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. 2025 Feb 26;23(1):123.
doi: 10.1186/s12916-025-03936-z.

Sensitivity to thyroid hormones in children developing acute kidney injury at the onset of type 1 diabetes mellitus

Stefano Guarino  1 , Valeria Calcaterra  2   3 , Anna Di Sessa  1 , Lucia Labati  3   4 , Maria Maddalena Marrapodi  1 , Anna Grandone  1 , Angela Zanfardino  1 , Gianvincenzo Zuccotti  3   4 , Dario Iafusco  1 , Emanuele Miraglia Del Giudice  1 , Pierluigi Marzuillo  5
Affiliations

Sensitivity to thyroid hormones in children developing acute kidney injury at the onset of type 1 diabetes mellitus

Stefano Guarino et al. BMC Med. .

Abstract

Background: Thyroid hormone (TH) sensitivity at type 1 diabetes mellitus (T1DM) onset and its connection with acute kidney injury (AKI) has not been investigated. We aimed to evaluate changes in TH sensitivity in children with and without AKI at T1DM onset and to assess the role of euthyroid sick syndrome (ESS) in this relationship.

Methods: We included 161 children with new-onset T1DM and followed them until renal function normalized. The free triiodothyronine (FT3)/free thyroxine (FT4) ratio was used to assess peripheral TH sensitivity, while the TSH index (TSHI), thyrotroph T4 resistance index (TT4RI), thyrotroph T3 resistance index (TT3RI), Thyroid Feedback Quantile-based Index (TFQI), and parametric TFQI (PTFQI) were used for central sensitivity.

Results: Patients with AKI exhibited greater weight loss, higher serum ketones, creatinine, corrected sodium, and glycated hemoglobin, but lower bicarbonate and estimated glomerular filtration rate compared to those without AKI. Logistic regression showed that the odds of AKI increased by 11.5-fold for each unit decrease in TFQI, 4.0-fold per unit decrease in PTFQI, and 1.7-fold per unit decrease in TSHI, adjusting for age and gender. After adjusting for age, gender, and ESS, the odds for AKI significantly increased (4.8-fold for each 1-unit decrease) only for TFQI.

Conclusions: AKI at the onset of T1DM has a dual effect on TH. It reduces peripheral sensitivity while increasing central sensitivity. This effect appears to be largely driven by ESS, with the exception of the association between AKI and TFQI, which remains independent of ESS.

Keywords: Acute kidney injury; Euthyroid sick syndrome; Sensitivity; Thyroid hormones; Type 1 diabetes mellitus.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Research Ethics Committee of Università degli Studi della Campania “Luigi Vanvitelli” (approval number 368). The investigation conforms to the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from the parents of the patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Odds ratio of AKI at T1DM onset based on thyroid sensitivity indices, adjusted for age and gender (A) and adjusted for age, gender, and ESS (B). The displayed OR represents a reduction of 1 unit for each parameter, except for the FT3/FT4 ratio, where it reflects a reduction of 0.1 unit. Abbreviations: AKI, acute kidney injury; ESS, euthyroid sick syndrome; FT3, free triiodothyronine; FT4, free thyroxine; TFQI, parametric TFQI; T1DM, type 1 diabetes mellitus; TFQI, Thyroid Feedback Quantile-based Index; TSH, thyroid-stimulating hormone; TSHI, TSH index; TT3RI, thyrotroph T3 resistance index; TT4RI, thyrotroph T4 resistance index
See this image and copyright information in PMC

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