Background: Recent clinical trials of mycophenolate mofetil (MMF) in chronic allograft nephropathy (CAN) demonstrated that the dose of cyclosporine A (CsA) is one of the critical factors in determining graft function in CAN, but the effect of MMF on chronic CsA nephropathy is undetermined. We undertook this study to evaluate the effect of MMF on CsA-induced nephrotoxicity in an animal model of chronic CsA nephropathy.
Methods: In the first experiment, Sprague-Dawley rats on a low-salt diet were treated with CsA (7.5 mg/kg per day) for 10 weeks, or were treated with CsA for five weeks and then MMF (20 mg/kg per day) was administered five weeks later. In the second experiment, rats were treated with CsA for five weeks, and CsA was then withdrawn for five weeks with or without MMF treatment. Renal function, histologic parameters (tubulointerstitial fibrosis, arteriolopathy, ED-1-positive cells, renin-positive glomeruli, TUNEL-positive cells) and the expression of osteopontin and transforming growth factor (TGF)-beta1 mRNA expressions were compared for different treatment groups.
Results: CsA-treated rats showed decreased renal function and increased histologic parameters compared with the vehicle (VH)-treated rats. The addition of MMF did not improve these parameters compared with the CsA-treated rats. With CsA withdrawal, renal function and histologic parameters were significantly improved compared with the CsA-treated rats, and MMF treatment after CsA withdrawal further improved the histologic parameters. At the molecular level, the addition of MMF did not decrease the expression of osteopontin and transforming growth factor-beta1 (TGF-beta1) mRNAs, which were increased in the CsA-treated rat kidney. With CsA withdrawal, the expression of both mRNAs was significantly decreased compared with the CsA group, and a further decrease was observed with MMF treatment after CsA was withdrawn.
Conclusion: The combined treatment of CsA and MMF does not prevent the development of chronic CsA nephrotoxicity, but MMF treatment after CsA withdrawal does improve chronic CsA nephrotoxicity. This finding provides a rationale for MMF treatment in chronic CsA nephrotoxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1046/j.1523-1755.2002.00400.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies.
Chron Respir Dis
January 2025
South Texas Veterans Health Care System, University of Texas Health, San Antonio, TX, USA.
Background: The efficacy and safety of ensifentrine, a novel PDE3/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens.
Objective: This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS).
Immunosuppressive therapy and nutritional diseases of patients after kidney transplantation: a systematic review.
BMC Nephrol
January 2025
Department of Clinical Dietetics, Medical University of Warsaw, Erazma Ciolka 27 Street, Warsaw, 01-445, Poland.
Background: Kidney transplantation (kTx) is by far the most effective method of treating end-stage renal disease, with immunosuppressive therapy being obligatory for all, except identical twins. Despite kTx being the most effective treatment for end-stage renal disease, the patients face significant morbidity. They are often burdened with diabetes, anaemia, lipid disorders, all of which pose heightened risks for cardiovascular disease.
View Article and Find Full Text PDFMagnetic resonance imaging evaluation of cervical paraspinal muscles in dropped head syndrome.
Eur Spine J
January 2025
Department of Orthopaedic Surgery, Kindai University Hospital, Osaka-Sayama, Japan.
Purpose: The pathomechanism of dropped head syndrome (DHS) is unclear. In this study, we aimed to examine the features of the paraspinal cervical muscles in patients with DHS by analyzing the volume of these muscles using magnetic resonance imaging (MRI).
Methods: Thirty-six patients with DHS and 25 patients with cervical spondylotic myelopathy (controls) were enrolled.
A Computational Fluid Dynamics Analysis of BiPAP Pressure Settings on Airway Biomechanics Using a CT-Based Respiratory Tract Model.
Respir Physiol Neurobiol
January 2025
School of Mechanical and Mechatronic Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW 2007, Australia. Electronic address:
Central and Obstructive Sleep Apnea (CSA and OSA), Chronic Obstructive Pulmonary Disease (COPD), and Obesity Hypoventilation Syndrome (OHS) disrupt breathing patterns, posing significant health risks and reducing the quality of life. Bilevel Positive Airway Pressure (BiPAP) therapy offers adjustable inhalation and exhalation pressures, potentially enhancing treatment adaptability for the above diseases. This is the first-ever study that employs Computational Fluid Dynamics (CFD) to examine the biomechanical impacts of BiPAP under four settings: Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 12/8, 16/6, and 18/8 cmHO, compared to a without-BiPAP scenario of zero-gauge pressure.
View Article and Find Full Text PDFOpioid Prescriptions for Low Back Pain among Military-Connected Older Adults Across Multiple Care Systems.
Drugs Aging
January 2025
Department of Military and Emergency Medicine, Uniformed Services University, Bethesda, MD, USA.
Background: Untreated low back pain (LBP) in older adults can lead to disability and development of chronicity. Due to the potential development of medical comorbidities and negative risks associated with pharmacological use, chronic LBP management for older adults requires a responsive approach.
Methods: The objective of this study is to evaluate the probability of (1) opioid prescription receipt and (2) opioid-sedative coprescription, in a sample of military-service-connected patients enrolled in the Veterans Health Administration (VHA) or TRICARE, ages 30-85 years, receiving care in three systems: VHA, Military Health System (MHS), and nonfederal (civilian) healthcare facilities.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!