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Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes

OBJECTIVE: We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: Using targeted mass spectrometry, we quantified urinary abundance...

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Autores principales: Vaisar, Tomas, Durbin-Johnson, Blythe, Whitlock, Kathryn, Babenko, Ilona, Mehrotra, Rajnish, Rocke, David M., Afkarian, Maryam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196831/
https://www.ncbi.nlm.nih.gov/pubmed/30150236
http://dx.doi.org/10.2337/dc18-0699
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author Vaisar, Tomas
Durbin-Johnson, Blythe
Whitlock, Kathryn
Babenko, Ilona
Mehrotra, Rajnish
Rocke, David M.
Afkarian, Maryam
author_facet Vaisar, Tomas
Durbin-Johnson, Blythe
Whitlock, Kathryn
Babenko, Ilona
Mehrotra, Rajnish
Rocke, David M.
Afkarian, Maryam
author_sort Vaisar, Tomas
collection PubMed
description OBJECTIVE: We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: Using targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses. RESULTS: At baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m(2) and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29–0.87]) and death (HR [95% CI] 0.56 [0.34–0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41–0.79] and 0.66 [0.44–0.97], respectively); higher urine factor H–related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05–2.48]) in fully adjusted models. CONCLUSIONS: In a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death.
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spelling pubmed-61968312019-11-01 Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes Vaisar, Tomas Durbin-Johnson, Blythe Whitlock, Kathryn Babenko, Ilona Mehrotra, Rajnish Rocke, David M. Afkarian, Maryam Diabetes Care Pathophysiology/Complications OBJECTIVE: We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: Using targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses. RESULTS: At baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m(2) and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29–0.87]) and death (HR [95% CI] 0.56 [0.34–0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41–0.79] and 0.66 [0.44–0.97], respectively); higher urine factor H–related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05–2.48]) in fully adjusted models. CONCLUSIONS: In a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death. American Diabetes Association 2018-11 2018-08-27 /pmc/articles/PMC6196831/ /pubmed/30150236 http://dx.doi.org/10.2337/dc18-0699 Text en © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders 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. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Pathophysiology/Complications
Vaisar, Tomas
Durbin-Johnson, Blythe
Whitlock, Kathryn
Babenko, Ilona
Mehrotra, Rajnish
Rocke, David M.
Afkarian, Maryam
Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes
title Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes
title_full Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes
title_fullStr Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes
title_full_unstemmed Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes
title_short Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes
title_sort urine complement proteins and the risk of kidney disease progression and mortality in type 2 diabetes
topic Pathophysiology/Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196831/
https://www.ncbi.nlm.nih.gov/pubmed/30150236
http://dx.doi.org/10.2337/dc18-0699
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