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Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex and involves both glomerular and tubular dysfunction. A global assessment of kidney function is necessary to stage DKD, a progressive kidney disease that is likely to begin in childhood. The present study evaluated whether kidn...

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Autores principales: Zeni, Letizia, Norden, Anthony G. W., Prandi, Elena, Canepa, Carolina, Burling, Keith, Simpson, Katherine, Felappi, Barbara, Plebani, Alessandro, Cancarini, Giovanni, Ferraro, Pietro Manuel, Fraser, Donald, Unwin, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097324/
https://www.ncbi.nlm.nih.gov/pubmed/35550634
http://dx.doi.org/10.1186/s13098-022-00839-4
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author Zeni, Letizia
Norden, Anthony G. W.
Prandi, Elena
Canepa, Carolina
Burling, Keith
Simpson, Katherine
Felappi, Barbara
Plebani, Alessandro
Cancarini, Giovanni
Ferraro, Pietro Manuel
Fraser, Donald
Unwin, Robert J.
author_facet Zeni, Letizia
Norden, Anthony G. W.
Prandi, Elena
Canepa, Carolina
Burling, Keith
Simpson, Katherine
Felappi, Barbara
Plebani, Alessandro
Cancarini, Giovanni
Ferraro, Pietro Manuel
Fraser, Donald
Unwin, Robert J.
author_sort Zeni, Letizia
collection PubMed
description BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex and involves both glomerular and tubular dysfunction. A global assessment of kidney function is necessary to stage DKD, a progressive kidney disease that is likely to begin in childhood. The present study evaluated whether kidney injury biomarkers identified as early DKD biomarkers in adults have any prognostic value in the very early stages of childhood diabetes. METHODS: We measured urine free Retinol-binding protein 4 (UfRBP4), albumin (UAlb), Kidney injury molecule-1 (KIM-1) and the microRNAs miR-155, miR-126 and miR-29b in two cohorts of paediatric T1DM patients without evidence of DKD, but with diabetes of short-duration, ≤ 2.5 years (SD, n = 25) or of long-duration, ≥ 10 years (LD, n = 29); non-diabetic siblings (H, n = 26) were recruited as controls. A p value < 0.05 was considered significant for all results. RESULTS: UfRBP4 and UAlb were not significantly different across the three groups. No differences were found in KIM-1 excretion between any of the three groups. UfRBP4 was correlated with UAlb in all three groups (r 0.49; p < 0.001), whereas KIM-1 showed no correlation with albumin excretion. Among microRNAs, miR-29b was higher in all diabetic children compared with the H control group (p = 0.03), whereas miR-155 and miR-126 were not significantly different. No differences were found between the SD and LD groups for all three microRNAs. No associations were identified between these biomarkers with sex, age, BMI, eGFR, T1DM duration or glycaemic control. CONCLUSIONS: UfRBP4, KIM-1, miR-155, and miR-126 were unaffected by the presence and duration of diabetes, whereas miR-29b showed a modest elevation in diabetics, regardless of duration. These data support the specificity of a panel of urine biomarkers as DKD biomarkers, rather than any relationship to diabetes per se or its duration, and not as early DKD biomarkers in a paediatric setting. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-022-00839-4.
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spelling pubmed-90973242022-05-13 Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration Zeni, Letizia Norden, Anthony G. W. Prandi, Elena Canepa, Carolina Burling, Keith Simpson, Katherine Felappi, Barbara Plebani, Alessandro Cancarini, Giovanni Ferraro, Pietro Manuel Fraser, Donald Unwin, Robert J. Diabetol Metab Syndr Research BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex and involves both glomerular and tubular dysfunction. A global assessment of kidney function is necessary to stage DKD, a progressive kidney disease that is likely to begin in childhood. The present study evaluated whether kidney injury biomarkers identified as early DKD biomarkers in adults have any prognostic value in the very early stages of childhood diabetes. METHODS: We measured urine free Retinol-binding protein 4 (UfRBP4), albumin (UAlb), Kidney injury molecule-1 (KIM-1) and the microRNAs miR-155, miR-126 and miR-29b in two cohorts of paediatric T1DM patients without evidence of DKD, but with diabetes of short-duration, ≤ 2.5 years (SD, n = 25) or of long-duration, ≥ 10 years (LD, n = 29); non-diabetic siblings (H, n = 26) were recruited as controls. A p value < 0.05 was considered significant for all results. RESULTS: UfRBP4 and UAlb were not significantly different across the three groups. No differences were found in KIM-1 excretion between any of the three groups. UfRBP4 was correlated with UAlb in all three groups (r 0.49; p < 0.001), whereas KIM-1 showed no correlation with albumin excretion. Among microRNAs, miR-29b was higher in all diabetic children compared with the H control group (p = 0.03), whereas miR-155 and miR-126 were not significantly different. No differences were found between the SD and LD groups for all three microRNAs. No associations were identified between these biomarkers with sex, age, BMI, eGFR, T1DM duration or glycaemic control. CONCLUSIONS: UfRBP4, KIM-1, miR-155, and miR-126 were unaffected by the presence and duration of diabetes, whereas miR-29b showed a modest elevation in diabetics, regardless of duration. These data support the specificity of a panel of urine biomarkers as DKD biomarkers, rather than any relationship to diabetes per se or its duration, and not as early DKD biomarkers in a paediatric setting. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-022-00839-4. BioMed Central 2022-05-12 /pmc/articles/PMC9097324/ /pubmed/35550634 http://dx.doi.org/10.1186/s13098-022-00839-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zeni, Letizia
Norden, Anthony G. W.
Prandi, Elena
Canepa, Carolina
Burling, Keith
Simpson, Katherine
Felappi, Barbara
Plebani, Alessandro
Cancarini, Giovanni
Ferraro, Pietro Manuel
Fraser, Donald
Unwin, Robert J.
Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
title Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
title_full Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
title_fullStr Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
title_full_unstemmed Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
title_short Exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with Type 1 diabetes mellitus of differing duration
title_sort exploration of a panel of urine biomarkers of kidney disease in two paediatric cohorts with type 1 diabetes mellitus of differing duration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097324/
https://www.ncbi.nlm.nih.gov/pubmed/35550634
http://dx.doi.org/10.1186/s13098-022-00839-4
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