Circulating CD40 and sCD40L Predict Changes in Renal Function in Subjects with Chronic Kidney Disease

Jeffrey X Xie,Pamela Brewster,Steven T Haller,Jiang Tian,Deepak Malhotra,Philip A Kalra,Lance D Dworkin,Yanmei Xie,Tian Chen,Rajesh Gupta,Helen Alderson,Christopher J Cooper,Kaili Ren,Hanh Nguyen,James Ritchie

doi:10.1038/s41598-017-08426-8

Jeffrey X Xie, Pamela Brewster + Show 13 more

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Journal: Scientific Reports	Publication Date: Aug 11, 2017
Citations: 17	License type: open-access

Affiliation: University of Toledo, Salford Royal Hospital

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Soluble CD40 ligand (sCD40L) has been implicated in the development of renal injury. The CD40 receptor exists in a soluble form, sCD40R, and has been shown to function as a competitive antagonist against CD40 activation. We analyzed whether plasma levels of sCD40L and sCD40R predict changes in renal function in an all-cause chronic kidney disease (CKD) cohort. Stratification of subjects based on sCD40L and sCD40R individually, as well as in combination, demonstrated that sCD40L was directly associated with declines in estimated glomerular filtration rate (eGFR). sCD40R was negatively associated with declines in eGFR. Baseline characteristics following stratification, including systolic blood pressure, history of diabetes mellitus or peripheral vascular disease, primary renal disease classification, and angiotensin converting enzyme inhibitor or angiotensin receptor blocker usage were not significantly different. High sCD40L and low sCD40R were both found to be independent predictors of a decline in eGFR at 1-year follow-up (−7.57%, p = 0.014; −6.39%, p = 0.044). Our data suggest that circulating levels of sCD40L and sCD40R are associated with changes in renal function in patients with CKD. The CD40 decoy receptor, sCD40R, may serve as a potential therapeutic target to attenuate renal function decline.

Highlights

Chronic Kidney Disease (CKD) is defined as a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2 for more than three months[1]
CD40 signaling events have been linked to atherosclerosis and thrombosis, processes which are thought to develop in part due to persistent inflammation[14,15,16,17,18]
As atherosclerotic renal artery stenosis is a known cause of CKD21, the current study builds upon our previous findings by broadening the scope of our study from renal artery stenosis to an all-cause CKD population

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Introduction

Chronic Kidney Disease (CKD) is defined as a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2 for more than three months[1]. We have shown that subjects with atherosclerotic renal artery stenosis have significantly elevated levels of circulating sCD40L19. We have shown that higher levels of baseline circulating sCD40R were associated with a higher 1-year follow-up estimated GFR (eGFR), presumably due to the ability of sCD40R to antagonize CD40-mediated signaling[20]. The primary aim of the present study is to investigate whether circulating levels of sCD40L and sCD40R are associated with changes in renal function in subjects with CKD. We analyzed the effects of plasma levels of sCD40L and sCD40R on renal and cardiac mortality, rate of renal replacement therapy (RRT), myocardial infarction, stroke, and heart failure incidence

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