NAD(+) Metabolism and Interventions in Premature Renal Aging and Chronic Kidney Disease

Premature aging causes morphological and functional changes in the kidney, leading to chronic kidney disease (CKD). CKD is a global public health issue with far-reaching consequences, including cardio-vascular complications, increased frailty, shortened lifespan and a heightened risk of kidney failure. Dialysis or transplantation are lifesaving therapies, but they can also be debilitating. Currently, no cure is available for CKD, despite ongoing efforts to identify clinical biomarkers of premature renal aging and molecular pathways of disease progression. Kidney proximal tubular epithelial cells (PTECs) have high energy demand, and disruption of their energy homeostasis has been linked to the progression of kidney disease. Consequently, metabolic reprogramming of PTECs is gaining interest as a therapeutic tool. Preclinical and clinical evidence is emerging that NAD(+) homeostasis, crucial for PTECs’ oxidative metabolism, is impaired in CKD, and administration of dietary NAD(+) precursors could have a prophylactic role against age-related kidney disease. This review describes the biology of NAD(+) in the kidney, including its precursors and cellular roles, and discusses the importance of NAD(+) homeostasis for renal health. Furthermore, we provide a comprehensive summary of preclinical and clinical studies aimed at increasing NAD(+) levels in premature renal aging and CKD.