419-P: Association of Remnant Cholesterol (rem-C) with Kidney Disease Progression in People with Type 2 Diabetes (T2D)

Objective: A study using diabetic mice demonstrated that cholesterol deposition in the kidneys provokes apoptosis of podocytes and albuminuria; however, most studies in people with diabetes have failed to demonstrate significant association of higher LDL cholesterol (LDL-C) levels with progression of diabetic nephropathy (DN). Accumulating evidences reveal a strong atherogenicity of cholesterol in triglyceride-rich lipoproteins, called rem-C. Currently, data on the association between rem-C and DN are limited. Here, we examined whether rem-C can predict kidney disease progression in people with diabetes.

Methods: This was a retrospective cohort study of 5161 Japanese adults with T2D (mean age: 61 years, women: 36.4%). The exposure was serum rem-C levels at baseline, treated as a categorical variable and classified into four categories based on the quartile of rem-C. Rem-C was calculated as total cholesterol minus LDL-C minus HDL cholesterol, referencing previous studies. The outcome was a composite of a ≥30% decline in eGFR or the initiation of kidney replacement therapy. The hazard ratios (HRs) for the outcome were estimated using the multivariable Cox proportional hazards model. In the analysis treating rem-C as a continuous variable, the multivariable-adjusted restricted cubic spline model was used.

Results: The median (interquartile range: IQR) baseline rem-C (mg/dL) was 25 (18-35). During a median (IQR) follow-up of 7.6 (3.0-11.6) years, 1172 people reached the outcome. In setting the first quartile group (n= 1257) as the reference, the HRs (95% CIs) of the second (n= 1302), third (n= 1304), and fourth quartile groups (n= 1298) were 1.13 (0.92-1.39), 1.38 (1.10-1.74), and 1.36 (1.01-1.81), respectively. A similar trend was also shown by the spline model.

Conclusion: Rem-C levels were identified as a risk factor for kidney disease progression in people with T2D. Future interventional studies are needed to clarify the potential of rem-C as a therapeutic target for DN.