Abstract
Chronic inflammation plays a crucial role in the development/progression of diabetic kidney disease. The involvement of tumor necrosis factor (TNF)-related biomarkers [TNFα, progranulin (PGRN), TNF receptors (TNFR1 and TNFR2)] and uric acid (UA) in renal function decline was investigated in patients with type 2 diabetes (T2D). Serum TNF-related biomarkers and UA levels were measured in 594 Japanese patients with T2D and an eGFR ≥30 mL/min/1.73 m2. Four TNF-related biomarkers and UA were negatively associated with estimated glomerular filtration rate (eGFR). In a logistic multivariate model, each TNF-related biomarker and UA was associated with lower eGFR (eGFR <60mL /min/1.73 m2) after adjustment for relevant covariates (basic model). Furthermore, UA and TNF-related biomarkers other than PGRN added a significant benefit for the risk factors of lower eGFR when measured together with a basic model (UA, ΔAUC, 0.049, p < 0.001; TNFα, ΔAUC, 0.022, p = 0.007; TNFR1, ΔAUC, 0.064, p < 0.001; TNFR2, ΔAUC, 0.052, p < 0.001) in receiver operating characteristic curve analysis. TNFR ligands were associated with lower eGFR, but the associations were not as strong as those with TNFRs or UA in patients with T2D and an eGFR ≥30 mL/min/1.73 m2.
Highlights
Chronic low-grade inflammation may induce chronic kidney disease (CKD) in patients with diabetes
Serum levels of TNFα, PGRN, TNFR1, and TNFR2 in the estimated glomerular filtration rate (eGFR)
The major finding in this large cross-sectional study was that circulating tumor necrosis factor (TNF)-related inflammatory biomarkers (TNFα, PGRN, TNFR1, and TNFR2) were associated with two important renal traits (ACR and eGFR) in Japanese patients with type 2 diabetes (T2D) and an eGFR ≥30 mL/min/1.73 m2
Summary
Chronic low-grade inflammation may induce chronic kidney disease (CKD) in patients with diabetes. Circulating levels of TNF receptors (TNFRs; TNFR1, TNFR2), which are the surface receptors of TNFα, in patients with diabetes have been associated with renal traits (albuminuria and eGFR) as well as cardiovascular disease (CVD) and all-cause mortality in both cross-sectional and longitudinal studies[4,5,6,7,8,9,10,11,12,13,14,15,16]. Little is known about whether PGRN is associated with classical TNF-related biomarkers (TNFα and TNFRs). The aim of this study was to determine the associations among TNF-related biomarkers, UA, and renal function in a large cohort of Japanese patients with T2D and eGFR ≥30 mL/min/1.73 m2
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