Jørgen Schei1, Vidar T N Stefansson2, Ulla Dorte Mathisen3, Bjørn O Eriksen3, Marit D Solbu3, Trond G Jenssen4, Toralf Melsom3. 1. Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and jorgen.schei@unn.no. 2. Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and. 3. Section of Nephrology, University Hospital of North Norway, Tromsø, Norway; Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and. 4. Department of Clinical Medicine, Metabolic and Renal Research Group, The Artic University of Norway, Tromsø, Norway; and Department of Nephrology, Oslo University Hospital, Oslo, Norway.
Abstract
BACKGROUND AND OBJECTIVES: eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromsø Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR. RESULTS: sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m(2); 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m(2); 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m(2); 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (-1.4 ml/min per 1.73 m(2); 95% CI, -2.1 to -0.6 per SD increase in sTNFR2, and -0.76 ml/min per 1.73 m(2); 95% CI, -1.4 to -0.1 per SD increase in log CRP). CONCLUSIONS: eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR-related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies.
BACKGROUND AND OBJECTIVES:eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromsø Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR. RESULTS: sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m(2); 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m(2); 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m(2); 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (-1.4 ml/min per 1.73 m(2); 95% CI, -2.1 to -0.6 per SD increase in sTNFR2, and -0.76 ml/min per 1.73 m(2); 95% CI, -1.4 to -0.1 per SD increase in log CRP). CONCLUSIONS: eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR-related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies.
Authors: John Danesh; Sarah Lewington; Simon G Thompson; Gordon D O Lowe; Rory Collins; J B Kostis; A C Wilson; A R Folsom; K Wu; M Benderly; U Goldbourt; J Willeit; S Kiechl; J W G Yarnell; P M Sweetnam; P C Elwood; M Cushman; B M Psaty; R P Tracy; A Tybjaerg-Hansen; F Haverkate; M P M de Maat; F G R Fowkes; A J Lee; F B Smith; V Salomaa; K Harald; R Rasi; E Vahtera; P Jousilahti; J Pekkanen; R D'Agostino; W B Kannel; P W F Wilson; G Tofler; C L Arocha-Piñango; A Rodriguez-Larralde; E Nagy; M Mijares; R Espinosa; E Rodriquez-Roa; E Ryder; M P Diez-Ewald; G Campos; V Fernandez; E Torres; R Marchioli; F Valagussa; A Rosengren; L Wilhelmsen; G Lappas; H Eriksson; P Cremer; D Nagel; J D Curb; B Rodriguez; K Yano; J T Salonen; K Nyyssönen; T-P Tuomainen; B Hedblad; P Lind; H Loewel; W Koenig; T W Meade; J A Cooper; B De Stavola; C Knottenbelt; G J Miller; J A Cooper; K A Bauer; R D Rosenberg; S Sato; A Kitamura; Y Naito; T Palosuo; P Ducimetiere; P Amouyel; D Arveiler; A E Evans; J Ferrieres; I Juhan-Vague; A Bingham; H Schulte; G Assmann; B Cantin; B Lamarche; J-P Després; G R Dagenais; H Tunstall-Pedoe; M Woodward; Y Ben-Shlomo; G Davey Smith; V Palmieri; J L Yeh; A Rudnicka; P Ridker; F Rodeghiero; A Tosetto; J Shepherd; I Ford; M Robertson; E Brunner; M Shipley; E J M Feskens; D Kromhout; A Dickinson; B Ireland; K Juzwishin; S Kaptoge; S Lewington; A Memon; N Sarwar; M Walker; J Wheeler; I White; A Wood Journal: JAMA Date: 2005-10-12 Impact factor: 56.272
Authors: Iris Shai; Matthias B Schulze; Joann E Manson; Kathryn M Rexrode; Meir J Stampfer; Christos Mantzoros; Frank B Hu Journal: Diabetes Care Date: 2005-06 Impact factor: 19.112
Authors: C R Keller; M C Odden; L F Fried; A B Newman; S Angleman; C A Green; S R Cummings; T B Harris; M G Shlipak Journal: Kidney Int Date: 2006-12-20 Impact factor: 10.612
Authors: John Danesh; Jeremy G Wheeler; Gideon M Hirschfield; Shinichi Eda; Gudny Eiriksdottir; Ann Rumley; Gordon D O Lowe; Mark B Pepys; Vilmundur Gudnason Journal: N Engl J Med Date: 2004-04-01 Impact factor: 91.245
Authors: Mehdi H Shishehbor; Leonardo P J Oliveira; Michael S Lauer; Dennis L Sprecher; Kathy Wolski; Leslie Cho; Byron J Hoogwerf; Stanley L Hazen Journal: Am J Cardiol Date: 2008-04-09 Impact factor: 2.778
Authors: Lesley A Stevens; Christopher H Schmid; Tom Greene; Liang Li; Gerald J Beck; Marshall M Joffe; Marc Froissart; John W Kusek; Yaping Lucy Zhang; Josef Coresh; Andrew S Levey Journal: Kidney Int Date: 2008-12-31 Impact factor: 10.612
Authors: Hans Pottel; Pierre Delanaye; Elke Schaeffner; Laurence Dubourg; Bjørn Odvar Eriksen; Toralf Melsom; Edmund J Lamb; Andrew D Rule; Stephen T Turner; Richard J Glassock; Vandréa De Souza; Luciano Selistre; Karolien Goffin; Steven Pauwels; Christophe Mariat; Martin Flamant; Natalie Ebert Journal: Nephrol Dial Transplant Date: 2017-03-01 Impact factor: 5.992
Authors: Emelia J Benjamin; Michael J Blaha; Stephanie E Chiuve; Mary Cushman; Sandeep R Das; Rajat Deo; Sarah D de Ferranti; James Floyd; Myriam Fornage; Cathleen Gillespie; Carmen R Isasi; Monik C Jiménez; Lori Chaffin Jordan; Suzanne E Judd; Daniel Lackland; Judith H Lichtman; Lynda Lisabeth; Simin Liu; Chris T Longenecker; Rachel H Mackey; Kunihiro Matsushita; Dariush Mozaffarian; Michael E Mussolino; Khurram Nasir; Robert W Neumar; Latha Palaniappan; Dilip K Pandey; Ravi R Thiagarajan; Mathew J Reeves; Matthew Ritchey; Carlos J Rodriguez; Gregory A Roth; Wayne D Rosamond; Comilla Sasson; Amytis Towfighi; Connie W Tsao; Melanie B Turner; Salim S Virani; Jenifer H Voeks; Joshua Z Willey; John T Wilkins; Jason Hy Wu; Heather M Alger; Sally S Wong; Paul Muntner Journal: Circulation Date: 2017-01-25 Impact factor: 29.690
Authors: Bjørn O Eriksen; Runolfur Palsson; Natalie Ebert; Toralf Melsom; Markus van der Giet; Vilmundur Gudnason; Olafur S Indridason; Lesley A Inker; Trond G Jenssen; Andrew S Levey; Marit D Solbu; Hocine Tighiouart; Elke Schaeffner Journal: J Am Soc Nephrol Date: 2020-06-04 Impact factor: 10.121
Authors: Johanna Helmersson-Karlqvist; Miklos Lipcsey; Johan Ärnlöv; Max Bell; Bo Ravn; Alain Dardashti; Anders Larsson Journal: Sci Rep Date: 2021-03-15 Impact factor: 4.379