MO627ASSOCIATION OF OXIDIZED LDL CHOLESTEROL WITH MORTALITY AND PROGRESSION OF PROTEINURIC DIABETIC KIDNEY DISEASE
Authors: Roumeliotis Stefanos , Roumeliotis Athanasios , Stamou Aikaterini , Divanis Dimitrios , Theodoridis Marios , Panagoutsos Stylianos , Liakopoulos Vassilios 
Published: May 2021

Abstract

Background and Aims
Oxidative modification of low-density lipoprotein (oxLDL) contributes to the pathogenesis and progression of oxidative stress (OS) and atherosclerosis in both Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD). Compared to normo-and micro-albuminuric, T2DM patients with macroalbuminuria have significantly higher plasma oxLDL levels. In this study we aimed to assess the possible predictive role of oxLDL for mortality and deterioration of renal function in a cohort of patients with proteinuric diabetic CKD.

Method
91 patients with diabetic retinopathy, persistent proteinuria and eGFR below 90ml/min were recruited. At baseline, oxLDL, proteinuria and eGFR were assessed and patients were categorized according to median oxLDL (above or below 66.22 U/L). All patients were prospectively followed for a period of 10 years or the occurrence of a combined outcome of mortality or at least 30% decline in eGFR and/or progression to end stage renal disease (ESRD), requiring renal replacement therapy. At the end of the follow-up period, renal function was re-assessed with a new estimation of eGFR, using the CKD-EPI formula. We performed a statistical analysis with receiver operation curves (ROC) to further examine the possible effect of oxLDL on the percentage change in eGFR and proteinuria over time (calculated as ΔeGFR/baseline eGFR and Δproteinuria/baseline proteinuria respectively) and divided by the follow-up time.

Results
The mean age of the patients was 67.02±8.2 years, and the mean duration of T2DM was 14.5±8.0 years. At baseline, compared to the low, patients with high circulating oxLDL levels had significantly higher levels of triglycerides, higher diastolic blood pressure and lower eGFR (P=0.001, P=0.04 and P-0.013, respectively, Mann-Whitney test). After a 10-year follow up, 10/46 patients in the low and 20/45 patients in the high ox-LDL group presented the composite outcome. Kaplan-Meier curves (Figure 1) showed that patients with oxLDL levels above median (&gt;66.22 U/L) presented a significantly higher risk for the outcome compared to the low oxLDL group (P=0.001, log-rank test). Univariate Cox proportional hazard analysis revealed that high circulating oxLDL levels were independent predictors of the composite endpoint (HR=3.42, 95%CI: 1.55-7.56, P=0.002). After adjustment for all factors that were associated with the outcome in univariate models (baseline proteinuria, serum albumin, duration of T2DM and triglycerides), multivariate Cox analysis showed that the association between high oxLDL levels and the study endpoint remained significant (HR=3.76, 95%CI: 1.52-9.27, P=0.004). At ROC analysis the area under the curve (AUC) for oxLDL to identifying progressor patients was 0.68 (95% CI: 0.56-0.80, P=0.005). Of note, this AUC was virtually identical to that of baseline proteinuria. OxLDL failed to show any association with the change of proteinuria over time.

Conclusion
Circulating ox-LDL might play an important role in the progression of proteinuric DKD.