Oxidized LDL Is Associated with eGFR Decline in Proteinuric Diabetic Kidney Disease: A Cohort Study

Abstract

Diabetic kidney disease (DKD) is a highly heterogenous disease, including the proteinuric and the nonproteinuric pattern. Oxidized low-density lipoprotein (ox-LDL) is progressively increased in DKD and causes direct damage to kidney tubular epithelial cells through a mechanism similar to that underlying the deleterious effect of lipid peroxides in the vascular endothelium. We aimed to examine the association between plasma ox-LDL cholesterol and clinical endpoints in DKD patients. Ninety-one patients with established proteinuric DKD and diabetic retinopathy were enrolled and prospectively followed for 10 years or the occurrence of death, or at least 30% decline in eGFR, or progression to end-stage kidney disease (ESKD) requiring renal replacement therapy (primary outcome). At the end of the study, both eGFR and proteinuria were reassessed. Secondary outcomes of the study were the percentage change in eGFR and proteinuria over time for each patient. At baseline, patients were divided into 2 groups according to the median ox-LDL value (i.e., below or equal and above 66.22 U/L). Both Kaplan-Meier curves ( $p=0.001$ , log-rank test) and univariate Cox regression analysis showed that high ox-LDL was associated with the primary outcome ( $\text{HR}=3.42$ , $95\%\text{CI}=1.55-7.56$ , $p=0.002$ ). After adjustment for various well-known cofounders, multivariate Cox analysis showed that the association between increased circulating ox-LDL levels and the composite kidney endpoint remained significant ( $\text{HR}=2.87$ , $95\%\text{CI}=1.14–7.20$ , $p=0.025$ ). Regarding the secondary outcome of eGFR decline, the assessment of areas under the curves (AUC) showed that ox-LDL outperformed several cofounding factors (AUC 71%, $95\%\text{CI}=0.59-0.83$ , $p=0.001$ ) and had better accuracy to predict deterioration of eGFR over time than baseline proteinuria (AUC 67%, $95\%\text{CI}=0.54-0.79$ , $p=0.014$ ). Increased ox-LDL might be associated with disease progression in proteinuric DKD.