Meyeon Park1, Daniela Maristany2, Debbie Huang3, Michael G Shlipak4, Mary Whooley4. 1. Division of Nephrology, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: meyeon.park@ucsf.edu. 2. School of Medicine, University of California, San Francisco, San Francisco, CA, USA. 3. Division of Nephrology, University of California, San Francisco, San Francisco, CA, USA. 4. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Abstract
BACKGROUND AND AIMS: Tumor necrosis factor receptor type 1 (TNFR1) is associated with kidney disease and mortality risk in various populations. Whether or not kidney function mediates mortality risk is unknown. We evaluated associations of TNFR1 levels with measures of kidney function, cardiovascular events, and mortality in a population of veterans with stable ischemic heart disease. METHODS: TNFR1 was measured from baseline serum samples in the Heart and Soul Study; elevated levels were defined by the highest quartile (Q4, >3.4 ng/ml). We evaluated associations of high TNFR1 with baseline estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) and with longitudinal changes in eGFR (rapid loss), as well as with incident myocardial infarction (MI), heart failure hospitalizations (HF), and mortality over a median follow-up time of 8.9 years. Covariates included demographics and comorbid conditions. RESULTS: Among 985 participants who had TNFR1 measurements, median TNFR1 was 2.33 ng/ml (IQR 1.8-3.1). Relative to Q1, Q4 had higher risk of eGFR <60 ml/min/1.73 m2 (RR 11.71 [95% CI 5.46, 25.11]); ACR ≥ 30 mg/g (2.44 [1.15, 5.19]); and rapid loss in kidney function (2.10 [1.12, 3.92]). Although TNFR1 Q4 was associated with MI, HF, and mortality after demographic adjustment, there were no associations in fully-adjusted models (1.04 [0.44, 2.49]; 1.02 [0.48, 2.15]; 1.42 [0.88, 2.28], respectively). CONCLUSIONS: Levels of TNFR1 are associated longitudinally with kidney function decline but not with MI, HF or mortality risk after adjustment. Kidney disease may mediate the risk of MI, HF, and mortality associated with TNFR1.
BACKGROUND AND AIMS: Tumor necrosis factor receptor type 1 (TNFR1) is associated with kidney disease and mortality risk in various populations. Whether or not kidney function mediates mortality risk is unknown. We evaluated associations of TNFR1 levels with measures of kidney function, cardiovascular events, and mortality in a population of veterans with stable ischemic heart disease. METHODS:TNFR1 was measured from baseline serum samples in the Heart and Soul Study; elevated levels were defined by the highest quartile (Q4, >3.4 ng/ml). We evaluated associations of high TNFR1 with baseline estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) and with longitudinal changes in eGFR (rapid loss), as well as with incident myocardial infarction (MI), heart failure hospitalizations (HF), and mortality over a median follow-up time of 8.9 years. Covariates included demographics and comorbid conditions. RESULTS: Among 985 participants who had TNFR1 measurements, median TNFR1 was 2.33 ng/ml (IQR 1.8-3.1). Relative to Q1, Q4 had higher risk of eGFR <60 ml/min/1.73 m2 (RR 11.71 [95% CI 5.46, 25.11]); ACR ≥ 30 mg/g (2.44 [1.15, 5.19]); and rapid loss in kidney function (2.10 [1.12, 3.92]). Although TNFR1 Q4 was associated with MI, HF, and mortality after demographic adjustment, there were no associations in fully-adjusted models (1.04 [0.44, 2.49]; 1.02 [0.48, 2.15]; 1.42 [0.88, 2.28], respectively). CONCLUSIONS: Levels of TNFR1 are associated longitudinally with kidney function decline but not with MI, HF or mortality risk after adjustment. Kidney disease may mediate the risk of MI, HF, and mortality associated with TNFR1.
Authors: Russell V Luepker; Fred S Apple; Robert H Christenson; Richard S Crow; Stephen P Fortmann; David Goff; Robert J Goldberg; Mary M Hand; Allan S Jaffe; Desmond G Julian; Daniel Levy; Teri Manolio; Shanthi Mendis; George Mensah; Andrzej Pajak; Ronald J Prineas; K Srinath Reddy; Veronique L Roger; Wayne D Rosamond; Eyal Shahar; A Richey Sharrett; Paul Sorlie; Hugh Tunstall-Pedoe Journal: Circulation Date: 2003-11-10 Impact factor: 29.690
Authors: Monika A Niewczas; Tomohito Gohda; Jan Skupien; Adam M Smiles; William H Walker; Florencia Rosetti; Xavier Cullere; John H Eckfeldt; Alessandro Doria; Tanya N Mayadas; James H Warram; Andrzej S Krolewski Journal: J Am Soc Nephrol Date: 2012-01-19 Impact factor: 10.121
Authors: Kirsten Bibbins-Domingo; Reena Gupta; Beeya Na; Alan H B Wu; Nelson B Schiller; Mary A Whooley Journal: JAMA Date: 2007-01-10 Impact factor: 56.272
Authors: Lesley A Inker; Christopher H Schmid; Hocine Tighiouart; John H Eckfeldt; Harold I Feldman; Tom Greene; John W Kusek; Jane Manzi; Frederick Van Lente; Yaping Lucy Zhang; Josef Coresh; Andrew S Levey Journal: N Engl J Med Date: 2012-07-05 Impact factor: 91.245
Authors: Andrew S Levey; Josef Coresh; Ethan Balk; Annamaria T Kausz; Adeera Levin; Michael W Steffes; Ronald J Hogg; Ronald D Perrone; Joseph Lau; Garabed Eknoyan Journal: Ann Intern Med Date: 2003-07-15 Impact factor: 25.391
Authors: Mary A Whooley; Peter de Jonge; Eric Vittinghoff; Christian Otte; Rudolf Moos; Robert M Carney; Sadia Ali; Sunaina Dowray; Beeya Na; Mitchell D Feldman; Nelson B Schiller; Warren S Browner Journal: JAMA Date: 2008-11-26 Impact factor: 56.272
Authors: Ramachandran S Vasan; Lisa M Sullivan; Ronenn Roubenoff; Charles A Dinarello; Tamara Harris; Emelia J Benjamin; Douglas B Sawyer; Daniel Levy; Peter W F Wilson; Ralph B D'Agostino Journal: Circulation Date: 2003-03-25 Impact factor: 29.690
Authors: Taha Sen; Jingwei Li; Brendon L Neuen; Bruce Neal; Clare Arnott; Chirag R Parikh; Steven G Coca; Vlado Perkovic; Kenneth W Mahaffey; Yshai Yavin; Norman Rosenthal; Michael K Hansen; Hiddo J L Heerspink Journal: Diabetologia Date: 2021-08-20 Impact factor: 10.122