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Cardiorenal Med. 2015 Oct;5(4):278-88. doi: 10.1159/000435863. Epub 2015 Jul 31.

Soluble Tumor Necrosis Factor Receptor 1 Is Associated with Glomerular Filtration Rate Progression and Incidence of Chronic Kidney Disease in Two Community-Based Cohorts of Elderly Individuals.

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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.
Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Section of Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Cardiovascular Epidemiology, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden ; School of Health and Social Studies, Dalarna University, Falun, Sweden.



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.


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).


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.


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.


Albumin/creatinine ratio; Chronic kidney disease; Community; Glomerular filtration; Inflammation; TNF-α

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