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Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine

Sundin, Per-Ola ; Sjöström, Per ; Jones, Ian ; Olsson, Lovisa A ; Udumyan, Ruzan ; Grubb, Anders LU orcid ; Lindström, Veronica LU orcid and Montgomery, Scott (2017) In Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 32(4). p.663-670
Abstract

Background: Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.

Methods: Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred... (More)

Background: Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.

Methods: Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol.

Results: Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model.

Conclusions: Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers/blood, Comorbidity, Creatinine/blood, Cystatin C/blood, Female, Glomerular Filtration Rate, Humans, Iohexol/analysis, Kidney Diseases/blood, Male, Middle Aged, Models, Statistical, Survival Rate, Young Adult
in
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
volume
32
issue
4
pages
663 - 670
publisher
Oxford University Press
external identifiers
  • pmid:28340079
  • scopus:85019091905
ISSN
1460-2385
DOI
10.1093/ndt/gfx004
language
English
LU publication?
no
additional info
© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
id
6647a3c2-dec7-49aa-97a1-b29c45fe33a3
date added to LUP
2021-11-03 07:45:46
date last changed
2024-05-04 16:19:29
@article{6647a3c2-dec7-49aa-97a1-b29c45fe33a3,
  abstract     = {{<p>Background: Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.</p><p>Methods: Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol.</p><p>Results: Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model.</p><p>Conclusions: Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.</p>}},
  author       = {{Sundin, Per-Ola and Sjöström, Per and Jones, Ian and Olsson, Lovisa A and Udumyan, Ruzan and Grubb, Anders and Lindström, Veronica and Montgomery, Scott}},
  issn         = {{1460-2385}},
  keywords     = {{Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers/blood; Comorbidity; Creatinine/blood; Cystatin C/blood; Female; Glomerular Filtration Rate; Humans; Iohexol/analysis; Kidney Diseases/blood; Male; Middle Aged; Models, Statistical; Survival Rate; Young Adult}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{663--670}},
  publisher    = {{Oxford University Press}},
  series       = {{Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}},
  title        = {{Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine}},
  url          = {{http://dx.doi.org/10.1093/ndt/gfx004}},
  doi          = {{10.1093/ndt/gfx004}},
  volume       = {{32}},
  year         = {{2017}},
}