Shabnam Salimi1, Michelle D Shardell2, Stephen L Seliger3, Stefania Bandinelli4, Jack M Guralnik1, Luigi Ferrucci3. 1. Department of Epidemiology and Public Health, School of Medicine, University of Maryland, Baltimore, Maryland. 2. Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland. 3. Division of Nephrology, School of Medicine, University of Maryland, Baltimore, Maryland. 4. Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Florence, Italy.
Abstract
OBJECTIVES: To examine the hypothesis that the inflammatory state of aging is a risk factor for accelerated renal function (RF) decline using inflammatory biomarkers and RF measures collected over 9 years of follow-up in relatively healthy individuals enrolled in the Invecchiare in Chianti study. DESIGN: Longitudinal. SETTING: Community. PARTICIPANTS: Individuals aged 60 and older with baseline estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 and greater and no diabetes mellitus (DM) (N = 687). MEASURES: eGFR, as a proxy for RF, was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and 3-, 6-, and 9-year follow-up. Incident chronic kidney disease (CKD) was defined as new-onset eGFR less than 60 mL/min per 1.73 m2 at each follow-up. Predictors included baseline and time-dependent inflammatory biomarkers: soluble tumor necrosis factor alpha receptors (sTNFα-R1 and -R2), interleukin (IL)-6, IL-18, IL-1β, IL-1 receptor antagonist, and high-sensitivity C-reactive protein. RESULTS: Higher baseline sTNFα-R1 was significantly associated with lower eGFR over 9 years, independent of DM or blood pressure (baseline: β^ = -0.39, P = .001; 3-year: β^ = -0.26, P = .001; 6-year: β^ = -0.36, P = .001; 9-year: β^ = -0.47, P = .001). The rate of TNFα-R1 change was significantly associated with rate of eGFR change (β^ = -0.18, P = .001). Baseline sTNFα-R1 predicted incident CKD (per 1-standard deviation increment: 3-year: relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.1-1.5; 6-year: RR = 1.5, 95% CI = 1.1-2.2; 9-year RR = 1.6, 95% CI = 1.1-2.2). Similar results were found for sTNFα-R2. CONCLUSION: Baseline TNFα-R levels and their rates of change were significantly associated with RF decline and incident CKD in older adults independent of DM or blood pressure.
OBJECTIVES: To examine the hypothesis that the inflammatory state of aging is a risk factor for accelerated renal function (RF) decline using inflammatory biomarkers and RF measures collected over 9 years of follow-up in relatively healthy individuals enrolled in the Invecchiare in Chianti study. DESIGN: Longitudinal. SETTING: Community. PARTICIPANTS: Individuals aged 60 and older with baseline estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 and greater and no diabetes mellitus (DM) (N = 687). MEASURES: eGFR, as a proxy for RF, was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and 3-, 6-, and 9-year follow-up. Incident chronic kidney disease (CKD) was defined as new-onset eGFR less than 60 mL/min per 1.73 m2 at each follow-up. Predictors included baseline and time-dependent inflammatory biomarkers: soluble tumor necrosis factor alpha receptors (sTNFα-R1 and -R2), interleukin (IL)-6, IL-18, IL-1β, IL-1 receptor antagonist, and high-sensitivity C-reactive protein. RESULTS: Higher baseline sTNFα-R1 was significantly associated with lower eGFR over 9 years, independent of DM or blood pressure (baseline: β^ = -0.39, P = .001; 3-year: β^ = -0.26, P = .001; 6-year: β^ = -0.36, P = .001; 9-year: β^ = -0.47, P = .001). The rate of TNFα-R1 change was significantly associated with rate of eGFR change (β^ = -0.18, P = .001). Baseline sTNFα-R1 predicted incident CKD (per 1-standard deviation increment: 3-year: relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.1-1.5; 6-year: RR = 1.5, 95% CI = 1.1-2.2; 9-year RR = 1.6, 95% CI = 1.1-2.2). Similar results were found for sTNFα-R2. CONCLUSION: Baseline TNFα-R levels and their rates of change were significantly associated with RF decline and incident CKD in older adults independent of DM or blood pressure.
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