Abu Bakar, Karmila and Mohamad, Nor Asiah and Hodi, Zsolt and McCulloch, Tom and Williams, Alun and Christian, Martin and Key, Tim and Kim, Jon Jin (2019) Defining a threshold for tacrolimus intra-patient variability associated with late acute cellular rejection in paediatric kidney transplant recipients. Pediatric Nephrology, 34 (12). pp. 2557-2562. ISSN 0931-041X, DOI https://doi.org/10.1007/s00467-019-04346-z.
Full text not available from this repository.Abstract
Background: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known. Methods: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels < 4 μg/L (Tac < 4) and the concentration/weight-adjusted dose (C/D) ratio as a proxy marker of tacrolimus metaboliser status. Results: LACR patients had higher CV (median, IQR 44%, 36–61% v. 24%, 19–35%, p < 0.0001) and higher MAD (33%, 25–48% v. 19%, 15–26%, p < 0.0001). The MAD was less affected by outlying tacrolimus results. Receiver operating curve analysis of the MAD resulted in a sensitivity of 76% and specificity of 76% at a threshold of 26% (AUC 0.85, p < 0.05). LACR patients had more Tac < 4 (50% v. 26%, p < 0.05). There was no difference in C/D suggesting that good IPV can be maintained in fast metabolisers. Patients with LACR had significantly increased creatinine at 12-month follow-up despite treatment (108 v. 5 umol/L increase from baseline) and four patients lost their allograft. Conclusions: Monitoring of tacrolimus IPV using the MAD may be a clinical marker for LACR. A threshold IPV of 26% can potentially be used as a therapeutic target pending further validation studies. © 2019, IPNA.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Graft survival; Intra-patient variability; Non-adherence; Rejection; Tacrolimus |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 18 May 2020 02:18 |
| Last Modified: | 18 May 2020 02:18 |
| URI: | http://eprints.um.edu.my/id/eprint/24292 |
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