Clinical and experimental nephrology

How Kidney Energy Use Relates to Chronic Kidney Disease

Updated

Abstract

Chronic kidney disease (CKD) is associated with dysregulated lipid metabolism, particularly in proximal kidney tubules.

  • Proximal tubules primarily rely on fatty acid oxidation for energy rather than glycolysis, which is reflected by the absence of key glycolytic enzymes.
  • Maladaptive hypertrophy occurs in CKD as surviving nephrons compensate to maintain kidney function.
  • PPARα is identified as a key regulator of proximal tubule cell size and compensatory hypertrophy.
  • Decreased AMPK activity in CKD impairs cellular responses to energy stress, as shown by altered AMP/ATP ratios.
  • Uremic metabolites may worsen defective energy sensing by reducing AMPK function.
  • ULK1 regulates AMPK activity by enhancing its sensitivity to AMP through specific phosphorylation sites.

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