Vitamin B12 modulates D-galactose-induced renal dysfunction

Background & objectives Age-related renal impairment presents a significant challenge in contemporary clinical practice. Cellular senescence and oxidative stress are the key contributors to chronic kidney disease (CKD) during aging. Senescence is triggered by advanced glycation end products (AGEs), hyperphosphatemia, and higher glucose levels, which lead to renal dysfunction by inducing inflammation, endoplasmic reticulum (ER) stress, fibrosis, and apoptosis. Further, vitamin B12 is known to influence biological ageing and has been suggested to improve kidney function in the elderly; however, the underlying mechanisms require further investigation. In this study, we investigated the potential of vitamin B12 in mitigating renal dysfunction using a D-galactose-induced aging rat model. Methods Twelve-month-old male Wistar rats were grouped into Control, D-galactose (300 mg/kg/day), and D-galactose + vitamin B12 supplementation groups (n=6). Renal dysfunction was evaluated by kidney function markers (creatinine, albumin, urea, and BUN), renal damage markers (kidney injury molecule-1 [KIM-1], lipocalin-2 [LCN-2], fatty-acid binding protein-1 [FABP-1], and tissue inhibitor of metalloproteinase-1 [TIMP-1]), and histopathology (glomerular changes). Signalling mechanisms of cellular senescence, phosphate metabolism, inflammation, fibrosis, and renal apoptosis were analysed by qRT-PCR and immunoblotting. Results Vitamin B12 supplementation attenuated renal dysfunction by alleviating the senescence-induced accumulation of AGEs and hyperphosphatemia. Furthermore, vitamin B12 administration conferred renal protection by subsiding inflammation, fibrosis, and apoptosis through modulation of the RAGE-NFkB, pPERK-GSK3β, and JNK signalling pathways. Vitamin B12 supplementation mitigated hyperphosphatemia by mediating the Klotho-FGF23 axis. Interpretation & conclusions The findings provide evidence for vitamin B12 supplementation in managing renal aging.