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Published February 1, 2021 | Version v1
Journal article Open

Changes in NAD and Lipid Metabolism Drive Acidosis-Induced Acute Kidney Injury

  • 1. Institute of Anatomy, University of Zurich, Zurich, Switzerland
  • 2. Institute of Anatomy, University of Zurich, Zurich, Switzerland; Center for Microscopy and Image Analysis, University of Zurich, Zurich, Switzerland
  • 3. Institute of Anatomy, University of Zurich, Zurich, Switzerland; Department of Nephrology, University Hospital Zurich, Zurich, Switzerland

Description

Clinical studies have suggested that metabolic acidosis (MA) aggravates tubular damage in patients with both AKI and CKD, but the mechanisms were unknown. Intravital live cell imaging and other complementary techniques demonstrated in the mouse kidney that MA induces acute changes in the mitochondrial NAD redox state, respiratory chain function, and lipid metabolism, which collectively lead to tubular cell damage. Intravenous injection of bicarbonate increases blood pH and improves tubular function, whereas pretreatment with an NAD precursor is highly protective. Thus, changes in cell metabolism explain the harmful effects of MA on kidney tubules, which therapeutic strategies that are viable in humans can substantially ameliorate.

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Additional details

Funding

Investigating cellular dynamics in kidney tubular injury and remodeling 310030_184688
Swiss National Science Foundation
IKPP2 – International Fellowship Program on Integrative Kidney Physiology and Pathophysiology 608847
European Commission