Axel C Carlsson1, Lina Nordquist2, Tobias E Larsson3, Juan-Jesús Carrero3, Anders Larsson4, Lars Lind5, Johan Ärnlöv6. 1. Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden ; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden. 2. Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. 3. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. 4. Section of Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. 5. Cardiovascular Epidemiology, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden. 6. Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden ; School of Health and Social Studies, Dalarna University, Falun, Sweden.
Abstract
OBJECTIVE: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes. RESEARCH DESIGN AND METHODS: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as ≥60, 30-60, and <30 ml/min/1.73 m(2). RESULTS: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR ≥60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes. CONCLUSIONS: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.
OBJECTIVE: We aimed to explore and validate the longitudinal associations between soluble tumornecrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes. RESEARCH DESIGN AND METHODS: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as ≥60, 30-60, and <30 ml/min/1.73 m(2). RESULTS: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR ≥60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes. CONCLUSIONS: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.
Authors: Stein I Hallan; Josef Coresh; Brad C Astor; Arne Asberg; Neil R Powe; Solfrid Romundstad; Hans A Hallan; Stian Lydersen; Jostein Holmen Journal: J Am Soc Nephrol Date: 2006-06-21 Impact factor: 10.121
Authors: Dominik N Muller; Erdenechimeg Shagdarsuren; Joon-Keun Park; Ralf Dechend; Eero Mervaala; Franziska Hampich; Anette Fiebeler; Xinsheng Ju; Piet Finckenberg; Jürgen Theuer; Christiane Viedt; Joerg Kreuzer; Harald Heidecke; Hermann Haller; Martin Zenke; Friedrich C Luft Journal: Am J Pathol Date: 2002-11 Impact factor: 4.307
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: Rafia S Al-Lamki; Jun Wang; Peter Vandenabeele; J Andrew Bradley; Sathia Thiru; Dianghong Luo; Wang Min; Jordan S Pober; John R Bradley Journal: FASEB J Date: 2005-10 Impact factor: 5.191
Authors: Jorge M Luna; Yeseon Moon; Khin Liu; Steven Spitalnik; Myunghee Paik; Ralph Sacco; Mitchell S V Elkind Journal: Age Ageing Date: 2013-01-15 Impact factor: 10.668
Authors: Andrzej S Krolewski; Monika A Niewczas; Jan Skupien; Tomhito Gohda; Adam Smiles; Jon H Eckfeldt; Alessandro Doria; James H Warram Journal: Diabetes Care Date: 2013-08-12 Impact factor: 19.112
Authors: Shabnam Salimi; Michelle D Shardell; Stephen L Seliger; Stefania Bandinelli; Jack M Guralnik; Luigi Ferrucci Journal: J Am Geriatr Soc Date: 2018-01-23 Impact factor: 5.562
Authors: Manmeet S Ahluwalia; Stephanie Bou-Anak; Monica E Burgett; Nehaw Sarmey; Divya Khosla; Saurabh Dahiya; Robert J Weil; Eunnyung Bae; Ping Huang; Mary McGraw; Lisa M Grove; Mitchell A Olman; Richard A Prayson; John H Suh; G Yancey Gillespie; Jill Barnholtz-Sloan; Amy S Nowacki; Gene H Barnett; Candece L Gladson Journal: J Neurooncol Date: 2016-11-17 Impact factor: 4.130
Authors: Girish N Nadkarni; Kinsuk Chauhan; Divya A Verghese; Chirag R Parikh; Ron Do; Carol R Horowitz; Erwin P Bottinger; Steven G Coca Journal: Kidney Int Date: 2018-04-25 Impact factor: 10.612
Authors: Kinsuk Chauhan; Girish N Nadkarni; Fergus Fleming; James McCullough; Cijiang J He; John Quackenbush; Barbara Murphy; Michael J Donovan; Steven G Coca; Joseph V Bonventre Journal: Kidney360 Date: 2020-06-30
Authors: Richard L Amdur; Harold I Feldman; Jayanta Gupta; Wei Yang; Peter Kanetsky; Michael Shlipak; Mahboob Rahman; James P Lash; Raymond R Townsend; Akinlolu Ojo; Akshay Roy-Chaudhury; Alan S Go; Marshall Joffe; Jiang He; Vaidyanathapuram S Balakrishnan; Paul L Kimmel; John W Kusek; Dominic S Raj Journal: Clin J Am Soc Nephrol Date: 2016-06-23 Impact factor: 8.237
Authors: Esmeralda Castillo-Rodríguez; Soledad Pizarro-Sánchez; Ana B Sanz; Adrian M Ramos; Maria Dolores Sanchez-Niño; Catalina Martin-Cleary; Beatriz Fernandez-Fernandez; Alberto Ortiz Journal: Toxins (Basel) Date: 2017-03-23 Impact factor: 4.546