Ping Gao1, Xin-Lei Guan2, Rui Huang3, Xiao-Fang Shang-Guan3, Jiang-Wei Luan4, Mao-Chang Liu1, Hua Xu5, Xiao-Wen Wang6. 1. Department of Clinical Pharmacy, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Pharmacy, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 3. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Department of Nephrology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 5. Department of Clinical Pharmacy, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 690680952@qq.com. 6. Department of Nephrology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. wangxiaowen_hust@163.com.
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.
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.
Authors: C A Naranjo; U Busto; E M Sellers; P Sandor; I Ruiz; E A Roberts; E Janecek; C Domecq; D J Greenblatt Journal: Clin Pharmacol Ther Date: 1981-08 Impact factor: 6.875
Authors: Lakhmir S Chawla; Rinaldo Bellomo; Azra Bihorac; Stuart L Goldstein; Edward D Siew; Sean M Bagshaw; David Bittleman; Dinna Cruz; Zoltan Endre; Robert L Fitzgerald; Lui Forni; Sandra L Kane-Gill; Eric Hoste; Jay Koyner; Kathleen D Liu; Etienne Macedo; Ravindra Mehta; Patrick Murray; Mitra Nadim; Marlies Ostermann; Paul M Palevsky; Neesh Pannu; Mitchell Rosner; Ron Wald; Alexander Zarbock; Claudio Ronco; John A Kellum Journal: Nat Rev Nephrol Date: 2017-02-27 Impact factor: 28.314
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