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Remote ischemic preconditioning upregulates microRNA-21 to protect the kidney in children with congenital heart disease undergoing cardiopulmonary bypass

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Abstract

Background

Acute kidney injury (AKI) is one of the most common emergencies and severe diseases in the clinic. We sought to verify whether remote ischemic preconditioning (RIPC) has a protective effect on the kidney of child with congenital heart disease undergoing cardiopulmonary bypass (CPB) surgery. We hypothesized it may be related to the up-regulation of microRNA-21 (miR-21).

Methods

We performed a prospective randomized clinical study among children with congenital heart disease undergoing CPB surgery between January and December 2016. Children were randomized to an RIPC or control group. Patients in each group were divided into an AKI and a non-AKI group according to the occurrence of AKI at 48 h after surgery. Remote ischemic preconditioning (RIPC) conducted by blood-pressure cuff was performed 12 h before surgery. Serum creatinine (SCr), tumor necrosis factor-α (TNF-α), and miR-21 expression in blood and urine were measured at different time points.

Results

A total of 449 cases (200 RIPC; 249 controls) were enrolled. The male/female ratio was 1.18, with a mean age of 37.50 ± 25.31 months. The incidence of AKI in the RIPC group was significantly lower than that in the control group (19.0% vs. 46.2%, P<0.01). In further analysis, at 6 h, 24 h, and 48 h after CPB operation, blood TNF-α levels were significantly lower in the RIPC group than in the control group (P<0.01); at 24 h, 48 h, and 72 h, urine TNF-α levels were significantly lower in the RIPC group than in the control group (P<0.05). Urine and blood miR-21 expression in the RIPC group increased significantly, while there was no obvious change in the control group.

Conclusions

Remote ischemic preconditioning has a protective effect on the kidney in children with congenital heart disease, which may be related with the up-regulation of miR-21 and down-regulating the inflammatory mediator, such as TNF-α.

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Acknowledgements

The study was supported by grants from the Natural Science Fund of Hunan Province (2015JJ4029) and Clinical Center for Acute Renal Injury in Children of Hunan Province.

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Authors and Affiliations

  1. Department of Nephrology and Rheumatology of Hunan Children’s Hospital, 86 Ziyuan Road, Changsha, Hunan, 410007, People’s Republic of China

    Zhijuan Kang, Zhihui Li, Ying Wang, Tuanhong Xia & Yuhang Zhou

  2. Academy of Pediatrics of University of South China, 86 Ziyuan Road, Changsha, Hunan, 410007, People’s Republic of China

    Zhijuan Kang, Zhihui Li, Ying Wang, Tuanhong Xia & Yuhang Zhou

  3. Department of Cardiothoracic Surgery of Hunan Children’s Hospital, 86 Ziyuan Road, Changsha, Hunan, 410007, People’s Republic of China

    Peng Huang, Jinwen Luo & Pingbo Liu

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  1. Zhijuan Kang
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Correspondence to Zhihui Li.

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Ethical considerations

The study complies with the Helsinki declaration and was approved by the local institutional ethics committee of the Hunan Children’s Hospital (ICF2015004), dated 25 November 2015. Informed consent from potential trial participants was obtained from a parent or guardian before enrollment. The model consent form Version 01 dated 5 September 2015 is available under Additional file. Patients could discontinue participation at any time upon request. The study is registered with the Chinese Clinical Trial Registry (registration ID: ChiCTR-IOC-15007513).

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The authors declare no conflict of interest.

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Kang, Z., Li, Z., Huang, P. et al. Remote ischemic preconditioning upregulates microRNA-21 to protect the kidney in children with congenital heart disease undergoing cardiopulmonary bypass. Pediatr Nephrol 33, 911–919 (2018). https://doi.org/10.1007/s00467-017-3851-9

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  • DOI: https://doi.org/10.1007/s00467-017-3851-9

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