High-Density Lipoprotein in Patients with Diabetic Kidney Disease: Friend or Foe?

High-density lipoprotein (HDL) exhibits multiple metabolic protective functions, such as facilitating cellular cholesterol efflux, antioxidant, anti-inflammatory, anti-apoptotic and anti-thrombotic properties, showing antidiabetic and renoprotective potential. Diabetic kidney disease (DKD) is considered to be associated with high-density lipoprotein cholesterol (HDL-C). The hyperglycemic environment, non-enzymatic glycosylation, carbamylation, oxidative stress and systemic inflammation can cause changes in the quantity and quality of HDL, resulting in reduced HDL levels and abnormal function. Dysfunctional HDL can also have a negative impact on pancreatic β cells and kidney cells, leading to the progression of DKD. Based on these findings, new HDL-related DKD risk predictors have gradually been proposed. Interventions aiming to improve HDL levels and function, such as infusion of recombinant HDL (rHDL) or lipid-poor apolipoprotein A-I (apoA-I), can significantly improve glycemic control and also show renal protective effects. However, recent studies have revealed a U-shaped relationship between HDL-C levels and DKD, and the loss of protective properties of high levels of HDL may be related to changes in composition and the deposition of dysfunctional particles that exacerbate damage. Further research is needed to fully elucidate the complex role of HDL in DKD. Given the important role of HDL in metabolic health, developing HDL-based therapies that augment HDL function, rather than simply increasing its level, is a critical step in managing the development and progression of DKD.