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Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock

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Abstract

Background

Studies in critically ill adults demonstrate associations between serum renin concentrations (a proposed surrogate for renin–angiotensin–aldosterone system dysregulation) and poor outcomes, but data in critically ill children are lacking. We assessed serum renin + prorenin concentrations in children with septic shock to determine their predictive ability for acute kidney injury (AKI) and mortality.

Methods

We conducted a secondary analysis of a multicenter observational study of children aged 1 week to 18 years admitted to 14 pediatric intensive care units (PICUs) with septic shock and residual serum available for renin + prorenin measurement. Primary outcomes were development of severe persistent AKI (≥ KDIGO stage 2 for ≥ 48 h) in the first week and 28-day mortality.

Results

Among 233 patients, day 1 median renin + prorenin concentration was 3436 pg/ml (IQR 1452–6567). Forty-two (18%) developed severe persistent AKI and 32 (14%) died. Day 1 serum renin + prorenin predicted severe persistent AKI with an AUROC of 0.75 (95% CI 0.66–0.84, p < 0.0001; optimal cutoff 6769 pg/ml) and mortality with an AUROC of 0.79 (95% CI 0.69–0.89, p < 0.0001; optimal cutoff 6521 pg/ml). Day 3/day 1 (D3:D1) renin + prorenin ratio had an AUROC of 0.73 (95% CI 0.63–0.84, p < 0.001) for mortality. On multivariable regression, day 1 renin + prorenin > optimal cutoff retained associations with severe persistent AKI (aOR 6.8, 95% CI 3.0–15.8, p < 0.001) and mortality (aOR 6.9, 95% CI 2.2–20.9, p < 0.001). Similarly, D3:D1 renin + prorenin > optimal cutoff was associated with mortality (aOR 7.6, 95% CI 2.5–23.4, p < 0.001).

Conclusions

Children with septic shock have very elevated serum renin + prorenin concentrations on PICU admission, and these concentrations, as well as their trend over the first 72 h, predict severe persistent AKI and mortality.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Change history

  • 23 April 2023

    The name Naomi Pode Shakked has been tagged correctly.

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Acknowledgements

The authors thank the late Dr. Hector Wong, the leader of this multicenter study of pediatric septic shock for over a decade and a mentor to all of us. He was intimately involved in the conceptualization of this project, although he tragically passed before the data were analyzed and the manuscript was written. The authors also thank Patrick Lahni and Kelli Harmon for technical assistance in the conduct of this study.

Funding

This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (KL2TR001426). The original study was funded by National Institute of General Medical Sciences, R35GM126943 (PI: Hector R. Wong). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Authors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Natalja L. Stanski, Naomi Pode Shakked & Stuart L. Goldstein

  2. Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Ave, Cincinnati, OH, 45267, USA

    Natalja L. Stanski & Stuart L. Goldstein

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Naomi Pode Shakked

  4. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Bin Zhang

  5. UCSF Benioff Children’s Hospital Oakland, 747 52Nd Street, Oakland, CA, 94609, USA

    Natalie Z. Cvijanovich

  6. The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Julie C. Fitzgerald & Scott L. Weiss

  7. Texas Children’s Hospital and Baylor College of Medicine, 6621 Fannin Street, Houston, TX, 77030, USA

    Parag N. Jain

  8. Children’s Hospital of Orange County, 1201 W La Veta Ave, Orange, CA, 92868, USA

    Adam J. Schwarz

  9. Children’s Minnesota, 2525 Chicago Ave, Minneapolis, MN, 55404, USA

    Jeffrey Nowak

  10. Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Geoffrey L. Allen

  11. Penn State Health Children’s Hospital, 600 University Dr, Hershey, PA, 17033, USA

    Neal J. Thomas

  12. Lucile Packard Children’s Hospital Stanford, 725 Welch Rd, Palo Alto, CA, 94304, USA

    Bereketeab Haileselassie

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  1. Natalja L. Stanski
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Contributions

Conceptualization/methodology/formal analysis and investigation/writing, original draft and preparation: NLS, NPS, BZ, SLG. Data acquisition: NLS, NZC, JCF, PNJ, AJS, JN, GLA, NJT, BH. Writing, review and editing: NLS, NPS, BZ, SLG, NZC, JCF, PNJ, AJS, JN, GLA, NJT, BH. Funding acquisition: NLS.

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Correspondence to Natalja L. Stanski.

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NLS is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (KL2TR001426). JCF is supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (K23DK119463). The remainder of the authors report no financial disclosures or conflict of interest relevant to this work.

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Stanski, N.L., Pode Shakked, N., Zhang, B. et al. Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock. Pediatr Nephrol 38, 3099–3108 (2023). https://doi.org/10.1007/s00467-023-05930-0

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