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Kidney Week

Abstract: FR-PO1030

Evaluation of Everolimus Pharmacokinetic Monitoring Based on Trough Concentration and Area Under the Curve (AUC) in Kidney Transplantation

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Fukae, Shota, The University of Osaka Graduate School of Medicine, Suita, Japan
  • Matsumura, Soichi, The University of Osaka Graduate School of Medicine, Suita, Japan
  • Kawamura, Masataka, The University of Osaka Graduate School of Medicine, Suita, Japan
  • Nakazawa, Shigeaki, The University of Osaka Graduate School of Medicine, Suita, Japan
  • Kakuta, Yoichi, The University of Osaka Graduate School of Medicine, Suita, Japan
  • Nonomura, Norio, The University of Osaka Graduate School of Medicine, Suita, Japan
Background

Everolimus (EVR) is an immunosuppressant used in kidney transplantation, offering potential benefits including reduced nephrotoxicity from calcineurin inhibitors (CNIs) and antiviral/antitumor effects. Although therapeutic drug monitoring (TDM) based on trough levels is common, data on EVR pharmacokinetics and adverse events remain limited.

Methods

We analyzed 838 pharmacokinetic data points from 171 kidney transplant recipients managed at the University of Osaka. EVR levels were measured at 0 (C0), 1, 2, 3, and 4 hours post-dose. Area under the concentration-time curve from 0 to 4 hours (AUC0-4) was calculated. We assessed correlations between EVR levels and AUC0-4 and evaluated associations with proteinuria and de novo hyperlipidemia (HL).

Results

C0 moderately correlated with AUC0-4 (r = 0.524, p < 0.001), while C2 showed the strongest correlation (r = 0.944, p < 0.001). The timing of peak concentration varied: C1 was highest after 3 months post-transplant, whereas C3–C4 peaked within the first 3 months. AUC0-4 was not associated with proteinuria. However, patients who developed de novo HL had significantly higher AUC0-4 values compared to those who did not (28.2 vs. 24.5 ng×h/mL, p < 0.01). Receiver operating characteristics (ROC) analysis for HL prediction based on AUC0-4 showed an AUC of 0.603.

Conclusion

While trough EVR levels showed a correlation with AUC0-4, C2 demonstrated a stronger correlation, indicating that it may more accurately reflect systemic exposure. Moreover, higher AUC0-4 was associated with hyperlipidemia, suggesting its potential as a predictive marker for EVR-related adverse effects in kidney transplant recipients.

Digital Object Identifier (DOI)