Lipid Accumulation and Chronic Kidney Disease

Abstract

Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.

Keywords: blood lipids; chronic kidney disease; lipid accumulation; metabolic disease; potential therapeutic strategy.

Figure 1

Representative images of BODIPY staining (A,B) in kidney sections from chow diet (A) and high fat diet (HFD) (B) mice. Scale bar = 50 μm. Analysis of BODIPY staining in different kidney sections (C). Total cholesterol content in the kidney from different groups (D). n = 6 mice/group, * p < 0.05. Representative images of immunostaining for FATP4 (E and F) and 4-HNE (G and H) in kidney sections from chow and HFD mice. Scale bar = 50 μm.

Figure 2

Schematic representation of fatty acids cellular uptake in the kidneys. FA transport across the plasma membrane occurs mainly by protein-mediated mechanisms either with CD36 or with FATPs. In the cells, FAs bind to different FABPs with respect to the subcellular localization and have multiple functions in energy generation and storage, membrane synthesis and activation of nuclear transcription factors like PPAR/RXR. NEFA, non-esterified fatty acid; FATP, fatty acid transport protein; FABP, fatty acid-binding protein; PPAR, peroxisome proliferator activated receptor; RXR, retinoid X receptor; TG, triglyceride.