The sweetest thing: blocking fructose metabolism to prevent acute kidney injury?

Abstract

Fructose consumption has been linked to hypertension in animal models and human studies, and endogenous fructose metabolism has been shown to promote acute and chronic kidney injury in mice. A recent study published in Nature Communications demonstrates a reduction in ischemic acute kidney injury with genetic knockout or inhibition of fructokinase, which catalyzes the first step in fructose metabolism. Although the role of this pathway in human kidney disease remains unclear, the recent description of several candidate fructokinase inhibitors may allow for clinical studies in the future.

Figure 1. Proposed mechanisms of action of luteolin to reduce kidney injury

The polyol pathway metabolizes excess glucose to sorbitol, and fructose and is upregulated in experimental models of acute kidney injury. Andres-Hernando et al. demonstrated that genetic deletion or inhibition of fructokinase reduces ischemic acute kidney injury in mice. The fructokinase inhibitor luteolin also has other effects that could reduce kidney injury, including the inhibition of topoisomerases, the stabilization of p53, and the inhibition of STAT3.