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Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy

Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing/preventi...

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Autores principales: Zürbig, Petra, Jerums, George, Hovind, Peter, MacIsaac, Richard J., Mischak, Harald, Nielsen, Stine E., Panagiotopoulos, Sianna, Persson, Frederik, Rossing, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501878/
https://www.ncbi.nlm.nih.gov/pubmed/22872235
http://dx.doi.org/10.2337/db12-0348
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author Zürbig, Petra
Jerums, George
Hovind, Peter
MacIsaac, Richard J.
Mischak, Harald
Nielsen, Stine E.
Panagiotopoulos, Sianna
Persson, Frederik
Rossing, Peter
author_facet Zürbig, Petra
Jerums, George
Hovind, Peter
MacIsaac, Richard J.
Mischak, Harald
Nielsen, Stine E.
Panagiotopoulos, Sianna
Persson, Frederik
Rossing, Peter
author_sort Zürbig, Petra
collection PubMed
description Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing/preventing the need for renal replacement therapy. We evaluated urinary proteome analysis as a tool for prediction of DN. Capillary electrophoresis–coupled mass spectrometry was used to profile the low–molecular weight proteome in urine. We examined urine samples from a longitudinal cohort of type 1 and 2 diabetic patients (n = 35) using a previously generated chronic kidney disease (CKD) biomarker classifier to assess peptides of collected urines for signs of DN. The application of this classifier to samples of normoalbuminuric subjects up to 5 years prior to development of macroalbuminuria enabled early detection of subsequent progression to macroalbuminuria (area under the curve [AUC] 0.93) compared with urinary albumin routinely used to determine the diagnosis (AUC 0.67). Statistical analysis of each urinary CKD biomarker depicted its regulation with respect to diagnosis of DN over time. Collagen fragments were prominent biomarkers 3–5 years before onset of macroalbuminuria. Before albumin excretion starts to increase, there is a decrease in collagen fragments. Urinary proteomics enables noninvasive assessment of DN risk at an early stage via determination of specific collagen fragments.
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spelling pubmed-35018782013-12-01 Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy Zürbig, Petra Jerums, George Hovind, Peter MacIsaac, Richard J. Mischak, Harald Nielsen, Stine E. Panagiotopoulos, Sianna Persson, Frederik Rossing, Peter Diabetes Genetics/Genomes/Proteomics/Metabolomics Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing/preventing the need for renal replacement therapy. We evaluated urinary proteome analysis as a tool for prediction of DN. Capillary electrophoresis–coupled mass spectrometry was used to profile the low–molecular weight proteome in urine. We examined urine samples from a longitudinal cohort of type 1 and 2 diabetic patients (n = 35) using a previously generated chronic kidney disease (CKD) biomarker classifier to assess peptides of collected urines for signs of DN. The application of this classifier to samples of normoalbuminuric subjects up to 5 years prior to development of macroalbuminuria enabled early detection of subsequent progression to macroalbuminuria (area under the curve [AUC] 0.93) compared with urinary albumin routinely used to determine the diagnosis (AUC 0.67). Statistical analysis of each urinary CKD biomarker depicted its regulation with respect to diagnosis of DN over time. Collagen fragments were prominent biomarkers 3–5 years before onset of macroalbuminuria. Before albumin excretion starts to increase, there is a decrease in collagen fragments. Urinary proteomics enables noninvasive assessment of DN risk at an early stage via determination of specific collagen fragments. American Diabetes Association 2012-12 2012-11-15 /pmc/articles/PMC3501878/ /pubmed/22872235 http://dx.doi.org/10.2337/db12-0348 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Zürbig, Petra
Jerums, George
Hovind, Peter
MacIsaac, Richard J.
Mischak, Harald
Nielsen, Stine E.
Panagiotopoulos, Sianna
Persson, Frederik
Rossing, Peter
Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy
title Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy
title_full Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy
title_fullStr Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy
title_full_unstemmed Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy
title_short Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy
title_sort urinary proteomics for early diagnosis in diabetic nephropathy
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501878/
https://www.ncbi.nlm.nih.gov/pubmed/22872235
http://dx.doi.org/10.2337/db12-0348
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