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Association of systemic collagen type IV formation with survival among patients undergoing hemodialysis.

Leeming DJ, Karsdal MA, Rasmussen LM, Scholze A, Tepel M - PLoS ONE (2013)

Bottom Line: Plasma P4NP_7S was analyzed using a specific enzyme-linked immunosorbent assay detecting the amino-terminal propeptide of type IV procollagen.Survival analysis showed an increased risk of death in the highest P4NP_7S category compared to the other categories (Chi square 6.903; P = 0.032).Median survival was only 105 days in the highest P4NP_7S category whereas it was 629 days in the medium category, and 905 days in the lowest category.

View Article: PubMed Central - PubMed

Affiliation: Nordic Bioscience, Herlev, Denmark.

ABSTRACT

Objective: The 7S domain of collagen type IV (P4NP_7S) assessed in plasma represents systemic collagen type IV formation. The objective of the study was to investigate the association of systemic collagen type IV formation with survival among patients undergoing hemodialysis.

Methods: We performed an observational cohort study of 371 hemodialysis patients. Plasma P4NP_7S was analyzed using a specific enzyme-linked immunosorbent assay detecting the amino-terminal propeptide of type IV procollagen. Association between categories of plasma P4NP_7S concentrations and survival was initially assessed by Kaplan-Meier analysis, then in an adjusted Cox model.

Results: For hemodialysis patients in the highest category of systemic collagen type IV formation, i.e. plasma P4NP_7S concentrations more than 775 pg/L, an increased risk for death was observed (highest P4NP_7S category vs all other categories, hazard ratio, 1.934; 95% confidence interval, 1.139 to 3.285). Survival analysis showed an increased risk of death in the highest P4NP_7S category compared to the other categories (Chi square 6.903; P = 0.032). Median survival was only 105 days in the highest P4NP_7S category whereas it was 629 days in the medium category, and 905 days in the lowest category. Multivariable-adjusted Cox regression showed increased odds for death with higher age and higher P4NP_7S categories. Systemic collagen type IV formation was associated with plasma concentrations of the collagen IV degradation product C4M (Spearman r = 0.764; P<0.0001) confirming extracellular matrix turnover.

Conclusion: Among hemodialysis patients elevated systemic collagen type IV formation suggesting accelerating systemic fibrosis was associated with increased risk of death.

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Kaplan-Meier survival curves for death in 371 hemodialysis patients.Patients were stratified according to lowest, medium, and highest categories of the 7S domain of collagen type IV (P4NP_7S) plasma concentration (Log rank test, chi square = 6.90; P = 0.032).
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pone-0071050-g001: Kaplan-Meier survival curves for death in 371 hemodialysis patients.Patients were stratified according to lowest, medium, and highest categories of the 7S domain of collagen type IV (P4NP_7S) plasma concentration (Log rank test, chi square = 6.90; P = 0.032).

Mentions: 182 patients (49%) died during a follow up time of 5 years. Death occurred at a median of 201 days (IQR, 61 to 471 days) after study entry. The causes of death were cardiovascular diseases in 113 patients (62%), infections in 36 patients (20%), cancer in 22 patients (12%), and others/unknown in 11 (6%). In hemodialysis patients with the highest systemic collagen type IV formation an increased risk for death was observed (highest plasma P4NP_7S category vs all other categories, hazard ratio [HR], 1.934; 95% confidence interval [CI], 1.139 to 3.285, Mantel-Haenszel method). Further Kaplan-Meier analysis revealed significant survival differences between hemodialysis patients stratified into plasma P4NP_7S categories. Survival analysis showed an increased risk of death in the highest plasma P4NP_7S category compared to all other categories (Chi square 6.903; P = 0.032 by log-rank test). Median survival was only 105 days in the highest plasma P4NP_7S category, whereas it was 629 days in the medium category, and 905 days in the lowest plasma P4NP_7S category (Figure 1). In hemodialysis patients with the highest systemic collagen type IV formation the causes of death were cardiovascular diseases in 50%, infections in 34%, cancer in 8%, and others/unknown in 8%. Similar results were obtained in subgroups of patients with time since initiation of dialysis less or more than 90 days. In patients with time since initiation of dialysis less than 90 days the median survival was only 362 days in the highest plasma P4NP_7S category, whereas it was 901 days in the lowest plasma P4NP_7S category. In patients with time since initiation of dialysis more than 90 days the median survival was only 176 days in the highest plasma P4NP_7S category, whereas it was 634 days in the lowest plasma P4NP_7S category (Figure 2).


Association of systemic collagen type IV formation with survival among patients undergoing hemodialysis.

Leeming DJ, Karsdal MA, Rasmussen LM, Scholze A, Tepel M - PLoS ONE (2013)

Kaplan-Meier survival curves for death in 371 hemodialysis patients.Patients were stratified according to lowest, medium, and highest categories of the 7S domain of collagen type IV (P4NP_7S) plasma concentration (Log rank test, chi square = 6.90; P = 0.032).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3750054&req=5

pone-0071050-g001: Kaplan-Meier survival curves for death in 371 hemodialysis patients.Patients were stratified according to lowest, medium, and highest categories of the 7S domain of collagen type IV (P4NP_7S) plasma concentration (Log rank test, chi square = 6.90; P = 0.032).
Mentions: 182 patients (49%) died during a follow up time of 5 years. Death occurred at a median of 201 days (IQR, 61 to 471 days) after study entry. The causes of death were cardiovascular diseases in 113 patients (62%), infections in 36 patients (20%), cancer in 22 patients (12%), and others/unknown in 11 (6%). In hemodialysis patients with the highest systemic collagen type IV formation an increased risk for death was observed (highest plasma P4NP_7S category vs all other categories, hazard ratio [HR], 1.934; 95% confidence interval [CI], 1.139 to 3.285, Mantel-Haenszel method). Further Kaplan-Meier analysis revealed significant survival differences between hemodialysis patients stratified into plasma P4NP_7S categories. Survival analysis showed an increased risk of death in the highest plasma P4NP_7S category compared to all other categories (Chi square 6.903; P = 0.032 by log-rank test). Median survival was only 105 days in the highest plasma P4NP_7S category, whereas it was 629 days in the medium category, and 905 days in the lowest plasma P4NP_7S category (Figure 1). In hemodialysis patients with the highest systemic collagen type IV formation the causes of death were cardiovascular diseases in 50%, infections in 34%, cancer in 8%, and others/unknown in 8%. Similar results were obtained in subgroups of patients with time since initiation of dialysis less or more than 90 days. In patients with time since initiation of dialysis less than 90 days the median survival was only 362 days in the highest plasma P4NP_7S category, whereas it was 901 days in the lowest plasma P4NP_7S category. In patients with time since initiation of dialysis more than 90 days the median survival was only 176 days in the highest plasma P4NP_7S category, whereas it was 634 days in the lowest plasma P4NP_7S category (Figure 2).

Bottom Line: Plasma P4NP_7S was analyzed using a specific enzyme-linked immunosorbent assay detecting the amino-terminal propeptide of type IV procollagen.Survival analysis showed an increased risk of death in the highest P4NP_7S category compared to the other categories (Chi square 6.903; P = 0.032).Median survival was only 105 days in the highest P4NP_7S category whereas it was 629 days in the medium category, and 905 days in the lowest category.

View Article: PubMed Central - PubMed

Affiliation: Nordic Bioscience, Herlev, Denmark.

ABSTRACT

Objective: The 7S domain of collagen type IV (P4NP_7S) assessed in plasma represents systemic collagen type IV formation. The objective of the study was to investigate the association of systemic collagen type IV formation with survival among patients undergoing hemodialysis.

Methods: We performed an observational cohort study of 371 hemodialysis patients. Plasma P4NP_7S was analyzed using a specific enzyme-linked immunosorbent assay detecting the amino-terminal propeptide of type IV procollagen. Association between categories of plasma P4NP_7S concentrations and survival was initially assessed by Kaplan-Meier analysis, then in an adjusted Cox model.

Results: For hemodialysis patients in the highest category of systemic collagen type IV formation, i.e. plasma P4NP_7S concentrations more than 775 pg/L, an increased risk for death was observed (highest P4NP_7S category vs all other categories, hazard ratio, 1.934; 95% confidence interval, 1.139 to 3.285). Survival analysis showed an increased risk of death in the highest P4NP_7S category compared to the other categories (Chi square 6.903; P = 0.032). Median survival was only 105 days in the highest P4NP_7S category whereas it was 629 days in the medium category, and 905 days in the lowest category. Multivariable-adjusted Cox regression showed increased odds for death with higher age and higher P4NP_7S categories. Systemic collagen type IV formation was associated with plasma concentrations of the collagen IV degradation product C4M (Spearman r = 0.764; P<0.0001) confirming extracellular matrix turnover.

Conclusion: Among hemodialysis patients elevated systemic collagen type IV formation suggesting accelerating systemic fibrosis was associated with increased risk of death.

Show MeSH
Related in: MedlinePlus