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Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy

BACKGROUND: Accelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN. METHODS: We included a retrosp...

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Autores principales: Dai, Huanzi, Hu, Wei, Lin, Lirong, Wang, Liming, Chen, Jia, He, Yani
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087134/
https://www.ncbi.nlm.nih.gov/pubmed/33959273
http://dx.doi.org/10.1093/ckj/sfaa257
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author Dai, Huanzi
Hu, Wei
Lin, Lirong
Wang, Liming
Chen, Jia
He, Yani
author_facet Dai, Huanzi
Hu, Wei
Lin, Lirong
Wang, Liming
Chen, Jia
He, Yani
author_sort Dai, Huanzi
collection PubMed
description BACKGROUND: Accelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN. METHODS: We included a retrospective cohort of 105 patients with biopsy-proven IgAN. Tubular DcR2 expression was assessed at renal biopsy and the Oxford histological MEST-C score [mesangial hypercellularity (M), endocapillary proliferation (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C)] defined disease severity. IgAN progression was defined as a composite of end-stage renal disease or a 30% decline in the estimated glomerular filtration rate (eGFR), analyzed using Kaplan–Meier and Cox regression analyses. RESULTS: Tubular DcR2 was overexpressed in IgAN. Numbers of DcR2 and p16 double-positive RTECs increased with increasing severity of tubular atrophy/interstitial fibrosis (T lesion). Patients with ≥25% tubular DcR2 expression experienced worse proteinuria, T lesions and a lower eGFR. Cumulative renal survival was significantly lower in patients with ≥25% DcR2 positivity. Multivariate regression analyses showed that ≥25% tubular DcR2 expression was significantly associated with worse eGFR slopes (the rate of renal function decline; P = 0.003) and the incidence of the composite outcome (P = 0.001) in IgAN. The addition of tubular DcR2 to a model with clinical data at biopsy (mean arterial pressure, proteinuria and eGFR) or MEST-C score significantly improved the 5-year risk prediction of IgAN progression, as confirmed by receiver operating characteristic curve analyses. CONCLUSIONS: Tubular DcR2 expression detected at biopsy was a strong independent predictor for IgAN progression and might have prognostic value in addition to established risk markers.
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spelling pubmed-80871342021-05-05 Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy Dai, Huanzi Hu, Wei Lin, Lirong Wang, Liming Chen, Jia He, Yani Clin Kidney J Original Articles BACKGROUND: Accelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN. METHODS: We included a retrospective cohort of 105 patients with biopsy-proven IgAN. Tubular DcR2 expression was assessed at renal biopsy and the Oxford histological MEST-C score [mesangial hypercellularity (M), endocapillary proliferation (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C)] defined disease severity. IgAN progression was defined as a composite of end-stage renal disease or a 30% decline in the estimated glomerular filtration rate (eGFR), analyzed using Kaplan–Meier and Cox regression analyses. RESULTS: Tubular DcR2 was overexpressed in IgAN. Numbers of DcR2 and p16 double-positive RTECs increased with increasing severity of tubular atrophy/interstitial fibrosis (T lesion). Patients with ≥25% tubular DcR2 expression experienced worse proteinuria, T lesions and a lower eGFR. Cumulative renal survival was significantly lower in patients with ≥25% DcR2 positivity. Multivariate regression analyses showed that ≥25% tubular DcR2 expression was significantly associated with worse eGFR slopes (the rate of renal function decline; P = 0.003) and the incidence of the composite outcome (P = 0.001) in IgAN. The addition of tubular DcR2 to a model with clinical data at biopsy (mean arterial pressure, proteinuria and eGFR) or MEST-C score significantly improved the 5-year risk prediction of IgAN progression, as confirmed by receiver operating characteristic curve analyses. CONCLUSIONS: Tubular DcR2 expression detected at biopsy was a strong independent predictor for IgAN progression and might have prognostic value in addition to established risk markers. Oxford University Press 2021-01-27 /pmc/articles/PMC8087134/ /pubmed/33959273 http://dx.doi.org/10.1093/ckj/sfaa257 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Dai, Huanzi
Hu, Wei
Lin, Lirong
Wang, Liming
Chen, Jia
He, Yani
Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy
title Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy
title_full Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy
title_fullStr Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy
title_full_unstemmed Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy
title_short Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy
title_sort tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin a nephropathy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087134/
https://www.ncbi.nlm.nih.gov/pubmed/33959273
http://dx.doi.org/10.1093/ckj/sfaa257
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