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Recovery of Water Homeostasis in Adenine-Induced Kidney Disease Is Mediated by Increased AQP2 Membrane Targeting

Jasmine C L Atay1, Søren H Elsborg1, Johan Palmfeldt2

  • 1Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.

International Journal of Molecular Sciences
|March 28, 2024
PubMed

Insights

This study shows adenine-induced chronic kidney disease (CKD) in mice impairs kidney function and water balance. A two-week recovery partially restores function but not all kidney damage, highlighting the need for comprehensive monitoring.

Area of Science:

  • Nephrology
  • Pathology
  • Animal Models

Background:

  • Chronic kidney disease (CKD) is a growing global health issue.
  • Existing therapies primarily slow CKD progression, necessitating novel treatments.
  • Effective animal models are crucial for studying CKD reversibility and regeneration.

Purpose of the Study:

  • To investigate the effects of adenine-induced CKD on kidney function, injury, and homeostasis in mice.
  • To evaluate the recovery process after adenine diet cessation.
  • To characterize the reversibility of functional and structural kidney damage.

Main Methods:

  • CKD was induced in mice using a 0.2% adenine-enriched diet for 4 weeks.
  • Mice underwent a recovery period of 1 or 2 weeks post-adenine diet.
  • Kidney function, urine osmolality, aquaporin-2 (AQP2) expression, and histological markers were assessed.

Main Results:

  • Adenine diet induced impaired renal function, tubular injury, inflammation, and fibrosis.
  • Urine osmolality and AQP2 expression/targeting decreased significantly after adenine treatment.
  • Recovery led to improved urine osmolality and AQP2 levels, but only partial reversal of structural damage.

Conclusions:

  • Adenine-induced CKD in mice presents with functional and structural kidney damage.
  • A two-week recovery period partially restores kidney function and water homeostasis.
  • Complete reversal of inflammation, tubular damage, and fibrosis was not observed, indicating the need for comprehensive monitoring.
Keywords:
aquaporinchronic kidney diseasekidney fibrosisregeneration

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