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A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes

Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independen... Full description

Journal Title: Nature medicine 2019-05, Vol.25 (5), p.805-813
Main Author: Niewczas, Monika A
Other Authors: Pavkov, Meda E , Skupien, Jan , Smiles, Adam , Md Dom, Zaipul I , Wilson, Jonathan M , Park, Jihwan , Nair, Viji , Schlafly, Andrew , Saulnier, Pierre-Jean , Satake, Eiichiro , Simeone, Christopher A , Shah, Hetal , Qiu, Chengxiang , Looker, Helen C , Fiorina, Paolo , Ware, Carl F , Sun, Jennifer K , Doria, Alessandro , Kretzler, Matthias , Susztak, Katalin , Duffin, Kevin L , Nelson, Robert G , Krolewski, Andrzej S
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/31011203
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title: A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
format: Article
creator:
  • Niewczas, Monika A
  • Pavkov, Meda E
  • Skupien, Jan
  • Smiles, Adam
  • Md Dom, Zaipul I
  • Wilson, Jonathan M
  • Park, Jihwan
  • Nair, Viji
  • Schlafly, Andrew
  • Saulnier, Pierre-Jean
  • Satake, Eiichiro
  • Simeone, Christopher A
  • Shah, Hetal
  • Qiu, Chengxiang
  • Looker, Helen C
  • Fiorina, Paolo
  • Ware, Carl F
  • Sun, Jennifer K
  • Doria, Alessandro
  • Kretzler, Matthias
  • Susztak, Katalin
  • Duffin, Kevin L
  • Nelson, Robert G
  • Krolewski, Andrzej S
subjects:
  • Adult
  • Aged
  • Article
  • Biomarkers
  • Biomarkers - blood
  • Blood Proteins - genetics
  • Blood Proteins - metabolism
  • Chronic kidney failure
  • Cohort Studies
  • Complications and side effects
  • Cytokine receptors
  • Development and progression
  • Developmental stages
  • Diabetes
  • Diabetes mellitus
  • Diabetes mellitus (insulin dependent)
  • Diabetes mellitus (non-insulin dependent)
  • Diabetes Mellitus, Type 1 - blood
  • Diabetes Mellitus, Type 1 - complications
  • Diabetes Mellitus, Type 1 - genetics
  • Diabetes Mellitus, Type 2 - blood
  • Diabetes Mellitus, Type 2 - complications
  • Diabetes Mellitus, Type 2 - genetics
  • Diabetic Nephropathies - blood
  • Diabetic Nephropathies - etiology
  • Diabetic Nephropathies - genetics
  • Disease Progression
  • End-stage renal disease
  • Female
  • Health aspects
  • Health risks
  • Humans
  • Inflammation
  • Inflammation Mediators - blood
  • Kidney diseases
  • Kidney Failure, Chronic - blood
  • Kidney Failure, Chronic - etiology
  • Kidney Failure, Chronic - genetics
  • Kidneys
  • Male
  • Medical treatment
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Proteins
  • Proteomics
  • Receptors, Tumor Necrosis Factor - blood
  • Receptors, Tumor Necrosis Factor - genetics
  • Risk
  • Risk Factors
  • Therapeutic applications
  • Tumor necrosis factor
ispartof: Nature medicine, 2019-05, Vol.25 (5), p.805-813
description: Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleA signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
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creatorcontribNiewczas, Monika A ; Pavkov, Meda E ; Skupien, Jan ; Smiles, Adam ; Md Dom, Zaipul I ; Wilson, Jonathan M ; Park, Jihwan ; Nair, Viji ; Schlafly, Andrew ; Saulnier, Pierre-Jean ; Satake, Eiichiro ; Simeone, Christopher A ; Shah, Hetal ; Qiu, Chengxiang ; Looker, Helen C ; Fiorina, Paolo ; Ware, Carl F ; Sun, Jennifer K ; Doria, Alessandro ; Kretzler, Matthias ; Susztak, Katalin ; Duffin, Kevin L ; Nelson, Robert G ; Krolewski, Andrzej S
descriptionChronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
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subjectAdult ; Aged ; Article ; Biomarkers ; Biomarkers - blood ; Blood Proteins - genetics ; Blood Proteins - metabolism ; Chronic kidney failure ; Cohort Studies ; Complications and side effects ; Cytokine receptors ; Development and progression ; Developmental stages ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (insulin dependent) ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - complications ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - genetics ; Diabetic Nephropathies - blood ; Diabetic Nephropathies - etiology ; Diabetic Nephropathies - genetics ; Disease Progression ; End-stage renal disease ; Female ; Health aspects ; Health risks ; Humans ; Inflammation ; Inflammation Mediators - blood ; Kidney diseases ; Kidney Failure, Chronic - blood ; Kidney Failure, Chronic - etiology ; Kidney Failure, Chronic - genetics ; Kidneys ; Male ; Medical treatment ; Middle Aged ; Prognosis ; Prospective Studies ; Proteins ; Proteomics ; Receptors, Tumor Necrosis Factor - blood ; Receptors, Tumor Necrosis Factor - genetics ; Risk ; Risk Factors ; Therapeutic applications ; Tumor necrosis factor
ispartofNature medicine, 2019-05, Vol.25 (5), p.805-813
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18Doria, Alessandro
19Kretzler, Matthias
20Susztak, Katalin
21Duffin, Kevin L
22Nelson, Robert G
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descriptionChronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
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16Diabetes mellitus (non-insulin dependent)
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19Diabetes Mellitus, Type 1 - genetics
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titleA signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
authorNiewczas, Monika A ; Pavkov, Meda E ; Skupien, Jan ; Smiles, Adam ; Md Dom, Zaipul I ; Wilson, Jonathan M ; Park, Jihwan ; Nair, Viji ; Schlafly, Andrew ; Saulnier, Pierre-Jean ; Satake, Eiichiro ; Simeone, Christopher A ; Shah, Hetal ; Qiu, Chengxiang ; Looker, Helen C ; Fiorina, Paolo ; Ware, Carl F ; Sun, Jennifer K ; Doria, Alessandro ; Kretzler, Matthias ; Susztak, Katalin ; Duffin, Kevin L ; Nelson, Robert G ; Krolewski, Andrzej S
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50Therapeutic applications
51Tumor necrosis factor
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notesAuthor Contributions: M.A.N. contributed to the design of the study, supervised proteomics data collection, conducted the data analysis, interpreted the results and wrote the manuscript. J.K.S, A.S. A.S., E.S. and C.A.S. were involved in data collection, data management of the Joslin Kidney Study, performed preliminary data analyses and reviewed the manuscript. A.D., Z.I.M.D, H.S. and J.K.S. designed the Joslin study on retinopathy, contributed to eye data collection and analysis, edited and reviewed the manuscript. R.G.N., M.E.P., P.-J.S. and H.C.L. were responsible for design and implementation of the Pima Indian Study, contributed to the proteomic data collection in the Pima Indian Study, performed preliminary data analysis, and reviewed and edited the manuscript. M.K., V.N. and R.G.N. designed the expression study in Pima Indians, provided data analysis, reviewed the manuscript. J.P., C.Q. and K.S. designed the expression study (1KGP) to be used in the current study, performed the data analyses and interpreted the results and edited the manuscript. P.F. and C.F.W. were involved in the interpretation of the results of the study and edited the manuscript. K.L.D. and J.M.W. provided the samples from the baricitinib study, facilitated measurements on the Olink platform, reviewed the analysis, reviewed and edited the manuscript. A.S.K designed the whole study, supervised all aspects of the study implementation, planned and contributed the data analysis, interpreted the data, and contributed to the manuscript writing. M.A.N. and A.S.K. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of data and the accuracy of the data analysis.
abstractChronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
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