B Grabensee

Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (458)1003.78 Total impact

  • W. Kleophas · B. Grabensee
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    ABSTRACT: Eine exakte Diagnostik mit unterschiedlichen Methoden von der Anamnese und dem klinischen Bild bis hin zu differenzierten apparativen, molekularbiologischen und -genetischen Methoden ist bei Nieren- und Hochdruckkrankheiten sowohl zu Beginn der Erkrankung als auch im Verlauf unerlässlich. Neben der Entscheidung für eine differenzierte Therapie rückt die Aussage zur Prognose von Nierenerkrankungen und zur Beteiligung der Nieren bei Systemerkrankungen unter dem Gesichtspunkt der Prävention immer mehr in den Vordergrund. Im vorliegenden Heft werden von kompetenten Autoren aktuelle diagnostische Möglichkeiten bei Nieren- und Hochdruckkrankheiten dargestellt. O. Vonend und Koautoren geben vor dem Hintergrund neuer, zum Teil eingreifender Therapiemaßnahmen einen aktuellen Überblick über das praktische Vorgehen bei der Differenzialdiagnostik der schwer einstellbaren Hypertonie. Neben der ausführlichen Darstellung des praktischen Vorgehens zum Ausschluss bzw. zur Diagnostik einer sekundären Hy ...
    No preview · Article · Sep 2012 · Der Nephrologe
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    ABSTRACT: Plasma-ANP- (pg/ml; Radioimmunassay) als Parameter einer postischämischen Dysfunktion und Troponin-T-Spiegel (TnT) (ng/ml; ELISA) als Indikator eines ischämischen Zellschadens wurden vor, während und nach der extrakorporalen Zirkulation (EKZ) bei 15 Patienten mit koronarer Herzerkrankung (KHK) (mittleres Alter: 58±6,1 Jahre; 13m, 2w; alle ohne eingeschränkte linksventrikuläre Funktion und Zeichen einer kongestiven Herzerkrankung) untersucht. Unter standardisierten Bedingungen bei der EKZ wurden Basisdaten bezüglich der kardialen Hämodynamik (Herzfrequenz (HF); systolischer (RR sys,mmHg), diastolischer Druck (RR dia,mmHg); zentralvenöser Druck (ZVD,mmHg); linksatrialer Druck (LAP,mmHg); linksventrikulärer, enddiastolischer Druck (LVEDP,mmHg)) dokumentiert und unter Elektrokardiographie (EKG) – Monitoring wurden Blutproben entnommen: 1) 10 min vor Anästhesiebeginn; 2) vor EKZ; 3) nach 1h EKZ; 4) 5min nach EKZ-Ende; 5) 1h nach EKZ-Ende; 6) 6h postoperativ (postop); 7) 24h postop; 8) 48h postop; 9) 10 Tage postop. Zusätzlich wurden mit Hilfe der ¶M-Mode Echokardiographie (Echo) prä- und am 10. postoperativen Tag der linksatriale Durchmesser (LAD, mm), der linksventrikuläre enddiastolische Durchmesser bei Q (LVEDD, mm) gemessen und die Ejektionsfraktion (EF, %) berechnet.¶   Die Bestimmung der ANP- bzw. TnT-Konzentrationen im Plasma des arteriellen und venösen Blutes erfolgte mittels eines Doppel-Antikörpers (AK)-Radioimmunoassay bzw. ELISA-Tests.¶   Bei dem Kollektiv der KHK-Patienten fand sich ein Konzentrationsanstieg des ANPs von 90±10 (M±SEM)pg/ml (p<0,05) auf intraoperativ 380±38pg/ml. Noch am 10. postoperativen Tag, lag der ANP-Spiegel mit 262±33pg/ml (p<0,05) auf einem 3fach höherem Niveau als die Ausgangswerte. Das TnT zeigte ebenfalls einen Anstieg von präoperativ 0,02±0,01ng/ml auf intraoperativ 3,44±0,47ng/ml (p<0,05). Am 10. postop Tag lag die TnT-Konzentration mit 0,13±0,11ng/ml in Höhe des präoperativen Ausgansniveaus. 5 min nach Bypassende und bis zu 6 h postop korrelierten die ANP- und TnT-Werte bei p<0,05 mit einem r von 0,41. Der mittels der M-Mode Echo ermittelte LAD erhöhte sich von präoperativ 42,2±1,1 mm auf 46,8±1,2 mm (p<0,05) am 10. postop Tag. LVEDD und EF betrugen präoperativ 51,1±0,9 mm bzw. 73±2% und lagen am 10. postop Tag bei 54,5±1,2 mm bzw. 65±4% (p<0,05).¶   Die signifikant erhöhten TnT-Spiegel zeigen einen durch die Operation verursachten, zellulären Myokardschaden an, der sich nicht in EKG-Veränderungen niederschlägt, jedoch ein echokardiographisch erfassbares Korrelat einer kardialen Dysfunktion aufzeigt. Die signifikant (p<0,05) bis zum 10. postop Tag erhöhten ANP-Spiegel können sehr sensitiv das Vorliegen einer möglichen prolongierten, postischämischen Dysfunktion nach unkomplizierter Bypasschirurgie widerspiegeln, die bis zum 10. postop Tag noch nicht kompensiert ist. Plasma levels of ANP (pg/ml; radioimmunassay) as a parameter for postischemic dysfunction and levels of Troponin T (TnT) (ng/ml; ELISA test) as a parameter for postischemic cellular damage were determined in 15 patients with coronary artery disease (CAD) (mean age: 58±6.1 years; 13m, 2w; with no history of myocardial infarction and no signs for congestive heart failure) prior to, during and after extracorporal circulation (ECC).¶   Under standardized conditions during the ECC basic parameters concerning the cardial hemodynamic (heart rate (HR); systolic (RRsys,mmHg), diastolic pressure (RR dia,mmHg) central venous pressure (CVP,mmHg); left atrial pressure (LAP,mmHg); left ventricular enddiastolic pressure (LVEDP,mmHg)) and ECG monitoring blood samples were performed: 1) prior to operation (op); 2) prior to CPB; 3) 1 h CPB; 4) 5 min after CPB; 5) 1 h after CPB; 6) 6 h postoperative (postop); 7) 24 h postop; 8) 48 h postop; 9) 10 days postop. Also the left atrial diameter (LAD, mm) and the left ventricular enddiastolic diameter at Q (LVEDD, mm) pre- and postop were documented with¶m-mode echocardiography (Echo) and ejection fraction (EF, %) was calculated.¶   The bypass operations were performed with intermittent aortic crossclamping with open venae cavae (CVP: 0–5mmHg) and moderate hypothermia.¶   For the determination of ANP levels and TnT levels in atereal and venous blood, a double-antibody (AB) radioimmunassay and an ELISA test were used.¶   Concerning the patients with CAD there was a maximal increase of ANP from preoperative 90±10 (M±SEM)pg/ml ( p<0.05) up to intraoperative 380±38pg/ml. Ten days postop, the ANP level was with 262±33pg/ml still increased threefold in comparison to the preoperative level. TnT showed an increase from preoperative 0.02±0.01ng/ml up to intraoperative 3.44±0.47ng/ml. Ten days postop the TnT concentration was at the preoperative level with 0.13±0.11ng/ml. Five minutes after bypass up to 48 h postop, ANP and TnT levels were correlated (p<0.05, r=3.4). There was an increase of the LAD from preoperative 42.2±1.1 mm up to 46.8±1.2 mm (p<0.05) 10 days postop as determined by m-mode echo. LVEDD and EF changed from preoperative 51.1±0.9 mm and 73±2% to 54.5±1.2 mm and 65±4% 10 days postop.¶   The significant increase of TnT (172-fold) indicates the cellular, myocardial injury, caused by the operation without signs in ECG recordings and no signs of congestive heart failure. The significantly increased ANP level up to the 10th day postop indicate sa very sensitive prolonged, postischemic dysfunction, which is not compensated 10 days postop. Schlüsselwörter ANP – Troponin – koronare Herzerkrankung – myokardiale Verletzungen – postischämische DysfunktionKey words ANP – troponin – coronary artery disease – myocardial injury – postischemic dysfunction
    Full-text · Article · Apr 2012 · Zeitschrift für Kardiologie
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    ABSTRACT: Background After renal transplantation, patients are prone to develop impairments in glucose metabolism. In 2005, the American Diabetes Association published new guidelines on the diagnosis of pre-diabetes [plasma glucose levels from 100 to 125 mg/dL fasting or from 140 to 199 mg/dL 2 h after an oral glucose tolerance test (OGTT)]. This study sought to evaluate the prevalence and the potentially associated factors of pre-diabetes in a cohort of renal transplant patients on maintenance immunosuppressive medication. Furthermore, the diagnostic value of HbA1-c measurements in predicting pre-diabetes in transplant patients is undetermined.
    Full-text · Article · Apr 2012 · Nephrology Dialysis Transplantation
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    ABSTRACT: Thrombotic microangiopathies (TMA) in adults such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are life-threatening disorders if untreated. Clinical presentation is highly variable and prognostic factors for clinical course and outcome are not well established. We performed a retrospective observational study of 62 patients with TMA, 22 males and 40 females aged 16 to 76 years, treated with plasma exchange at one center to identify clinical risk factors for the development of renal insufficiency. On admission, 39 of 62 patients (63%) had acute renal failure (ARF) with 32 patients (52%) requiring dialysis treatment. High systolic arterial pressure (SAP, p = 0.009) or mean arterial pressure (MAP, p = 0.027) on admission was associated with acute renal failure. Patients with SAP>140 mmHg on admission had a sevenfold increased risk of severe kidney disease (OR 7.464, CI 2.097-26.565). MAP>100 mmHg indicated a fourfold increased risk for acute renal failure (OR 4.261, CI 1.400-12.972). High SAP, diastolic arterial pressure (DAP), and MAP on admission were also independent risk factors for persistent renal insufficiency with the strongest correlation for high MAP. Moreover, a high C-reactive protein (CRP) level on admission correlated with renal failure in the course of the disease (p = 0.003). At discharge, renal function in 11 of 39 patients (28%) had fully recovered, 14 patients (23%) remained on dialysis, and 14 patients (23%) had non-dialysis-dependent chronic kidney disease. Seven patients (11%) died. We identified an older age as risk factor for death. High blood pressure as well as high CRP serum levels on admission are associated with renal insufficiency in TMA. High blood pressure on admission is also a strong predictor of sustained renal insufficiency. Thus, adult TMA patients with high blood pressure may require special attention to prevent persistent renal failure.
    Full-text · Article · Jan 2012 · PLoS ONE

  • No preview · Article · Nov 2011 · International journal of cardiology
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    ABSTRACT: Continuous venovenous haemofiltration (CVVH) in the intensive care setting requires anticoagulation to prevent clotting of the extracorporeal circuit. Several protocols avoiding heparin and using regional citrate anticoagulation have been developed to diminish bleeding risks. However, data from randomized trials comparing citrate anticoagulation with systemic heparinization are very limited. One hundred and seventy-four patients on mechanical ventilation, requiring renal replacement therapy for acute renal failure, were included in this prospective randomized multicentre trial comparing regional citrate with systemic heparin. The study was performed at nine different intensive care units at university or academic teaching hospitals. The participants were randomized to either CVVH using regional citrate anticoagulation or CVVH using systemic anticoagulation with unfractionated heparin. The primary outcome was to compare treatment efficacy represented by the patients' acid base status on Day 3 and on each consecutive day. Several parameters of safety and efficacy were analysed as secondary outcomes. Comparison of standard bicarbonate from Day 3 to Day 11 revealed no difference between both treatment modalities. Use of citrate resulted in less systemic anticoagulation, a lower risk of bleeding and a longer haemofilter patency. Episodes of hypercalcaemia, hypocalcaemia and the need for additional bicarbonate infusions occurred more often under citrate. The patients' high mortality was not influenced by the mode of anticoagulation. Citrate may be used as a regional anticoagulant and the only buffering agent in CVVH with adequate treatment efficacy and safety. However, neither citrate nor heparin anticoagulation should be regarded as a therapeutic standard, since there is no advantage of one of these substances with regard to patient mortality.
    Full-text · Article · Sep 2010 · Nephrology Dialysis Transplantation
  • W. Kleophas · B. Grabensee

    No preview · Article · Jan 2010 · Der Nephrologe
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    W. Kleophas · B. Grabensee

    Preview · Article · Jan 2010 · Der Nephrologe
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    ABSTRACT: Renin-angiotensin-aldosterone system (RAAS) polymorphisms such as the angiotensinogen-gene-M235T-, the angiotensin-conversion enzyme (ACE)-gene I/D- and the angiotensin-II-type 1-receptor-(AT1R)-A1166C-polymorphism have been implicated in renal insufficiency and hypertension. We studied the association of these RAAS genotypes and non-genetic factors with transplant function and hypertension after renal graft transplantation (NTX). A total of 229 renal graft recipients, transplanted at a single center, were monitored up to 54 months and genotyped using polymerase chain reaction. The prevalence of the genotypes was comparable to a control group of healthy volunteers. Genotype and clinical outcome was analyzed using ANOVA, while the k-nearest neighbor method was used for a pattern recognition analysis of the complete database. Hypertension after NTX was not influenced by the RAAS polymorphisms. The DD-genotype of the ACE-I/D-polymorphism was associated with significantly deteriorated renal transplant function during the months 18 to 30 after transplantation according to ANOVA at p < 0.05, as were non-genetic factors like long hospitalization, poor primary transplant function, and frequent rejections. Pattern recognition identified, the use of cyclosporine (odds ratio of 4.25) and the use of Ang II-receptor-blockers at discharge indicating the need of effective antihypertensive treatment (odds ratio of 3.26) as risk factors for transplant function loss. Altogether, the significant impact of the DD-genotype on the outcome after renal transplantation emphasizes the early identification of RAAS genotypes.
    Full-text · Article · Sep 2009 · Clinical Transplantation
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    ABSTRACT: In this study, we assessed the potential role of the TT genotype of the gene of the methylenetetrahydrofolate reductase for the manifestation of thrombotic microangiopathies, enrolling 40 affected patients (mean age [+/- standard deviation] 35 +/- 11 years). As a result, the methylenetetrahydrofolate reductase 677TT genotype was more prevalent in patients with thrombotic microangiopathies compared with controls (adjusted odds ratio = 2.58, 95% confidence interval = 1.2-5.7, P = .018), particularly in those suffering from the hemolytic uremic syndrome. A hemolytic more severe clinical course of thrombotic microangiopathies in carriers of the methylenetetrahydrofolate reductase 677TT genotype was not observed. In summary, our findings suggest a significant influence of the methylenetetrahydrofolate reductase genotype on the manifestation of thrombotic microangiopathies. The 677 TT genotype of this polymorphism appears to be a risk factor for manifestation of these rare thrombotic disorders, possibly explained by endothelial activation and increased oxidative stress.
    No preview · Article · Jul 2009 · Clinical and Applied Thrombosis/Hemostasis
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    ABSTRACT: Factor V Leiden (FVL) mutation and prothrombin G20210A mutation are common hereditary risk factors for venous thrombosis. In the current study, 40 patients (mean age +/- standard deviation, 35 +/- 11 years) and 764 healthy control subjects (mean age +/- standard deviation, 37 +/- 14 years) were enrolled to assess the potential role of these mutations in the manifestation of thrombotic microangiopathies. Compared with controls, neither the heterozygous FVL mutation (7.5% vs 8.5%; P = 1) nor the heterozygous prothrombin mutation (2.5% vs 2.8%; P = 1) was more prevalent in the patients. The findings do not support a significant role of FVL and prothrombin mutations as risk factors for the manifestation of thrombotic microangiopathies. Thus, screening for these mutations does not allow the identification of individuals at increased risk for these rare thrombotic disorders.
    No preview · Article · Jul 2009 · Clinical and Applied Thrombosis/Hemostasis
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    ABSTRACT: Inflammation is a well recognized central component of atherosclerotic processes in chronic kidney disease. Interleukin-6 (IL-6) levels are a strong determinant of cardiovascular mortality in dialysis patients. We evaluated the impact of IL-6 gene G-174C polymorphism associated with modified IL-6 production on the development of coronary artery disease (CAD), cardiovascular events and mortality in chronic dialysis patients. We studied n = 463 patients on chronic dialysis with angiographically confirmed (n = 218) or excluded (n = 245) CAD followed up for 65 months after initiation of dialysis. Monitored were arterial hypertension, diabetes mellitus, hyperlipidemia, smoking, CRP and fibrinogen. IL-6 gene G-174C polymorphism was determined by PCR amplification. The CC genotype was associated with an impaired patient survival (p < 0.05) remaining an independent risk factor for death in multivariate analysis (HR for CC genotype: 3.58, CI: 1.41-9.07, p < 0.01). CC genotype carrying CAD patients suffered significant frequently cardiovascular events (revascularization, myocardial infarction, death) compared to GG/GC genotype carriers (85.2% vs. 66.5, p < 0.05). However, the IL-6 gene G-174C polymorphism was not related to the onset and development of CAD itself (ns) and the inflammation parameters CRP and fibrinogen did not differ between the genotypes under investigation (ns). Our results suggest that IL-6 gene G-174C polymorphism is associated with the incidence of cardiovascular events and mortality in chronic dialysis patients.
    Preview · Article · Apr 2009 · Nephrology Dialysis Transplantation
  • A. Holstein · K. Ivens · B. Grabensee · U. Mödder · A. Scherer

    No preview · Article · Jan 2009 · Der Nephrologe
  • B. Grabensee · H. Haller

    No preview · Article · Jan 2009 · Der Nephrologe
  • A. Holstein · K. Ivens · B. Grabensee · U. Mödder · A. Scherer
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    ABSTRACT: Von der MDCT-Technik und ihrer mittlerweile weiten Verfügbarkeit hat auch die Bildgebung bei Nieren- und Hochdruckkrankheiten profitiert. In zunehmendem Maße kann die MDCT Indikationen der (invasiven) konventionellen Angiographie übernehmen und die i.v.-Urographie vollständig ersetzen. Zur Minimierung der Gesamtstrahlendosis ist für jede Fragestellung ein maßgeschneidertes Untersuchungsprotokoll anzuwenden. Soweit sinnvoll sollten Niedrigdosisprotokolle (z.B. zur Diagnostik der Urolithiasis) zur Anwendung kommen. Durch die Verbesserung der longitudinalen Auflösung (z-Achse) und der resultierenden isotropen Voxel stehen vielfältige Möglichkeiten der Bildrekonstruktion zur Verfügung. Die Anfertigung von multiplanaren Rekonstruktionen, dünneren Schichten und/oder 3D-Rekonstruktionen kann in vielen Fällen hilfreich bei der Diagnosefindung sein. Grundlage einer aussagekräftigen Untersuchung ist nicht zuletzt eine gute Kommunikation zwischen klinisch tätigen Ärzten und Radiologen. Imaging of renal and hypertonic diseases has also profited from multidetector computed tomography which is now widely available. MDCT is increasingly being used when there are indications for conventional (invasive) angiography and has completely supplanted i.v. urography. In order to minimize the total radiation dose a tailor-made investigation protocol must be applied in every situation. As far as this makes sense low-dose protocols (e.g. for the diagnosis of urolithiasis) should be applied. Improvement of the longitudinal resolution (z-axis) and the resulting isotropic voxels means that many options for image reconstruction are now available. The production of multiplanar reconstructions, thinner slice or 3-D reconstruction can greatly assist the diagnosis in many cases. The fundament of a conclusive examination is also a good communication between clinical physicians and radiologists.
    No preview · Article · Dec 2008 · Der Nephrologe
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    B. Grabensee · H. Haller

    Preview · Article · Dec 2008 · Der Nephrologe
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    ABSTRACT: The G-1082A polymorphism of the interleukin-10 (IL-10) gene has been associated with modified gene expression and the progression of primary IgA nephropathy (IgAN). In the present study, we evaluated its influence on recurrent IgAN after renal transplantation. We studied 103 patients who suffered from IgAN and underwent renal transplantation, followed up for 5.8 -/+ 3.4 years. A cohort of 206 matched renal allograft recipients with other primary diseases was analyzed as a control group. IL-10 gene G-1082A polymorphism was determined by PCR amplification. Microscopic hematuria and/or proteinuria of more than 500 mg/24 hours occurred in 22 patients (21%). Histological confirmation of IgAN recurrence was obtained in 16 patients. Young recipient age was associated with biopsy-proven IgAN recurrence in the Kaplan-Meier analysis of recurrence-free survival (p=0.05). The presence of IgAN recurrence had no impact on graft survival (not significant [NS]). Furthermore, graft survival was similar in patients with IgAN and patients with other primary diseases (NS). The IL-10 GG genotype was associated with a higher recurrence rate in the Kaplan-Meier analysis of recurrence-free survival (p<0.05). IgAN recurrence is a common complication, especially in younger renal transplant recipients. IL-10 gene G-1082A polymorphism was associated with an increased recurrence rate.
    No preview · Article · Nov 2008 · Journal of nephrology
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    ABSTRACT: A number of medical, mostly immune-mediated conditions call for a combination therapy consisting of plasmapheresis and haemodialysis. While the two treatments are most commonly applied separately, we describe here the technical details of providing a combined 'tandem' treatment. Method. The components of a dialyzer (polysulfon membrane) and plasma filter are serially connected by a continuous arteriovenous haemofiltration (CAVH) system. In an extracorporeal circulation, using a blood pump the patient's blood is led first to the plasma filter and then into the dialyzer. The substituate connection is located behind the plasma filter and before the dialyzer. At the beginning it is obligatory to carry out an inspection of tubing system leakages. Afterwards, the system is flushed with a heparinized (5000 IE) sodium chloride solution that is removed thereafter. During the treatment, a blood flow of 150-200 ml/min is possible. In each case, the plasmafiltration and the ultrafiltration should not exceed 25% of the blood flow. The whole time, an intermittent check of blood pressure and heart rate is necessary. The total procedure does not take longer than a routine haemodialysis (3-4 h). In 82 patients we performed 483 tandem treatments during the last 16 years. None of the patients had volume disturbances caused by plasma shifts and derangements of electrolytes and acid-base balance were immediately equalized. There were no episodes of hypotension or bleeding. Back-filtration did not occur. Providing both haemodialysis and plasmapheresis at the same time reduces treatment time and thus, overall cost of the treatment. This retrospective analysis shows the tandem treatment to be safe and effective.
    Full-text · Article · Sep 2008 · Nephrology Dialysis Transplantation
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    ABSTRACT: Uncontrolled mesangial cell (MC) proliferation within the context of glomerular disease contributes to the development of glomerulosclerosis. Mesangial autocrine growth factor stimulation has been described as a pathogenic factor. We investigated the effects of mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil (MMF), on proliferation factors of cultured rat MCs. MPA was tested on the expression of platelet-derived growth factor-B (PDGF-B) and its receptor beta (PDGFR-beta), the immediate early gene (IEG) c-fos and the early growth response gene-1 (Egr-1), and AP-1 activation. Growth-arrested rat MCs were stimulated with 10% fetal calf serum (FCS) or 10-25 ng/ml platelet-derived growth factor-BB (PDGF-BB) in the presence or absence of MPA (0.019-10 microM) with or without guanosine (100 microM). MC proliferation was quantified by 5-bromo-2'-deoxyuridine (BrdU) incorporation and direct cell counting. Cytotoxicity of MPA was evaluated using the MTT and LDH tests. Protein expression of PDGF-B and its receptor PDGFR-beta was quantified by western blot analysis. The effect of MPA on gene expression of PDGF-B, Egr-1 and c-fos was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR). AP-1 activation was analysed by an electrophoretic mobility shift assay (EMSA). Exposure of MCs to MPA caused a concentration-dependent inhibition of FCS-induced cell proliferation (cell number increase) with an IC50 of 0.44 +/- 0.03 microM and DNA synthesis with an IC50 of 0.52 +/- 0.02 microM without cell cytotoxicity in the therapeutic range. MPA decreased the PDGF-B protein expression and mRNA self-induction of PDGF-B but did not alter the protein expression of PDGFR-beta. MPA strongly inhibited the PDGF-BB-induced mRNA expression of Egr-1 decreasing to 7.6 +/- 2.5% after 30 min (P <or= 0.001) and to 4.7 +/- 3.1% after 1 h (P <or= 0.05), both being compared to the maximal expression induced by PDGF-BB. PDGF-BB-induced c-fos expression under MPA was unchanged after 30 min and decreased to 57 +/- 26% after 1 h (n.s.). MPA treatment did not affect PDGF-BB-induced AP-1 activity determined after 1 h and 2 h. The inhibitory MPA effect on PDGF-BB-induced PDGF-B expression was not significantly restored by guanosine (56 +/- 18% versus 32 +/- 17% after 2 h, n.s.), and MPA inhibition of PDGF-BB-induced Egr-1 expression was not reversed by exogenous guanosine. Treatment of cultured MCs with MPA inhibits MC proliferation correlating with a downregulation of the PDGF-B gene and protein expression and a suppression of Egr-1 mRNA expression. Since exogenous guanosine was not able to reverse the inhibitory MPA effect on PDGF-B and Egr-1 expression, we conclude that the antiproliferative effect of MPA on MCs may not solely depend on dGTP depletion but on a specific interference with the autocrine PDGF-B synthesis and Egr-1 expression of MCs.
    Full-text · Article · Sep 2008 · Nephrology Dialysis Transplantation
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    ABSTRACT: Switching from cyclosporine to tacrolimus without steroid pulse was suggested as a therapeutic option in chronic allograft nephropathy (CAN). Thirty-one renal transplant recipients with CAN were prospectively converted from cyclosporine to tacrolimus (group A), in parallel 31 matched cyclosporin A (CsA) patients (group B) without CAN were followed up for 30 months. In six matching patients of groups A and B inulin and para-aminohippurate (PAH)-clearances and mycophenolate were measured over a span of 3 months. Transplant biopsies of group A were scored according to BANFF. While group A presented with transplant dysfunction compared with group B before switching (2.7 +/- 0.16 mg/dl vs. 1.7 +/- 0.09 mg/dl; P < 0.001), transplant function was equal 30 months later: it ameliorated in group A (2.0 +/- 0.18 mg/dl vs. 2.7 +/- 0.16 mg/dl; P < 0.001) and decreased in group B (1.9 +/- 0.13 mg/dl vs. 1.7 +/- 0.09 mg/dl, P < 0.05). Especially, patients with biopsy scores I and II according to BANFF benefited from tacrolimus. Within 3 months, mycophenolate acid (MPA) levels increased under tacrolimus (P < 0.05) whereas inulin and PAH-clearances remained unchanged. At switching, antihypertensive treatment was more intense in group B, but this difference evened out. Adverse side effects were more frequent under tacrolimus. Patients with mild to moderate CAN significantly benefited from switching to tacrolimus. Increased MPA-levels under tacrolimus might have contributed to this effect.
    Full-text · Article · Sep 2008 · Transplant International

Publication Stats

5k Citations
1,003.78 Total Impact Points

Institutions

  • 1974-2012
    • Heinrich-Heine-Universität Düsseldorf
      • • Faculty of Medicine
      • • Klinik für Nephrologie
      • • Nuklearmedizinische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1982-2008
    • Universitätsklinikum Düsseldorf
      • Neurologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1999
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
    • Ghent University
      • Department of Internal Medicine
      Gand, Flanders, Belgium
  • 1998
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden