Dyslipidemia in diabetic kidney disease classified by proteinuria and renal dysfunction: A cross-sectional study from a regional diabetes cohort

Abstract

Aims/introduction: Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied.

Materials and methods: Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate <60 mL/min/1.73 m² in the absence or presence of urinary albumin-to-creatinine ratio >300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay.

Results: The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria.

Conclusions: Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Keywords: Diabetic kidney disease; Low-density lipoprotein triglycerides; Small dense low-density lipoprotein cholesterol.

Figure 1

Plasma lipid levels in the groups classified by chronic kidney disease and proteinuria. Significances between groups were evaluated by Tukey–Kramer's honestly significant difference test. Proteinuria was defined as macroalbuminuria (urinary albumin‐to‐creatinine ratio [UACR] >300 mg/g), and chronic kidney disease was defined as reduced estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m²). Non‐diabetic kidney disease (DKD): UACR <300 mg/g and eGFR >60 mL/min/1.73 m², proteinuria alone: UACR >300 mg/g and eGFR >60 mL/min/1.73 m², non‐proteinuric DKD: UACR <300 mg/g and eGFR <60 mL/min/1.73 m², proteinuric DKD: UACR >300 mg/g and eGFR <60 mL/min/1.73 m². ^a P < 0.05 versus non‐DKD group, ^b P < 0.05 versus proteinuria alone group, ^c P < 0.05 versus non‐proteinuric DKD group and ^d P < 0.05 versus proteinuric DKD group. ApoCIII, apolipoprotein CIII; Lp(a), lipoprotein(a); sdLDL‐C, small dense low‐density lipoprotein cholesterol; TG, triglycerides; TRL‐C, triglyceride‐rich lipoprotein cholesterol.