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Published on: April 13, 2021
Kidney adverse events associated with calcineurin inhibitors: a real-world study based on the FAERS database and
YaoYun Liang1, XinYu Tan1, Qian Dai2
1Department of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Objective:
This study utilized FDA Adverse Event Reporting System (FAERS) data and network pharmacology methods to evaluate the risk of renal adverse events (AEs) associated with calcineurin inhibitors (CNIs), providing guidance for safe drug use.
Method:
By analyzing FAERS data from 2004 to 2024, we identified renal AEs associated with CNI therapy. We employed imbalance analysis (report odds ratio [ROR], proportion of reports ratio [PRR], MGPS, and Bayesian confidence propagation neural network [BCPNN]) to detect signals and explored drug-gene interaction networks to investigate potential mechanisms.
Results:
Revealed significant associations between cyclosporine, tacrolimus, and voclosporin with renal injury, with voclosporin showing stronger correlations (ROR = 5.24, PRR = 4.85, EBGM05 = 4.85, IC025 = 2.28) but lower mortality rates. Network pharmacology analysis suggested that cyclosporine, tacrolimus, and everolimus may exert their toxic effects by acting on core genes.
Conclusion:
The widespread use of CNIs raises concerns about their renal safety. This study provides new evidence from real-world data indicating differences in renal toxicity risk and mechanisms among calcineurin inhibitors (CNIs), underscoring the importance of pharmacovigilance strategies for patients with autoimmune diseases.
Insights
Calcineurin inhibitors (CNIs) like cyclosporine and tacrolimus are linked to kidney damage. Voclosporin also shows renal risk but with lower mortality, highlighting the need for careful CNI monitoring.
Area of Science:
- Pharmacology
- Nephrology
- Drug Safety
Background:
- Calcineurin inhibitors (CNIs) are crucial immunosuppressants.
- Concerns exist regarding their renal safety, particularly in autoimmune disease patients.
- Understanding differential renal risks is vital for patient management.
Purpose of the Study:
- To evaluate renal adverse events (AEs) associated with calcineurin inhibitors (CNIs) using real-world data.
- To compare the renal toxicity profiles of different CNIs.
- To explore potential mechanisms underlying CNI-induced nephrotoxicity.
Main Methods:
- Analysis of FDA Adverse Event Reporting System (FAERS) data (2004-2024).
- Application of pharmacovigilance signal detection methods (ROR, PRR, MGPS, BCPNN).
- Network pharmacology to investigate drug-gene interactions and toxicological pathways.
Main Results:
- Significant associations found between cyclosporine, tacrolimus, and voclosporin with renal injury.
- Voclosporin demonstrated stronger renal risk signals but lower mortality rates compared to others.
- Network analysis implicated core genes in the nephrotoxic mechanisms of CNIs.
Conclusions:
- Real-world data reveal varying renal toxicity risks among CNIs.
- Differences in toxicity mechanisms exist, necessitating tailored pharmacovigilance.
- This study informs safer CNI use in clinical practice, especially for autoimmune conditions.
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