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Abstract: FR-PO721

Nampt Deficiency in Podocyte Causes Severe Glomerular and Tubular Damage Which Is Reversed by NAD+ Supplementation

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology


  • Wang, Xiaoxin, Georgetown University, Washington, District of Columbia, United States
  • Myakala, Komuraiah, Georgetown University, Washington, District of Columbia, United States
  • Levi, Moshe, Georgetown University, Washington, District of Columbia, United States

Nicotinamide adenine dinucleotide (NAD+) plays critical roles in the conversion of fuel substrate to energy and as a substrate for important enzymes that regulate cellular homeostasis. The salvage pathway is responsible for most NAD+ production in mammalian cells. As its rate-limiting enzyme, nicotinamide phosphoribosyltransferase (Nampt) deficiency in proximal tubules resulted in renal peritubular fibrotic changes, indicating the importance of NAD+ metabolism in kidney disease. However, the exact role of Nampt in podocyte has not been explored yet.


Nampt podocyte conditional knockout mice, established by crossing the podocyte specific Nphs2-cre and Nampt-flox mice, were followed from birth until 8 months of age. To examine if NAD+ is responsible for the phenotype in the podocyte Nampt deficient mice, nicotinamide was given to 8-month-old mice at 500mg/kg body weight in drinking water for 2 weeks.


The podocyte Nampt deficiency caused progressive proteinuria and renal damage. The mild proteinuria noticeable at 3-month-old mice was escalated to more than 100-fold increase in proteinuria compared to wild type mice at 8-month-old in both males and females, with massive glomerulosclerosis, tubular atrophy and fibrosis, and inflammation observed in the podocyte Nampt knockout kidneys (Figure 1). 2-week nicotinamide treatment was able to normalize the proteinuria and significantly decrease the urinary kidney injury molecule (Kim-1) level in 8-month-old podocyte Nampt knockout mice.


Our study shows that Nampt plays a critical role to maintain podocyte homeostasis, with its deletion in the podocyte causing severe proteinuria and renal damage. This effect is dependent on NAD+ as its supplementation rapidly corrects the increase in proteinuria, supporting a reversible mechanism through NAD+ metabolism instead of impairment during development.

Figure 1. Histology staining shows the severe damage in the kidneys of 8-month-old podocyte-specific Nampt knockout mice.


  • NIDDK Support