Abstract
BackgroundThe role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.FindingsCystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2α [PGF2α]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).ResultsIn linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (β-coefficient −0.13 to −0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (β-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (β- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (β-coefficient −0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.ConclusionOur data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.
Highlights
The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied
The total analytical imprecision of the cystatin C assay was 4.8% at 0.56 mg/L and 3.7% at 2.85 mg/L High-sensitivity IL-6 was analysed with an ELISA kit (IL-6 HS; R&D Systems, Minneapolis, MN, USA). estimated glomerular filtration rate (eGFR) was calculated from serum cystatin C results in mL/min/1.73 m2 by the formula y = 77.24x-1.2623, which have been shown to be closely correlated with iohexol clearance [17]
We modelled C-reactive protein (CRP), prostaglandin F2α (PGF2α), IL-6, serum amyloid protein A (SAA), F2-isoprostanes, eGFR, and albumin/creatinine ratio as continuous variables
Summary
The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Untraditional cardiovascular risk factors such as oxidative stress [6,7] and inflammation [8] are more prevalent in CKD patients than in normal individuals [9], and have been associated with adverse cardiovascular outcomes [5,10,11,12] and progression of renal injury in these patients [10]. These observations suggest that oxidative stress and inflammation may have an important role in the development of CKD. F2-isoprostanes, which are prostaglandin derivatives, are formed by free-radical-catalysed peroxidation of arachidonic acid. 8-Iso-PGF2α, a major F2-isoprostane, is currently regarded as one of the most reliable indicators of in vivo lipid peroxidation and oxidative stress [14,15,16]
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