PURPOSE: The application of proteomics in chronic kidney disease (CKD) can potentially uncover biomarkers and pathways that are predictive of disease. EXPERIMENTAL DESIGN: Within this context, this study examines the relationship between the human plasma proteome and glomerular filtration rate (GFR) as measured by iohexol clearance in a cohort from Sweden (n = 389; GFR range: 8-100 mL min-1 /1.73 m2 ). A total of 2893 proteins are quantified using a modified aptamer assay. RESULTS: A large proportion of the proteome is associated with GFR, reinforcing the concept that CKD affects multiple physiological systems (individual protein-GFR correlations listed here). Of these, cystatin C shows the most significant correlation with GFR (rho = -0.85, p = 1.2 × 10-97 ), establishing strong validation for the use of this biomarker in CKD diagnostics. Among the other highly significant protein markers are insulin-like growth factor-binding protein 6, neuroblastoma suppressor of tumorigenicity 1, follistatin-related protein 3, trefoil factor 3, and beta-2 microglobulin. These proteins may indicate an imbalance in homeostasis across a variety of cellular processes, which may be underlying renal dysfunction. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, this study represents the most extensive characterization of the plasma proteome and its relation to GFR to date, and suggests the diagnostic and prognostic value of proteomics for CKD across all stages.
PURPOSE: The application of proteomics in chronic kidney disease (CKD) can potentially uncover biomarkers and pathways that are predictive of disease. EXPERIMENTAL DESIGN: Within this context, this study examines the relationship between the human plasma proteome and glomerular filtration rate (GFR) as measured by iohexol clearance in a cohort from Sweden (n = 389; GFR range: 8-100 mL min-1 /1.73 m2 ). A total of 2893 proteins are quantified using a modified aptamer assay. RESULTS: A large proportion of the proteome is associated with GFR, reinforcing the concept that CKD affects multiple physiological systems (individual protein-GFR correlations listed here). Of these, cystatin C shows the most significant correlation with GFR (rho = -0.85, p = 1.2 × 10-97 ), establishing strong validation for the use of this biomarker in CKD diagnostics. Among the other highly significant protein markers are insulin-like growth factor-binding protein 6, neuroblastoma suppressor of tumorigenicity 1, follistatin-related protein 3, trefoil factor 3, and beta-2 microglobulin. These proteins may indicate an imbalance in homeostasis across a variety of cellular processes, which may be underlying renal dysfunction. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, this study represents the most extensive characterization of the plasma proteome and its relation to GFR to date, and suggests the diagnostic and prognostic value of proteomics for CKD across all stages.
Authors: Laura M Raffield; Hong Dang; Katherine A Pratte; Sean Jacobson; Lucas A Gillenwater; Elizabeth Ampleford; Igor Barjaktarevic; Patricia Basta; Clary B Clish; Alejandro P Comellas; Elaine Cornell; Jeffrey L Curtis; Claire Doerschuk; Peter Durda; Claire Emson; Christine M Freeman; Xiuqing Guo; Annette T Hastie; Gregory A Hawkins; Julio Herrera; W Craig Johnson; Wassim W Labaki; Yongmei Liu; Brett Masters; Michael Miller; Victor E Ortega; George Papanicolaou; Stephen Peters; Kent D Taylor; Stephen S Rich; Jerome I Rotter; Paul Auer; Alex P Reiner; Russell P Tracy; Debby Ngo; Robert E Gerszten; Wanda K O'Neal; Russell P Bowler Journal: Proteomics Date: 2020-06 Impact factor: 3.984
Authors: Jack Gisby; Candice L Clarke; Nicholas Medjeral-Thomas; Michelle Willicombe; David C Thomas; James E Peters; Talat H Malik; Artemis Papadaki; Paige M Mortimer; Norzawani B Buang; Shanice Lewis; Marie Pereira; Frederic Toulza; Ester Fagnano; Marie-Anne Mawhin; Emma E Dutton; Lunnathaya Tapeng; Arianne C Richard; Paul Dw Kirk; Jacques Behmoaras; Eleanor Sandhu; Stephen P McAdoo; Maria F Prendecki; Matthew C Pickering; Marina Botto Journal: Elife Date: 2021-03-11 Impact factor: 8.713
Authors: Pamela Matías-García; Rory Wilson; Qi Guo; Shaza Zaghlool; James Eales; Xiaoguang Xu; Fadi Charchar; John Dormer; Haifa Maalmi; Pascal Schlosser; Mohamed Elhadad; Jana Nano; Sapna Sharma; Annette Peters; Alessia Fornoni; Dennis Mook-Kanamori; Juliane Winkelmann; John Danesh; Emanuele Di Angelantonio; Willem Ouwehand; Nicholas Watkins; David Roberts; Agnese Petrera; Johannes Graumann; Wolfgang Koenig; Kristian Hveem; Christian Jonasson; Anna Köttgen; Adam Butterworth; Marco Prunotto; Stefanie Hauck; Christian Herder; Karsten Suhre; Christian Gieger; Maciej Tomaszewski; Alexander Teumer; Melanie Waldenberger Journal: J Am Soc Nephrol Date: 2021-06-16 Impact factor: 14.978
Authors: Adrienne Tin; Keenan A Walker; Jan Bressler; B Gwen Windham; Michael Griswold; Kevin Sullivan; Aozhou Wu; Rebecca Gottesman; Myriam Fornage; Josef Coresh; A Richey Sharrett; Aaron R Folsom; Thomas H Mosley Journal: Neuroepidemiology Date: 2021-06-02 Impact factor: 5.393
Authors: Markus Sällman Almén; Jonas Björk; Ulf Nyman; Veronica Lindström; Magnus Jonsson; Magnus Abrahamson; AnnaLotta Schiller Vestergren; Örjan Lindhe; Gary Franklin; Anders Christensson; Anders Grubb Journal: Kidney Int Rep Date: 2018-09-13