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Risk factors and clinical characteristics of tacrolimus-induced acute nephrotoxicity in children with nephrotic syndrome: a retrospective case-control study

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Abstract

Purpose

Acute nephrotoxicity is a common adverse reaction of tacrolimus therapy; however, its risk factors in pediatric nephrotic syndrome (NS) remain to be evaluated. The objective of this study was to investigate the risk factors and characteristics of tacrolimus-induced acute nephrotoxicity in children with NS.

Methods

Past records of children with NS admitted to our hospital from 2014 to 2018 were reviewed. The incidence and characteristics of nephrotoxicity were analyzed. Multivariate logistic regression analysis was used to identify the risk factors of nephrotoxicity. A clinically applicable risk score was developed and validated.

Results

Tacrolimus-induced nephrotoxicity occurred in 25 of 129 patients, 13 patients were grade 1, and the renal function was recovered in 22 patients. Multivariate regression analysis showed that the maximum trough concentrations (C12h) of tacrolimus (OR, 1.48; 95% CI, 1.16 to 1.88; P < 0.001), huaiqihuang granules (OR, 0.095; 95% CI, 0.014 to 0.66; P = 0.017), and diarrhea (OR, 22.00; 95% CI, 1.58 to 306.92; P = 0.022) were independently associated with tacrolimus-induced nephrotoxicity. The maximum C12h were significantly higher in patients with nephrotoxicity (median 9.0 ng/ml) and the cut-off value for acute nephrotoxicity was 6.5 ng/ml. The area under the receiver operating characteristic curve was 0.821 for the proposed model based on the observations used to create the model and 0.817 obtained from k-fold cross-validation.

Conclusions

High trough concentration of tacrolimus and diarrhea can potentiate the risk of tacrolimus-induced acute nephrotoxicity in children with NS, while huaiqihuang granules can protect this condition.

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Funding

This work was supported by grants from the Wuhan Health and Family Planning Commission (No. WZ18Q03 to P.G.) and National Natural Scientific Foundation of China (NSFC, No.81803503 to X.L.G.; No. 71874062 to R.H.).

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Ping Gao, Mao-Chang Liu & Hua Xu

  2. Department of Pharmacy, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xin-Lei Guan

  3. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Rui Huang & Xiao-Fang Shang-guan

  4. Department of Nephrology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Jiang-Wei Luan & Xiao-Wen Wang

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  1. Ping Gao
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  2. Xin-Lei Guan
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Contributions

PG, HX, and XW planned the study; PG and XG collected the data and wrote the manuscript; RH and XS carried out the statistical analyses; JL and ML contributed to the interpretation of the data. All authors contributed to, and have approved, the final manuscript.

Corresponding authors

Correspondence to Hua Xu or Xiao-Wen Wang.

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The study was approved by the local ethical committees of Wuhan Children’s Hospital.

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Gao, P., Guan, XL., Huang, R. et al. Risk factors and clinical characteristics of tacrolimus-induced acute nephrotoxicity in children with nephrotic syndrome: a retrospective case-control study. Eur J Clin Pharmacol 76, 277–284 (2020). https://doi.org/10.1007/s00228-019-02781-3

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