Highlights

  • NMN treatment restores essential kidney cells that filter waste (podocytes) and reduces the number of kidney tissue lesions in a mouse model for kidney disease. 
  • NMN increases the activation of a pro-longevity enzyme called Sirtuin-1 that reduces kidney cell damage.

Our kidneys filter out unwanted material from our bloodstream. As we get older, kidney scarring and tissue hardening can impair the ability of our kidneys to filter our blood, allowing proteins to escape into our urine with a condition called glomerulosclerosis. Treatments for severe levels of this age-related kidney dysfunction include dialysis or kidney transplants, both physically taxing procedures, so finding new ways to slow the progression of this condition is paramount.

Published in Scientific Reports, Wakino and colleagues from Tokushima University in Japan find that injecting 500 mg/kg/day of NMN reduces kidney damage in a mouse model for a rare disease called focal segmental glomerulosclerosis, which has similar pathology to age-related glomerulosclerosis. NMN restores the abundance of cells that are essential for kidney waste filtration called podocytes. What’s more, by boosting the essential molecule for cell health, nicotinamide adenine dinucleotide (NAD+), NMN increases the activation of the pro-longevity enzyme Sirtuin-1, which then reduces enzymes associated with kidney tissue damage. These findings provide the first evidence that NMN restores waste filtration cells in kidney disease.

NMN Reverses Kidney Dysfunction 

Since higher urinary protein levels are associated with kidney damage and impaired filtration, Wakino and colleagues examined how NMN affects urine protein levels. The research team established a model for glomerulosclerosis by injecting mice with a chemotherapy drug (adriamycin) that causes kidney damage. The mice modeling kidney disease had dramatically increased levels of urine protein. However, treating these mice with NMN reduced urine protein levels, suggesting reduced kidney damage and corrected protein filtration.

Since NMN reduces urinary protein levels, the Tokushima-based research team surmised that NMN may preserve the abundance of podocytes, the kidney’s waste-filtering cells. They found reduced podocyte numbers in the kidney disease mice and, as expected, NMN increased these numbers. These findings indicate that NMN improves kidney function by restoring waste-filtering podocytes and to maintain urinary protein levels.

(Hasegawa et al., 2022 | Scientific Reports) NMN restores kidney function. The albumin-to-creatinine ratio (ACR), an indicator of urinary protein abundance, dramatically increases in adriamycin-induced glomerulosclerosis mice (ADR) compared to normal mice (Cont), but NMN (NMN500) ameliorates this effet. Also, podocyte numbers decline in ADR mice, but NMN restores their numbers.

Sirtuin-1 is an enzyme that, when activated, is associated with increased lifespan. Furthemore, low Sirtuin-1 levels are associated with age-related diseases like glomerulosclerosis. Because Sirtuin-1 utilizes NAD+ as fuel and NMN boosts NAD+ levels, Wakino and colleagues examined how NMN affects Sirtuin-1 levels in the kidney disease mice. The research team found that NMN restored the low Sirtuin-1 levels in the kidneys of the mice. 

Higher Sirtuin-1 levels from NMN were also associated with kidney tissue preservation in the face of adriamycin treatment. Although adriamycin-induced kidney disease triggers much higher numbers of tissue lesions (damage), NMN restores the kidney tissue damage. Better tissue structure integrity results in better functional capacity.

(Hasegawa et al., 2022 | Scientific Reports) NMN reduces kidney tissue damage. The various shades of pink mark kidney tissue and fat cells. The white-colored separations separating tissue are lesions. Adriamycin (ADR)-treated mice have dramatically more lesions (damage), however adding NMN treatment prevents lesion buildup.

NMN Preserves the Kidney’s Waste Filtration

The study is the first to examine how NMN affects a mouse model of glomerulosclerosis. The results show that by boosting NAD+ levels and activating Sirtuin-1, NMN reduces kidney damage and restores kidney function. 

Other mouse studies examining NMN’s beneficial effects on kidneys have examined kidney scarring (fibrosis) models. This study demonstrates that NMN can also restore kidney waste filtration cells to improve kidney function. Since kidney dialysis and transplants have been the only means to treat age-related glomerulosclerosis, using NMN or related NAD+ metabolites may present new, less invasive ways to alleviate kidney disease.