Glucose Metabolism in Acute Kidney Injury and Kidney Repair

Abstract

The kidneys play an indispensable role in glucose homeostasis via glucose reabsorption, production, and utilization. Conversely, aberrant glucose metabolism is involved in the onset, progression, and prognosis of kidney diseases, including acute kidney injury (AKI). In this review, we describe the regulation of glucose homeostasis and related molecular factors in kidneys under normal physiological conditions. Furthermore, we summarize recent investigations about the relationship between glucose metabolism and different types of AKI. We also analyze the involvement of glucose metabolism in kidney repair after injury, including renal fibrosis. Further research on glucose metabolism in kidney injury and repair may lead to the identification of novel therapeutic targets for the prevention and treatment of kidney diseases.

Keywords: SGLTs; glucose metabolism; glycolysis (warburg effect); kidney injury and repair; renal fibrosis.

Figure 1

Glucose metabolism in normal kidney. The normal kidney is involved in systemic glucose metabolism mainly in three ways: reabsorption of glucose, production of glucose (gluconeogenesis), and utilization of glucose. When the bloodstream floods into the kidneys, all of the glucose in plasma passes through the glomerulus and most is then reabsorbed by the proximal convoluted tubules (PCTs). In addition, PCTs produce glucose through gluconeogenesis during the post-absorptive phase. Different segments of the nephron have their own preferable sources of fuels for energy based on oxygen availability. PCTs in the cortex prefer free fatty acids (FFAs) for respiration, while succinate and lactate are the main fuel for the outer medulla tubules and the inner medulla mainly utilizes glucose via anaerobic glycolysis to generate ATP. Created with BioRender.com.