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Role of triglyceride-rich lipoproteins in diabetic nephropathy

Abstract

Diabetic nephropathy is an increasingly important cause of morbidity and mortality worldwide. A large body of evidence suggests that dyslipidemia has an important role in the progression of kidney disease in patients with diabetes. Lipids may induce renal injury by stimulating TGF-β, thereby inducing the production of reactive oxygen species and causing damage to the glomeruli and glomerular glycocalyx. Findings from basic and clinical studies strongly suggest that excess amounts of a variety of lipoproteins and lipids worsens diabetes-associated microvascular and macrovascular disease, increases glomerular injury, increases tubulointerstitial fibrosis, and accelerates the progression of diabetic nephropathy. The increasing prevalence of obesity, type 2 diabetes mellitus, and diabetic nephropathy means that interventions that can interrupt the pathophysiological cascade of events induced by lipoproteins and lipids could enable major life and cost savings. This Review discusses the structural, cellular, and microscopic findings associated with diabetic nephropathy and the influence of lipoproteins, specifically triglyceride-rich lipoproteins (TGRLs), on the development and perpetuation of diabetic nephropathy. Some of the accepted and hypothesized mechanisms of renal injury relating to TGRLs are also described.

Key Points

  • In patients with diabetes, an excess of a variety of lipoproteins and lipids worsens microvascular and macrovascular disease, increases glomerular injury, increases tubulointerstitial fibrosis, and accelerates progression of diabetic nephropathy

  • Lipid abnormalities associated with diabetic nephropathy include high plasma levels of VLDL, IDL, and LDL, and low concentrations of HDL

  • Lipids may induce renal injury by stimulating TGF-β, thereby inducing the production of reactive oxygen species and causing damage to the glomeruli and glomerular glycocalyx

  • Triglyceride-rich lipoproteins can activate monocytes, degrade glycocalyx, and increase permeability of the glomerular filtration barrier, which may contribute to the progression of diabetic nephropathy

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Figure 1: Key mediators of glomerular remodeling in diabetic nephropathy.
Figure 2: Effects of type 1 diabetes on endothelial layer structure.
Figure 3: Electron microscopy image of the endothelial glycocalyx in a coronary capillary.92
Figure 4: VLDL lipolysis products induce lipid droplets in THP-1 monocytes.98
Figure 5: The effects of TGRLs in the kidney in diabetes.

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Correspondence to John C. Rutledge.

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Rutledge, J., Ng, K., Aung, H. et al. Role of triglyceride-rich lipoproteins in diabetic nephropathy. Nat Rev Nephrol 6, 361–370 (2010). https://doi.org/10.1038/nrneph.2010.59

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