Lipids in kidney diseases: from systemic imbalance to intrarenal alterations of cellular lipid metabolism in rare and common kidney diseases

Chronic kidney disease (CKD) is expected to be the fifth cause of global mortality by 2040. Modifiable and non-modifiable risk factors for CKD range from metabolic conditions, such as diabetes or obesity, to genetic defects. Regardless of the triggering factor, irreversible injury and loss of kidney cells result in the decline of kidney function. Renal damage often occurs through common signaling pathways promoting inflammation, oxidative stress, organelle dysfunction, complement activation, apoptosis, and fibrogenesis. Lipotoxicity is emerging as a key player in CKD of both metabolic and non-metabolic origin. Here, we provide an overview of the mechanisms beyond renal lipid accumulation in CKD, ranging from systemic imbalance of lipid/lipoprotein metabolism to alterations of cell lipid uptake, synthesis, and disposal. Moreover, the impact of lipid accumulation in glomerular and tubular cells is addressed. Several lipid species were shown to accumulate in renal cells, from cholesterol and fatty acids to sphingolipids; they can affect cell viability and function not only as structural components of biological membranes or energetic substrates but also as bioactive molecules able to modulate multiple signaling pathways. The possible role of established and novel approaches to correct systemic or local lipid imbalance in the management of CKD is discussed.