Background: Abnormalities in mineral metabolism are common complications of organ transplantation. The role of immunosuppressive agents in alteration of mineral metabolism is not clear.
Methods: We conducted an animal study to investigate the effects of cyclosporine A (CsA), tacrolimus, and sirolimus on renal calcium, magnesium and vitamin D metabolism.
Results: CsA and tacrolimus induced a 2- to 3-fold and 1.6- to 1.8-fold increase in urinary calcium and magnesium excretion, respectively, while rapamycin had no effects on calcium, but doubled the urinary magnesium excretion. CsA and tacrolimus, but not rapamycin, elevated serum 1,25(OH)(2) vitamin D without affecting the parathyroid hormone level. CsA and tacrolimus reduced mRNA abundance in TRPV5 (CsA: 64 ± 3% of control; tacrolimus: 50 ± 3%) calbindin-D28k (CsA: 62 ± 4%; tacrolimus: 43 ± 3%), and vitamin D receptor (CsA: 52 ± 3%; tacrolimus: 58 ± 2%, all p < 0.05). Rapamycin did not affect gene expression in any of studied proteins. The immunofluorescence staining study demonstrated a 50% reduction of TRPV5 and calbindin-D28k by CsA and tacrolimus.
Conclusion: The suppression of VDR by calcineurin inhibitors is probably the underlying mechanism of renal calcium wasting. In spite of an increased 1,25(OH)(2) vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265419 | PMC |
| http://dx.doi.org/10.1159/000328874 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The safety of cyclosporine and tacrolimus in pediatric nephrotic syndrome patients: a disproportionate analysis based on the FAERS database.
Front Pediatr
January 2025
Department of Urology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, China.
Objective: This study aimed to systematically evaluate the safety of cyclosporine (CsA) and tacrolimus (TAC) in pediatric nephrotic syndrome (NS) patients using real-world data from the FDA Adverse Event Reporting System (FAERS).
Methods: We analyzed adverse event (AE) reports from the FAERS database between Q4 2003 and Q2 2024, focusing on AEs associated with CsA and TAC in NS patients aged 18 years and younger. We employed three signal detection methods-Proportional Reporting Ratio (PRR), Relative Reporting Ratio (RRR), and Reporting Odds Ratio (ROR)-to assess the risk of drug-related AEs.
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 PDFStructure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry, Duke University, Durham, NC 27708.
Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.
View Article and Find Full Text PDFEfficacy and safety of nine immunosuppressive agents for primary focal segmental glomerulosclerosis in adults: a pairwise and network meta-analysis.
Ren Fail
December 2024
Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.
Background: Immunosuppressants are widely used as the preferred treatment for primary focal segmental glomerulosclerosis (pFSGS). Nevertheless, controversies persist regarding the effectiveness and side effects of different immunosuppressive medications.
Methods: From July 2023 until June 2024, we systematically searched PubMed, Cochrane Library, Web of Science, clinicalrials.
Dried Blood Spot Sampling for Monitoring Children With Immune-Mediated Glomerulopathies and After Kidney Transplantation.
Kidney Int Rep
November 2024
Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Introduction: Monitoring kidney function and immunosuppressant levels in children post-kidney transplantation or those with glomerulopathies is challenging due to frequent venipunctures and clinic visits. Capillary dried blood spot sampling (DBS) offers a potential alternative.
Methods: In this prospective single-center study, 89 children (38% female and 62% male) requiring therapeutic drug monitoring (TDM) and kidney function assessment were enrolled.
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!