A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease

Rajiv Agarwal, Kevin L. Duffin, Dennis A. Laska, James R. Voelker, Matthew D. Breyer, Peter G. Mitchell

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

BACKGROUND: Diabetic nephropathy imposes a substantial cardiovascular and renal burden contributing to both morbidity and excess mortality. Progression of chronic kidney disease (CKD) in diabetes mellitus is variable, and few biomarkers are available to predict progression accurately. Identification of novel predictive biomarkers may inform clinical care and assist in the design of clinical trials. We hypothesized that urinary and plasma protein biomarkers predict CKD progression independently of the known clinical markers such as albuminuria and estimated glomerular filtration rate (eGFR) in diabetic nephropathy.

METHODS: We studied 67 US veterans with CKD due to type 2 diabetes mellitus and 20 age-matched controls (no CKD, hypertension or cardiovascular disease). After clinical evaluation and the collection of blood and urine specimens for 24 biomarkers, we followed subjects prospectively for the next 2-6 years. CKD progression was defined in three ways: (i) clinically by examining eGFR versus time plots for each individual (slope progression), (ii) progression to end-stage renal disease (ESRD) and (iii) a composite outcome of ESRD or death.

RESULTS: Among 17 urinary and 7 plasma biomarkers evaluated, the relationship of the biomarkers with outcome was as follows: (i) for progression identified by eGFR plots, urinary C-terminal fibroblast growth factor (FGF)-23 emerged to have the strongest primary association (adjusted odds ratio [aOR] 2.08, P = 0.008); (ii) for ESRD, plasma vascular endothelial growth factor (VEGF) had an association (aOR: 1.44, P = 0.027) and (iii) for the composite outcome of death and ESRD, plasma C-terminal FGF-23 also had a robust direct association (aOR: 3.07, P = 0.008).

CONCLUSION: The relationship of biomarkers with future progression of CKD is complex and depends in part on how CKD progression is defined. Biomarkers in the FGF-23 and VEGF-A pathways predicted patient progression independently of albuminuria levels in this patient cohort. Additional studies in other cohorts will help further validate this pilot study.

Original languageEnglish (US)
Pages (from-to)2293-2302
Number of pages10
JournalNephrology Dialysis Transplantation
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2014

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Diabetic Nephropathies
Chronic Renal Insufficiency
Biomarkers
Prospective Studies
Proteins
Chronic Kidney Failure
Glomerular Filtration Rate
Disease Progression
Albuminuria
Odds Ratio
Vascular Endothelial Growth Factor A
Blood Specimen Collection
Urine Specimen Collection
Veterans
Type 2 Diabetes Mellitus
Blood Proteins
Diabetes Mellitus
Cardiovascular Diseases
Clinical Trials
Hypertension

Keywords

  • albuminuria
  • biomarkers
  • chronic kidney disease

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease. / Agarwal, Rajiv; Duffin, Kevin L.; Laska, Dennis A.; Voelker, James R.; Breyer, Matthew D.; Mitchell, Peter G.

In: Nephrology Dialysis Transplantation, Vol. 29, No. 12, 01.12.2014, p. 2293-2302.

Research output: Contribution to journalArticle

Agarwal, Rajiv ; Duffin, Kevin L. ; Laska, Dennis A. ; Voelker, James R. ; Breyer, Matthew D. ; Mitchell, Peter G. / A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 12. pp. 2293-2302.
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N2 - BACKGROUND: Diabetic nephropathy imposes a substantial cardiovascular and renal burden contributing to both morbidity and excess mortality. Progression of chronic kidney disease (CKD) in diabetes mellitus is variable, and few biomarkers are available to predict progression accurately. Identification of novel predictive biomarkers may inform clinical care and assist in the design of clinical trials. We hypothesized that urinary and plasma protein biomarkers predict CKD progression independently of the known clinical markers such as albuminuria and estimated glomerular filtration rate (eGFR) in diabetic nephropathy.METHODS: We studied 67 US veterans with CKD due to type 2 diabetes mellitus and 20 age-matched controls (no CKD, hypertension or cardiovascular disease). After clinical evaluation and the collection of blood and urine specimens for 24 biomarkers, we followed subjects prospectively for the next 2-6 years. CKD progression was defined in three ways: (i) clinically by examining eGFR versus time plots for each individual (slope progression), (ii) progression to end-stage renal disease (ESRD) and (iii) a composite outcome of ESRD or death.RESULTS: Among 17 urinary and 7 plasma biomarkers evaluated, the relationship of the biomarkers with outcome was as follows: (i) for progression identified by eGFR plots, urinary C-terminal fibroblast growth factor (FGF)-23 emerged to have the strongest primary association (adjusted odds ratio [aOR] 2.08, P = 0.008); (ii) for ESRD, plasma vascular endothelial growth factor (VEGF) had an association (aOR: 1.44, P = 0.027) and (iii) for the composite outcome of death and ESRD, plasma C-terminal FGF-23 also had a robust direct association (aOR: 3.07, P = 0.008).CONCLUSION: The relationship of biomarkers with future progression of CKD is complex and depends in part on how CKD progression is defined. Biomarkers in the FGF-23 and VEGF-A pathways predicted patient progression independently of albuminuria levels in this patient cohort. Additional studies in other cohorts will help further validate this pilot study.

AB - BACKGROUND: Diabetic nephropathy imposes a substantial cardiovascular and renal burden contributing to both morbidity and excess mortality. Progression of chronic kidney disease (CKD) in diabetes mellitus is variable, and few biomarkers are available to predict progression accurately. Identification of novel predictive biomarkers may inform clinical care and assist in the design of clinical trials. We hypothesized that urinary and plasma protein biomarkers predict CKD progression independently of the known clinical markers such as albuminuria and estimated glomerular filtration rate (eGFR) in diabetic nephropathy.METHODS: We studied 67 US veterans with CKD due to type 2 diabetes mellitus and 20 age-matched controls (no CKD, hypertension or cardiovascular disease). After clinical evaluation and the collection of blood and urine specimens for 24 biomarkers, we followed subjects prospectively for the next 2-6 years. CKD progression was defined in three ways: (i) clinically by examining eGFR versus time plots for each individual (slope progression), (ii) progression to end-stage renal disease (ESRD) and (iii) a composite outcome of ESRD or death.RESULTS: Among 17 urinary and 7 plasma biomarkers evaluated, the relationship of the biomarkers with outcome was as follows: (i) for progression identified by eGFR plots, urinary C-terminal fibroblast growth factor (FGF)-23 emerged to have the strongest primary association (adjusted odds ratio [aOR] 2.08, P = 0.008); (ii) for ESRD, plasma vascular endothelial growth factor (VEGF) had an association (aOR: 1.44, P = 0.027) and (iii) for the composite outcome of death and ESRD, plasma C-terminal FGF-23 also had a robust direct association (aOR: 3.07, P = 0.008).CONCLUSION: The relationship of biomarkers with future progression of CKD is complex and depends in part on how CKD progression is defined. Biomarkers in the FGF-23 and VEGF-A pathways predicted patient progression independently of albuminuria levels in this patient cohort. Additional studies in other cohorts will help further validate this pilot study.

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