Chronic low-grade
inflammation underlies the pathogenesis of
non-communicable diseases, including
chronic kidney diseases (CKD).
Inflammation is a biologically active process accompanied with biochemical changes involving energy,
amino acid,
lipid and
nucleotides. Recently, glycolysis has been observed to be increased in several inflammatory disorders, including several types of
kidney disease. However, the factors initiating glycolysis remains unclear. Added
sugars containing
fructose are present in nearly 70 percent of processed foods and have been implicated in the etiology of many
non-communicable diseases. In the kidney,
fructose is transported into the proximal tubules via several transporters to mediate pathophysiological processes.
Fructose can be generated in the kidney during
glucose reabsorption (such as in diabetes) as well as from intra-renal
hypoxia that occurs in CKD.
Fructose metabolism also provides biosynthetic precursors for
inflammation by switching the intracellular metabolic profile from mitochondrial oxidative phosphorylation to glycolysis despite the availability of
oxygen, which is similar to the Warburg effect in
cancer. Importantly,
uric acid, a byproduct of
fructose metabolism, likely plays a key role in favoring glycolysis by stimulating
inflammation and suppressing
aconitase in the tricarboxylic acid cycle. A consequent accumulation of glycolytic intermediates connects to the production of biosynthetic precursors,
proteins,
lipids, and
nucleic acids, to meet the increased energy demand for the local
inflammation. Here, we discuss the possibility of
fructose and
uric acid may mediate a metabolic switch toward glycolysis in CKD. We also suggest that
sodium-glucose cotransporter 2 (
SGLT2) inhibitors may slow the progression of CKD by reducing intrarenal
glucose, and subsequently
fructose levels.