Nicotinamide ameliorates podocyte injury and albuminuria in adriamycin-induced nephropathy

Podocytes are key components of the glomerular filtration barrier, and their injury leads to proteinuria, chronic kidney disease (CKD), and nephrotic syndrome. Effective treatments for these conditions are not well established, and prevention of podocyte injury is a crucial challenge. Nicotinamide (NAM), a form of vitamin B3, has been reported to exert beneficial effects in various renal disease models due to its antioxidant and anti-inflammatory properties and its ability to replenish nicotinamide adenine dinucleotide (NAD⁺). However, its impact on adriamycin (ADR)-induced nephropathy, a model of nephrotic syndrome caused by podocyte injury, remains unclear. We investigated the effects of NAM administration in a mouse model of ADR nephropathy. BALB/c mice were intravenously administered ADR to induce nephropathy. In the NAM-treated group, mice received 0.6% NAM in drinking water ad libitum starting 7 days before ADR administration. After 14 days, NAM treatment decreased albuminuria, glomerular sclerosis, and podocyte injury, and reduced inflammation and oxidative stress markers in the kidneys. NAM and NAD⁺ levels were decreased in ADR-treated kidneys, and the expression of the NAD⁺-consuming enzymes SIRT1 and poly(ADP-ribose) polymerase 1 (PARP-1) was decreased and increased, respectively. Nicotinamide <i>N</i>-methyltransferase expression was increased. NAM canceled these abnormalities. In cultured rat podocytes, NAD⁺ alleviated ADR-induced cytotoxicity, apoptosis, and inflammation. These findings suggest that NAM prevents ADR nephropathy and podocyte injury, likely through NAD⁺ replenishment.<b>NEW & NOTEWORTHY</b> Nephrotic syndrome can lead to end-stage kidney disease and cause severe complications. Currently, effective treatments for nephrotic syndrome have not been established, and new therapeutic approaches targeting podocyte injury are needed. Nicotinamide prevents podocyte injury in adriamycin-induced nephropathy in mice and ameliorates albuminuria, pathological changes, oxidative stress, and inflammation. Here, we provide evidence that pretreatment with nicotinamide can attenuate podocyte injury and subsequent nephropathy in mice.