Inflammation and Trajectory of Renal Function in Community‐Dwelling Older Adults

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 m 2 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 m 2 at each follow‐up. Predictors included baseline and time‐dependent inflammatory biomarkers: soluble tumor necrosis factor alpha receptors ( sTNF α ‐R1 and ‐R2), interleukin ( IL )‐6, IL ‐18, IL ‐1 β , IL ‐1 receptor antagonist, and high‐sensitivity C‐reactive protein. Results: Higher baseline sTNF α ‐R1 was significantly associated with lower eGFR over 9 years, independent of DM or blood pressure (baseline: = −0.39, P = .001; 3‐year: = −0.26, P = .001; 6‐year: = −0.36, P = .001; 9‐year: = −0.47, P = .001). The rate of TNF α ‐R1 change was significantly associated with rate of eGFR change ( = −0.18, P = .001). Baseline sTNF α ‐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 sTNF α ‐R2. Conclusion: Baseline TNF α ‐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.