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

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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: = −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 TNFα-R1 change was significantly associated with rate of eGFR change (= −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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