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Inflammatory biomarkers in staging of chronic kidney disease: elevated TNFR2 levels accompanies renal function decline

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Abstract

Background

Inflammation is a common feature in the pathogenesis of chronic kidney disease (CKD), regardless of the disease cause. Our aim was to evaluate the potential of several inflammatory biomarkers in CKD diagnosis and staging.

Methods

A total of 24 healthy controls and 92 pre-dialysis CKD patients with diverse etiologies, were enrolled in this study and grouped according to their CKD stage. We analysed the circulating levels of inflammatory molecules, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 2 (TNFR2), pentraxin 3 (PTX3) and leptin, as well as the hemogram. We studied their association with parameters of kidney function and kidney injury, to evaluate their potential as early markers of the disease and/or of its worsening, as well as their interplay.

Results

Compared to controls, patients in CKD stages 1–2 presented significantly higher IL-6 and TNFR2 levels, and higher neutrophil-to-lymphocyte ratio. All inflammatory cytokines and acute-phase proteins showed a trend to increase up to stage 3, stabilizing or declining thereafter, save for TNFR2, which steadily increased from stage to stage. All inflammatory molecules, apart from PTX3, were negatively and significantly correlated with eGFR, with a remarkable value for TNFR2 (r = − 0.732, p < 0.001).

Conclusion

TNFR2 might be useful for an early detection of CKD, as well as for disease staging/worsening. Still, the potential value of this biomarker in disease progression warrants further investigation.

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Acknowledgements

This work was supported by Applied Molecular Biosciences Unit (UCIBIO), which is financed by national funds from FCT & MCTES; by FEDER COMPETE2020 funds UIDP/04539/2020 (CIBB); by PTDC/SAU-NUT/31712/2017, POCI-01-0145-FEDER-007440 and POCI-01-0145-FEDER-031712, and by FCT doctoral grant SFRH/BD/145939/2019; by funds from Portugal Regional Coordination and Development Commissions (Norte-01-0145-FEDER-000024; Centro-01-0145-FEDER-000012); by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher [(S. Rocha – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322)].

Funding

This work was financially supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.

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Authors and Affiliations

  1. UCIBIO – Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, E2, P5, 4050-313, Porto, Portugal

    Irina Lousa, Luís Belo, Maria João Valente, Petronila Rocha-Pereira & Alice Santos-Silva

  2. Associate Laboratory i4HB – Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal

    Irina Lousa, Luís Belo, Maria João Valente, Petronila Rocha-Pereira & Alice Santos-Silva

  3. LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050- 313, Porto, Portugal

    Susana Rocha

  4. Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548, Coimbra, Portugal

    Inês Preguiça & Flávio Reis

  5. Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504, Coimbra, Portugal

    Inês Preguiça & Flávio Reis

  6. Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-075, Coimbra, Portugal

    Inês Preguiça & Flávio Reis

  7. Health Sciences Research Center, University of Beira Interior, 6200-506, Covilhã, Portugal

    Petronila Rocha-Pereira

  8. Porto University Hospital Center, 4099-001, Porto, Portugal

    Idalina Beirão

  9. ICBAS, School of Medicine and Biomedical Sciences, University of Porto, 4050-313, Porto, Portugal

    Idalina Beirão

  10. Nephrology Department, Coimbra University Hospital Center, 3004-561, Coimbra, Portugal

    Filipe Mira & Rui Alves

  11. University Clinic of Nephrology, Faculty of Medicine, University of Coimbra, 3000-075, Coimbra, Portugal

    Rui Alves

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  1. Irina Lousa
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  2. Luís Belo
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  3. Maria João Valente
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  4. Susana Rocha
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  5. Inês Preguiça
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  6. Petronila Rocha-Pereira
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  8. Filipe Mira
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  11. Alice Santos-Silva
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Correspondence to Luís Belo.

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Lousa, I., Belo, L., Valente, M.J. et al. Inflammatory biomarkers in staging of chronic kidney disease: elevated TNFR2 levels accompanies renal function decline. Inflamm. Res. 71, 591–602 (2022). https://doi.org/10.1007/s00011-022-01574-2

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  • DOI: https://doi.org/10.1007/s00011-022-01574-2

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