Proteoglycan binding as proatherogenic function metric of apoB-containing lipoproteins and chronic kidney graft failure

Hannah L.M Steffen,Josephine L.C Anderson,Margot L Poot,Yu Lei,Margery A Connelly,Stephan J.L Bakker,Katariina Öörni,Uwe J.F Tietge

doi:10.1016/j.jlr.2021.100083

Abstract

Lipoprotein-proteoglycan binding is an early key event in atherosclerotic lesion formation and thus conceivably could play a major role in vasculopathy-driven chronic graft failure and cardiovascular mortality in renal transplant recipients. The present study investigated whether lipoprotein-proteoglycan binding susceptibility (LPBS) of apoB-containing lipoproteins and levels of the classical atherosclerosis biomarker LDL-C were associated with cardiovascular mortality (n = 130) and graft failure (n = 73) in 589 renal transplant recipients who were followed up from at least 1 year after transplantation for 9.5 years. At baseline, LPBS was significantly higher in patients who subsequently developed graft failure than in those with a surviving graft (1.68 ± 0.93 vs. 1.46 ± 0.49 nmol/mmol, P = 0.001). Cox regression analysis showed an association between LPBS and chronic graft failure in an age- and sex-adjusted model (hazard ratio: 1.45; 95% CI, 1.14–1.85; P = 0.002), but no association was observed with cardiovascular mortality. LDL-C levels were not associated with graft failure or cardiovascular mortality. This study shows that measurement of cholesterol retention outperformed the traditionally used quantitative parameter of LDL-C levels in predicting graft failure, suggesting a higher relevance of proatherogenic function than the quantity of apoB-containing lipoproteins in chronic kidney graft failure.

Highlights

Supplementary key words kidney transplantation chronic graft failure transplant vasculopathy proteoglycans cholesterol atherosclerosis LDL prospective lipoproteinproteoglycan binding susceptibility cardiovascular mortality yahoo.com
Atherosclerosis negatively impacts the prognosis of renal transplant recipients (RTRs) in two ways, (i) in the form of pre-existing, mostly complex atherosclerotic lesions, which are the underlying pathology for CVD and (ii) as de novo atherosclerotic lesion formation in the graft, known as transplant vasculopathy (TV), the single major cause for chronic graft failure (GF) [1,2,3]
The results of this study demonstrate that beyond the static measurement of circulating LDL-C levels, functional metrics determining lipoprotein retention to proteoglycans such as lipoprotein-proteoglycan binding susceptibility (LPBS) can provide useful clinical information

Summary

Introduction

A decrease in renal function over time further contributes to the increased risk The substrate for this chronic graft functional decline is TV, an atherosclerotic process in the vasculature of the transplanted organ, affecting 50% of allografts after 5 years and 90% after 10 years [2, 3]. In RTRs, classical CVD risk factors, such as levels of LDL-C or HDL-C, fail to serve as predictive biomarkers either for CVD events or for de novo atherosclerosis leading to TV-mediated chronic GF [1, 3, 5]. In the present work, we investigated, whether in comparison to LDL-C levels, the lipoprotein-proteoglycan binding susceptibility (LPBS) of apoB-containing lipoproteins is prospectively associated with the two clinically relevant atherosclerosisrelated outcomes in RTRs, CVD mortality on the one hand and chronic GF on the other

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