Changes in soluble tumor necrosis factor receptor type1 levels and early renal function decline in patients with diabetes.

Richard J Macisaac,Ray Boston,Matthew Farag,Glenn M Ward,Varuni Obeyesekere,Elif I Ekinci,Michele Clarke,George Jerums

doi:10.1111/jdi.13061

Richard J Macisaac, Ray Boston + Show 6 more

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https://doi.org/10.1111/jdi.13061

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Abstract

The relationship between serial changes in soluble tumor necrosis factor receptor type 1 (TNFR1) levels and an early decline in estimated glomerular filtration rate (eGFR) decline remains to be defined. We found that in patients with an early decline in renal function (n = 30), soluble TNFR1 values increased (2,595 ± 683 vs 3,596 ± 1,203 pg/mL, P < 0.001) as eGFR decreased (89 ± 1 vs 51 ± 2 mL/min/1.73m2, P < 0.001) over an 8‐year period. In contrast, there were no significant changes in soluble TNFR1 levels in patients with stable renal function (n = 17). In a multilevel mixed effects regression model, changes in soluble TNFR1 levels were found to be independently associated with eGFR decline (Z = −4.31, P < 0.001). An early decline in eGFR is associated with an increase in soluble TNFR levels; however, the factors driving this increase and the possible pathological role that soluble TNFR1 plays in progressive diabetic kidney disease remain to be determined.

Highlights

Low-grade chronic inflammation is increasingly recognized as a major driver for the development and progression of diabetic kidney disease (DKD)[1,2,3,4]
EGFR values progressively decreased during the follow-up period (F = 90, P < 0.001) in the early declining group, with this decrease being accompanied by a significant increase in sTNFR1 values (F = 90.0, P < 0.001)
In the early estimated glomerular filtration rate (eGFR) declining group, a significant increase in sTNFR1 levels was already apparent after 2–4 years of follow up

Summary

Introduction

Low-grade chronic inflammation is increasingly recognized as a major driver for the development and progression of diabetic kidney disease (DKD)[1,2,3,4]. Baseline serum levels of soluble TNFRs (sTNFRs) are linked to the progression of DKD, and might have a stronger prognostic ability for the development of end-stage renal disease than albuminuria[6]. A recent study has shown that baseline sTNFR levels are independently associated with a higher risk of estimated glomerular filtration rate (eGFR) decline in the setting of early or advanced DKD7. The aim of the present pilot study was to compare changes in sTNFR1 levels in patients with stable or an early decline in renal function

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