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.

Comparison of Nonalbuminuric and Albuminuric Diabetic Kidney Disease Among Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis

“…First, the phenomenon may be modified by the development of renoprotective treatments, such as renin-angiotensin system inhibitors (RASi), lipid-lowering drugs, and sodium glucose cotransporter 2 inhibitors (SGLT2i), which reduce urinary albuminuria. However, RASi was not an independent risk factor for NADKD in multivariate analysis (26), and when excluding users of RASi or lipid-lowering drugs, the prevalence and general characteristics of NADKD resembled those of all patients (12,23,39,48). Second, NADKD may be an early stage of classic DKD.…”

“…Decreased eGFR was defined as eGFR < 60 ml/min/m2. There were 5 studies with inconsistent definitions (2011 Rajiv defined albuminuria as ACR < 220 mg/g; 2019 Masayuki and 2021 Tsutomu defined albuminuria as ACR < 300 mg/g; 2013 Mauro only included patients with GFR < 30 ml/min/m2, and 2016 Ivo defined decreased eGFR as <75 ml/min/m2 (as shown in Table 2) (8,9,30,32,39). After these 5 studies were excluded, 18 studies reported the characteristics of NADKD, and they were included in the meta-analysis (5, 7, 10, 12, 15-18, 22-24, 26, 31, 34-38) (as shown in Additional Table 2).…”

Accuracy of Small Dense Low-density Lipoprotein-cholesterol Concentration Estimated via Sampson’s Equation in Healthy Subjects and Patients with Diabetes

“…Interestingly, the lower the eGFR, the greater the dissociation between direct sdLDL-C and Sampson sdLDL-C in patients with diabetes (Table 2). Renal dysfunction associated with diabetes leads to abnormal lipoprotein metabolism, resulting in the development of severe and complex dyslipidemia 14) . This may be an additional explanation for the lower ability to estimate sdLDL-C in patients with diabetes than in healthy controls.…”

“…Patients with diabetes (n=1542), including 51 type 1 diabetes, participated in the "ViNA" cohort study aimed to investigate the prognosis of patients with diabetes at Ebina General Hospital 14) . The ViNA cohort study began on October 1, 2019, and the baseline blood samples were collected from October 2019 to December 2021.…”

Role of Serum Triglycerides in Development and Progression of Diabetic Nephropathy

“…Diabetic nephropathy definition under the broad term of Chronic renal(kidney) disease (abbreviated as CKD) is coined as occurrence of renal functions deterioration and the estimated rate (eGFR) of glomerular filtration < 60 ml per min per 1.73 meter square of body surface area, present for a period of 3 months or - ---------------------------------------------------------------------------------------Received on 09-03-2022 Accepted on 17-07-2022 more 14 . In the past few years, elevation of serum triglyceride has been related to onset and progression of nephropathy in diabetics 15 .…”