Endocrine Abstracts

JOINT1236

Background and Aims: Diabetic kidney disease (DKD) is associated with alterations in lipid and lipoprotein metabolism, worsening kidney function and increasing cardiovascular disease (CVD) risk. Changes in HDL composition, proteomics, and functionality have been reported in DKD. This study analyzed HDL lipidome in non-dialysis DKD patients, categorized by estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER), to identify potential biomarkers for DKD progression and CVD risk.

Methods: DKD patients were classified into three groups: EA1A2 (early-stage DKD, AER A1–A2, eGFR ≥ 45; n = 21), AA1A2 (advanced DKD, AER A1–A2, eGFR < 45; n = 9), and AA3 (advanced DKD, AER A3, eGFR < 45; n = 24). Age-matched controls (C; eGFR > 60, AER < 30; n = 7) were included. The study was approved by the local ethics committee, and all participants provided written informed consent. HDL was isolated by ultracentrifugation (D = 1. 063–1. 21 g/mL) and analyzed via high-performance liquid chromatography-mass spectrometry (HPLC-MS). Lipidomic data were processed using MetaboAnalyst 6. 0, with statistical analyses conducted via Student’s t-test, ANOVA, and Kruskal-Wallis test.

Results: The study population comprised 61% men and 39% women. Baseline characteristics, including age, body mass index, total cholesterol, LDL-C, HDL-C, and triglycerides (TG), were comparable across groups. No significant differences were observed in diabetes duration or glycated hemoglobin levels among DKD groups. Among 480 lipid species identified in HDL, six showed significant reductions across four groups, including four sphingomyelins (SM), one lysophosphatidylcholine (LPC) and one phosphatidylcholine (PC). Compared to controls, EA1A2 exhibited a reduction of 21 lipid species, primarily from the lipid core (cholesteryl esters, sterols and TG). AA1A2 and AA3 exhibited reductions in 132 and 86 lipid species, respectively, compared to controls, predominantly affecting surface lipids, including SM, PC, LPC and ceramides (Cer). Only four lipid species differed significantly between AA3 and AA1A2, whereas 70 species (41. 4% SM, 30% PC, 11% Cer, 7. 1% free fatty acids, 4. 3% plasmalogens, 2. 8% LPC, and 2. 8% prenol) were consistently reduced in advanced DKD, irrespective of albuminuria severity.

Conclusion: DKD progression is associated with extensive remodeling of the HDL lipidome, characterized by early reductions in core lipids and progressive depletion of surface lipids in advanced stages. These changes, independent of albuminuria, may impair HDL functionality and exacerbate cardiovascular risk. Further research is warranted to assess their potential as biomarkers for DKD progression and CVD risk stratification.