007/s00393-011-0830-6 · 0.61 Impact Factor
  • U Erdbrügger · K de Groot ·
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    ABSTRACT: Methotrexate (MTX) in low-doses is an important component of anti-inflammatory therapy of rheumatoid arthritis and other inflammatory joint diseases. In contrast to high-dose administration of MTX in oncology, which can lead to direct tubulus toxicity and subsequent renal failure, renal side-effects are a rare exception for low-dose MTX. The biggest problem under low-dose MTX is that an already limited renal function due to comorbidities or an increasing, sometimes clinically insufficiently monitored renal insufficiency due to comedications, such as non-steroidal antirheumatics (NSAR) and antibiotics, leads to a reduced excretion of MTX and therefore to an accumulation in serum. This is primarily accompanied by gastrointestinal mucositis and bone marrow depression. For this reason low-dose MTX should never be administered once the glomerular filtration rate (GFR) is less than <30 ml/min and only 50% of the original dosage should be administered if the GFR is between 30 and 60 ml/min.
    Zeitschrift für Rheumatologie 07/2011; 70(7):549-52. · 0.61 Impact Factor
  • K de Groot · E Märker-Hermann ·
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    ABSTRACT: Patients with inflammatory rheumatic diseases often suffer from considerable comorbidities that can arise due to the chronic systemic inflammatory activity of the rheumatic disease itself, disorders of immune defense, or as a result of antirheumatic treatment; they can also occur independently. For example, almost 50% of patients with rheumatoid arthritis already exhibit two further chronic diseases at the time of initial manifestation. With regard to the elevated mortality observed in patients with rheumatism, particularly cardiovascular morbidity and increased predisposition to infections are of note. In addition, this article addresses further important possible concomitant diseases, i.e., osteoporosis and tumor diseases. A ground rule is to identify comorbidities and treat them just as diligently as the underlying rheumatic disease so that the patient with rheumatism should be accompanied by an interdisciplinary team of internists during each phase of the disease. Effective control of the systemic inflammatory activity may serve to reduce the risk of certain cardiovascular and neoplastic comorbidities.
    Der Internist 06/2011; 52(6):688-96. · 0.31 Impact Factor
  • K. de Groot · E. Märker-Hermann ·
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    ABSTRACT: Patienten mit entzündlich-rheumatischen Erkrankungen leiden häufig an relevanten Komorbiditäten, die durch die chronisch-entzündliche Systemaktivität der rheumatischen Krankheit selbst, durch Störungen der immunologischen Abwehr oder durch Folgen der antirheumatischen Therapie bedingt sein können, aber auch unabhängig davon auftreten können. So weisen zum Beispiel Patienten mit rheumatoider Arthritis bereits zum Zeitpunkt der Erstmanifestation in knapp 50% der Fälle 2 weitere chronische Krankheiten auf. Hinsichtlich der bei Rheumapatienten erhöhten Mortalität sind v.a. die kardiovaskuläre Morbidität und die erhöhte Disposition für Infektionen zu nennen. In diesem Artikel sollen zudem weitere wichtige mögliche Begleiterkrankungen, nämlich die Osteoporose und Tumorerkrankungen, behandelt werden. Es gilt, Komorbiditäten zu erkennen und ebenso konsequent zu behandeln wie die rheumatische Grunderkrankung, somit den an Rheuma erkrankten Patienten in jeder Krankheitsphase interdisziplinär internistisch zu begleiten. Eine effektive Beherrschung der systemischen Entzündungsaktivität vermag das Risiko bestimmter kardiovaskulärer und neoplastischer Komorbiditäten zu reduzieren. Patients with inflammatory rheumatic diseases often suffer from considerable comorbidities that can arise due to the chronic systemic inflammatory activity of the rheumatic disease itself, disorders of immune defense, or as a result of antirheumatic treatment; they can also occur independently. For example, almost 50% of patients with rheumatoid arthritis already exhibit two further chronic diseases at the time of initial manifestation. With regard to the elevated mortality observed in patients with rheumatism, particularly cardiovascular morbidity and increased predisposition to infections are of note. In addition, this article addresses further important possible concomitant diseases, i.e., osteoporosis and tumor diseases. A ground rule is to identify comorbidities and treat them just as diligently as the underlying rheumatic disease so that the patient with rheumatism should be accompanied by an interdisciplinary team of internists during each phase of the disease. Effective control of the systemic inflammatory activity may serve to reduce the risk of certain cardiovascular and neoplastic comorbidities. SchlüsselwörterEntzündliche Autoimmunerkrankung–Kardiovaskuläre Komorbidität–Neoplastische Komorbidität–Osteoporose–Infektion KeywordsInflammatory autoimmune disease–Cardiovascular comorbidity–Neoplastic comorbidity–Osteoporosis–Infection
    Der Internist 06/2011; 52(6):688-696. DOI:10.1007/s00108-010-2769-0 · 0.31 Impact Factor
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    ABSTRACT: Atherosclerosis is an inflammatory process mediated by circulating immune cells, including monocytes. There is accumulating evidence for the involvement of Toll-like receptor 4 (TLR-4) as a mediator of atherogenesis. We evaluated the association between CD14+/TLR-4+ monocytes in peripheral blood (flow cytometry) and future cardiovascular events (CVE), e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aortocoronary bypass, stroke and angiographically verified stenosis of peripheral arteries and cardiovascular (CV) death, in 191 patients with chronic kidney disease Stage V receiving hemodialysis therapy. At baseline, CD14+/TLR-4+ monocytes correlated significantly with age (r = 0.2; P = 0.007), high-sensitivity C-reactive protein (r = 0.2; P = 0.008) and mean arterial pressure (r = -0.2; P = 0.02), but not with gender (P = 0.5), smoking (P = 0.6) and the presence of diabetes (P = 0.5). During a median follow-up period of 36 [1-54] months, 79 (41%) patients experienced a CVE. A total of 55 patients died during the follow-up period, 25 of those due to a confirmed CV cause. Log-rank test did not reveal statistical significance for TLR-4+ monocytes concerning incident CVE (P = 0.3), CV death (P = 0.85) and overall death (P = 0.8). In a multiple Cox-regression analysis, we identified age (P = 0.003) and smoking (P = 0.001) as the only independent variables associated with incident CVE. Unexpectedly, we could not detect an association between CD14+/TLR-4+ monocytes and incident CVE as well as CV death in stable hemodialysis patients. Further studies have to clarify the potential role of this cell population for CV outcome in this population.
    Nephrology Dialysis Transplantation 04/2011; 26(4):1421-4. DOI:10.1093/ndt/gfq758 · 3.58 Impact Factor
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    ABSTRACT: Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease. Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models. The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival. Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
    Annals of the rheumatic diseases 03/2011; 70(3):488-94. DOI:10.1136/ard.2010.137778 · 10.38 Impact Factor
  • Ulf Schönermarck · Kirsten de Groot ·
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    ABSTRACT: Available evidence suggests that rituximab may be safe and effective for the treatment of refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Two studies now show that rituximab is not less effective than cyclophosphamide for treating ANCA-associated vasculitides. Should rituximab be the new standard of care for patients with ANCA-associated vasculitis?
    Nature Reviews Nephrology 01/2011; 7(1):6-8. DOI:10.1038/nrneph.2010.167 · 8.54 Impact Factor
  • U. Erdbrügger · K. Groot ·
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    ABSTRACT: Methotrexat (MTX) in ,,Low-dose“-Applikation ist eine wichtige Säule der antientzündlichen Therapie der rheumatoiden Arthritis und anderer entzündlicher Gelenkerkrankungen. Im Gegensatz zur ,,High-dose“-Anwendung von MTX in der Onkologie, das zur direkten Tubulustoxizität und zum konsekutiven Nierenversagen führen kann, sind renale Nebenwirkungen bei Low-dose-MTX eine seltene Ausnahme. Das größere Problem unter Low-dose-MTX liegt darin, dass eine a priori eingeschränkte Nierenfunktion durch Komorbiditäten oder eine zunehmende, manchmal klinisch nichtausreichend beachtete Niereninsuffizienz im Rahmen einer Komedikation mit z. B. nichtsteroidalen Antirheumatika (NSAR), Antibiotika etc. zu einer verminderten MTX-Ausscheidung und damit Kumulation der Substanz im Serum führt. Dies geht in erster Linie mit gastrointestinaler Mukositis und Knochenmarkdepression einher. Aus diesem Grund sollte auch Low-dose-MTX bei einer glomerulären Filtrationsrate (GFR) Keywords: Arzneimittelwechselwirkung; Dose-response relationship; Dosis-Wirkung-Verhältnis; Drug interactions; Glomerular filtration rate; Glomeruläre Filtrationsrate; Hematuria; Hämaturie; Proteinuria; Proteinurie Document Type: News DOI: Affiliations: 1: Division of Nephrology, University of Virginia Health System, 800133, 22908, Charlottesville, USA, Email: 2: Medizinische Klinik III (Nephrologie, Hypertensiologie, Rheumatologie), KfH Nierenzentrum Offenbach, Klinikum Offenbach GmbH, Starkenburgring 66–70, 63069, Offenbach, Deutschland, Email: Publication date: September 1, 2011 $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher By this author: Erdbrügger, U. ; Groot, K. GA_googleFillSlot("Horizontal_banner_bottom");
    Zeitschrift für Rheumatologie 01/2011; 70(7). · 0.61 Impact Factor
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    ABSTRACT: Current remission maintenance therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are limited by partial efficacy and toxicity. To compare the effects of mycophenolate mofetil with azathioprine on the prevention of relapses in patients with AAV. Open-label randomized controlled trial, International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE), to test the hypothesis that mycophenolate mofetil is more effective than azathioprine for preventing relapses in AAV. The trial was conducted at 42 centers in 11 European countries between April 2002 and January 2009 (42-month study). Eligible patients had newly diagnosed AAV (Wegener granulomatosis or microscopic polyangiitis) and were aged 18 to 75 years at diagnosis. Patients were randomly assigned to azathioprine (starting at 2 mg/kg/d) or mycophenolate mofetil (starting at 2000 mg/d) after induction of remission with cyclophosphamide and prednisolone. The primary end point was relapse-free survival, which was assessed using a Cox proportional hazards model. The secondary end points were Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria. A total of 156 patients were assigned to azathioprine (n = 80) or mycophenolate mofetil (n = 76) and were followed up for a median of 39 months (interquartile range, 0.66-53.6 months). All patients were retained in the analysis by intention to treat. Relapses were more common in the mycophenolate mofetil group (42/76 patients) compared with the azathioprine group (30/80 patients), with an unadjusted hazard ratio (HR) for mycophenolate mofetil of 1.69 (95% confidence interval [CI], 1.06-2.70; P = .03). Severe adverse events did not differ significantly between groups. There were 22 severe adverse events in 13 patients (16%) in the azathioprine group and there were 8 severe adverse events in 8 patients (7.5%) in the mycophenolate mofetil group (HR, 0.53 [95% CI, 0.23-1.18]; P = .12). The secondary outcomes of Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria did not differ significantly between groups. Among patients with AAV, mycophenolate mofetil was less effective than azathioprine for maintaining disease remission. Both treatments had similar adverse event rates. Identifier: NCT00307645.
    JAMA The Journal of the American Medical Association 11/2010; 304(21):2381-8. DOI:10.1001/jama.2010.1658 · 35.29 Impact Factor
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    ABSTRACT: Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function. We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort. In our patients EPCs were related only to age (r=0.154; p=0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p=0.03) and patient age (p=0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p=0.02). We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population.
    PLoS ONE 07/2010; 5(7):e11477. DOI:10.1371/journal.pone.0011477 · 3.23 Impact Factor
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    ABSTRACT: The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis. The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce 'points to consider' in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used. There was unanimous consensus for re-evaluating existing definitions and developing new criteria. A total of 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of anti-neutrophil cytoplasm antibody and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasising its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered. Limitations in current classification criteria and definitions for vasculitis have been identified and suggestions provided for improvement. Additionally it is proposed that, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.
    Annals of the rheumatic diseases 05/2010; 69(10):1744-50. DOI:10.1136/ard.2009.119032 · 10.38 Impact Factor

Publication Stats

6k Citations
599.22 Total Impact Points


  • 2011
    • University of Virginia
      Charlottesville, Virginia, United States
  • 2007-2011
    • Klinikum Offenbach GmbH
      Frankfurt, Hesse, Germany
  • 2001-2011
    • Hannover Medical School
      • Institute for Pathology
      Hanover, Lower Saxony, Germany
  • 2008
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2004
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2000-2001
    • Universität zu Lübeck
      • Poliklinik für Rheumatologie
      Lübeck Hansestadt, Schleswig-Holstein, Germany