Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study

Lay Summary The concept of lipid-induced kidney injury was proposed in 1982, but the detailed relationship of lipid parameters with kidney function decline (KFD) has not been fully elucidated. We found that serum triglycerides (TG) and TG/high-density lipoprotein cholesterol (HDL-C) ratio contributed linearly to KFD and this was partially mediated by systemic arterial stiffening assessed by cardio-ankle vascular index, but low-density lipoprotein cholesterol showed no significant contribution. A U-shaped relationship was observed between HDL-C and the risk of kidney function decline. The cut-off values independently associated with KFD were TG 82 mg/dL, HDL-C 65 mg/dL and TG/HDL-C ratio 1.28. Predicting KFD requires attention to lipid parameters in the context of vascular function. Background Dyslipidemia is associated with kidney function decline (KFD), although the non-linear relationship of lipid parameters to KFD has not been fully elucidated. We aimed to determine the detailed relationship of baseline lipid parameters with KFD, considering the mediation of arterial stiffness. Methods A total of 27 864 urban residents with estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2) at baseline, who participated in a median of three (range two to eight) consecutive annual health examinations were studied. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI). KFD was defined as development of eGFR Results During the study period, 1837 participants (6.6%) developed KFD. Receiver operating characteristic analysis determined that the cutoff values independently associated with KFD are 123 mg/dL for low-density lipoprotein cholesterol (LDL-C) [area under the curve (95% confidence interval) 0.570 (0.557-0.583)], 65 mg/dL for high-density lipoprotein cholesterol (HDL-C) [0.552 (0.539-0.566)], 82 mg/dL for triglycerides (TG) [0.606 (0.593-0.618)] and 1.28 for TG/HDL-C ratio [0.600 (0.587-0.612)]. These cut-offs were independently associated with KFD in Cox analysis. Regarding the contribution of each lipid parameter to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A adjusted mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed (mediating rate: 2.9% in TG, 2.5% in TG/HDL-C ratio). Regarding the association to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed after adjustment for confounders. Conclusions TG and TG/HDL-C ratio related linearly to KFD and this was partially mediated by CAVI. A U-shaped relationship was observed between HDL-C and KFD risk. LDL-C showed no significant association. Further study should investigate whether intensive TG-lowering treatment prevents KFD via decreasing CAVI.