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. Published by Oxford University Press on behalf of ERA-EDTA 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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. Published by Oxford University Press on behalf of ERA-EDTA 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Authors: Juan Jesús Carrero; Morgan E Grams; Yingying Sang; Johan Ärnlöv; Alessandro Gasparini; Kunihiro Matsushita; Abdul R Qureshi; Marie Evans; Peter Barany; Bengt Lindholm; Shoshana H Ballew; Andrew S Levey; Ron T Gansevoort; Carl G Elinder; Josef Coresh Journal: Kidney Int Date: 2016-12-04 Impact factor: 10.612
Authors: Sherry G Mansour; William R Zhang; Dennis G Moledina; Steven G Coca; Yaqi Jia; Heather Thiessen-Philbrook; Eric McArthur; Kazunori Inoue; Jay L Koyner; Michael G Shlipak; F Perry Wilson; Amit X Garg; Shuta Ishibe; Chirag R Parikh Journal: Am J Kidney Dis Date: 2019-04-05 Impact factor: 8.860
Authors: Maryam Afkarian; Leila R Zelnick; John Ruzinski; Bryan Kestenbaum; Jonathan Himmelfarb; Ian H de Boer; Rajnish Mehrotra Journal: J Diabetes Complications Date: 2015-09-02 Impact factor: 2.852
Authors: Michelle J Pena; Andreas Heinzel; Georg Heinze; Alaa Alkhalaf; Stephan J L Bakker; Tri Q Nguyen; Roel Goldschmeding; Henk J G Bilo; Paul Perco; Bernd Mayer; Dick de Zeeuw; Hiddo J Lambers Heerspink Journal: PLoS One Date: 2015-05-14 Impact factor: 3.240