Fructose Production and Metabolism in the Kidney

J Am Soc Nephrol. 2020 May;31(5):898-906. doi: 10.1681/ASN.2019101015. Epub 2020 Apr 6.

Abstract

Understanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.

Keywords: fructolysis; fructoneogenesis; fructose; gluconeogenesis; glycolysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiomegaly / etiology
  • Cardiomegaly / metabolism
  • Diabetic Nephropathies / metabolism
  • Dietary Sugars / adverse effects
  • Dietary Sugars / pharmacokinetics
  • Energy Metabolism
  • Fatty Acids / biosynthesis
  • Fructose / adverse effects
  • Fructose / metabolism*
  • Gluconeogenesis / physiology
  • Humans
  • Kidney / metabolism*
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidative Stress
  • Postoperative Complications / etiology
  • Postoperative Complications / metabolism
  • Sorbitol / metabolism
  • Uric Acid / metabolism
  • Vertebrates / metabolism

Substances

  • Dietary Sugars
  • Fatty Acids
  • Uric Acid
  • Fructose
  • Sorbitol