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HMGB-1 and TGFβ-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome

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Abstract

Introduction

Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the basal membranes and renal dysfunction. The purpose of the study was to evaluate urinary (u) and serum (s) levels of tumor growth factor (TGF)-beta(β) and high mobility group box (HMGB)-1 in ALP patients with normal renal function, albuminuria and proteinuria.

Methods

A prospective, single-center study was performed with a follow-up period of 12 months, enrolling 11 pediatric ALP patients and 10 healthy subjects (HS). Normal values of serum creatinine, albuminuria and proteinuria, as well as unaltered estimated glomerular filtration rate (eGFR) were required at enrollment.

Results

ALP patients had significantly higher levels of serum and urinary HMGB1 compared to HS. The same trend was observed for TGF-β1, with higher values in ALP patients than in HS. HMGB1 and TGF-β1 correlated with each other and with markers of renal function and damage. Urinary biomarkers did not correlate with eGFR, whereas sHMGB1 and sTGF-β1 were negatively related to filtration rate (r: − 0.66; p = 0.02, r: − 0.96; p < 0.0001, respectively). Using proteinuria as a dependent variable in a multiple regression model, only the association with sTGF-β1 (β = 0.91, p < 0.0001) remained significant.

Conclusions

High levels of HMGB1 and TGF-β1 characterized ALP patients with normal renal function, highlighting the subclinical pro-fibrotic and inflammatory mechanisms triggered before the onset of proteinuria. Further studies are needed to evaluate the role of HMGB1 and TGFβ-1 in ALP patients.

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Availability of data and material

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

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Pediatric Nephrology and Dialysis Unit, University Hospital “G. Martino”, Messina, Italy

    R. Chimenz, V. Chirico, P. Basile, A. Carcione & G. Conti

  2. Nephrology and Dialysis Unit, Papardo Hospital, Messina, Italy

    P. Monardo & A. Lacquaniti

Authors
  1. R. Chimenz
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  2. V. Chirico
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  3. P. Basile
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  4. A. Carcione
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  5. G. Conti
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  6. P. Monardo
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  7. A. Lacquaniti
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Correspondence to R. Chimenz.

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The study was approved by the Local Ethics Committee for Medical Research and carried out in accordance with the Helsinki Declaration.

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Both parents of each patient provided informed consent permitting data sampling and analysis at the time of initiation of the study.

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Both parents of each patient provided consent fort the publication of data at the time of initiation of the study.

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Chimenz, R., Chirico, V., Basile, P. et al. HMGB-1 and TGFβ-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome. J Nephrol 34, 1915–1924 (2021). https://doi.org/10.1007/s40620-021-01015-z

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  • DOI: https://doi.org/10.1007/s40620-021-01015-z

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