Lutz T. Weber

University Hospital Cologne

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Burkhard Tönshoff

Heidelberg University

Jun Oh

University Medical Center Hamburg-Eppendorf

Marcus R. Benz

Helios Amper-Klinikum Dachau

Rasmus Ehren

University of Cologne

Lars Pape

Medizinische Hochschule Hannover

Sandra Habbig

University Hospital Cologne

Max C. Liebau

University Hospital Cologne

Dieter Haffner

Medizinische Hochschule Hannover

Jörg Dötsch

Klinik und Poliklinik für Kinder- und Jugendmedizin

Franz Schaefer

University Hospital Heidelberg

Cooperative Institutions

University Hospital Cologne

230

University of Cologne

226

Heidelberg University

223

University Hospital Heidelberg

180

RELX Group (United States)

140

Boston Children's Hospital

135

Medizinische Hochschule Hannover

135

Klinik und Poliklinik für Kinder- und Jugendmedizin

132

University of Toronto

125

Charité - Universitätsmedizin Berlin

114

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Comparison of the Emit Immunoassay with HPLC for Therapeutic Drug Monitoring of Mycophenolic Acid in Pediatric Renal-Transplant Recipients on Mycophenolate Mofetil Therapy

Clinical Chemistry (2002)

Lutz T. Weber Maria Shipkova Victor W. Armstrong Natalie Wagner Ekkehard Schütz

HPLC is currently the preferred method for accurate measurement of mycophenolic acid (MPA). This study was designed to validate the Emit compared with HPLC in relation to clinical outcome measurements.Pediatric renal-transplant recipients (n = 50) on an immunosuppressive triple regimen consisting of cyclosporin A, prednisone, and mycophenolate mofetil (600 mg/m(2) twice per day) were investigated in an open-label prospective study. Pharmacokinetic profiles over 12 h were obtained at 1 week, 3 weeks, 3 months, and 6 months posttransplant. Plasma MPA was measured by both reversed-phase HPLC and the Emit immunoassay.There was an association between the risk of acute rejection episodes and low area under the curve values from t(0) to t(12h) (AUC(0-12)) for MPA (MPA-AUC(0-12)) or predose concentrations of MPA derived from both HPLC and Emit measurements. According to ROC analysis, an AUC value of 33.8 mg x h/L for MPA from t(0) to t(12h) (MPA-AUC(0-12)) determined by HPLC had a diagnostic sensitivity of 80% and a diagnostic specificity of 57%. The corresponding value of the Emit was 36.1 mg x h/L. For the predose concentration (MPA-c(12)), a concentration of 1.2 mg/L determined by HPLC and 1.4 mg/L determined by Emit gave a sensitivity of 80% and a specificity of 60%, respectively. There was no association of any pharmacokinetic variables derived from total MPA measurements with an increased risk of side effects related to mycophenolate mofetil.The Emit assay appears to have a comparable diagnostic efficacy to HPLC for assessing the risk of acute rejection in pediatric renal-transplant recipients. However, because of the cross-reactivity of the antibody used in the Emit assay with the active MPA acyl glucuronide metabolite, the decision thresholds for the Emit were higher than those calculated from HPLC measurements.

Mycophenolate

Therapeutic Drug Monitoring

10.1093/clinchem/48.3.517

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Citations (121)

Novel heterozygous COL4A3 mutation in a family with late-onset ESRD

Pediatric Nephrology (2010)

Julia Hoefele Bärbel Lange-Sperandio Despina Ruessmann Judith Glöckner-Pagel Martin Alberer

Alport syndrome

Nephrology

10.1007/s00467-010-1467-4

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Citations (18)

Limitations of dual x-ray absorptiometry in children with chronic kidney disease

Pediatric Nephrology (2009)

Lutz T. Weber Otto Mehls

Nephrology

Densitometry

Dual-Energy X-ray Absorptiometry

10.1007/s00467-009-1248-0

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Citations (39)

RAGE-mediated interstitial fibrosis in neonatal obstructive nephropathy is independent of NF-κB activation

Kidney International (2013)

Mojca Gasparitsch Anne-Karin Arndt Felix Pawlitschek Stephan Oberle U Keller

Urinary tract obstruction during nephron development causes tubular apoptosis, tubular atrophy, and interstitial fibrosis. Leukocyte recruitment is critical in the development of obstructive nephropathy leading to interstitial inflammation and renal fibrosis. RAGE, the receptor of advanced glycation end products, is implicated in chronic inflammation and has been recently identified as a novel receptor for the β2-integrin Mac-1, cooperating with ICAM-1 and thereby directly mediating leukocyte recruitment in vivo. Here, we studied the role of RAGE and ICAM-1 in a model of unilateral ureteral obstruction in neonatal mice. Interestingly, the number of infiltrating leukocytes was independent of RAGE and ICAM-1 in the ureteral obstructed neonatal kidney. By contrast, galectin-3, a marker for profibrogenic M2 macrophages, was strongly reduced in ureteral obstructed RAGE and RAGE-Icam1 knockout mice. Snail expression and loss of E-cadherin but not NF-κB activation were attenuated in both knockout models. Epithelial cell cycle arrest at G2/M, which mediates kidney fibrosis, and transforming growth factor-β expression were reduced in ureteral obstructed RAGE knockout mice. Thus, RAGE and ICAM-1 promote renal fibrosis in the developing kidney upon ureteral obstruction. Combined RAGE- and ICAM-1-blocking strategies may prove beneficial in neonatal obstructive nephropathy.

RAGE

Knockout mouse

10.1038/ki.2013.171

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Citations (35)

Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.

Journal of the American Society of Nephrology (1998)

Lutz T. Weber Maria Shipkova T. Lamersdorf P. D. Niedmann M. Wiesel

Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.

Mycophenolate

Free fraction

10.1681/asn.v981511

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Citations (216)

Harnwegsinfektionen im Säuglings- und Kindesalter

Elsevier eBooks (2023)

Marcus R. Benz Lutz T. Weber

10.1016/b978-3-437-23817-8.00072-0

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Citations (0)

Can we minimize the long-term side effects of immunosuppressive drugs in pediatric patients?