Significance: Chronic kidney disease (CKD) can be regarded as a burden of lifestyle disease that shares common underpinning features and risk factors with the aging process; it is a complex constituted by several adverse components, including chronic inflammation, oxidative stress, early vascular aging, and cellular senescence. Recent Advances: A systemic approach to tackle CKD, based on mitigating the associated inflammatory, cell stress, and damage processes, has the potential to attenuate the effects of CKD, but it also preempts the development and progression of associated morbidities. In effect, this will enhance health span and compress the period of morbidity. Pharmacological, nutritional, and potentially lifestyle-based interventions are promising therapeutic avenues to achieve such a goal. Critical Issues: In the present review, currents concepts of inflammation and oxidative damage as key patho-mechanisms in CKD are addressed. In particular, potential beneficial but also adverse effects of different systemic interventions in patients with CKD are discussed. Future Directions: Senotherapeutics, the nuclear factor erythroid 2-related factor 2-kelch-like ECH-associated protein 1 (NRF2-KEAP1) signaling pathway, the endocrine klotho axis, inhibitors of the sodium-glucose cotransporter 2 (SGLT2), and live bio-therapeutics have the potential to reduce the burden of CKD and improve quality of life, as well as morbidity and mortality, in this fragile high-risk patient group. Antioxid. Redox Signal. 35, 1426-1448.
Keywords: aging; allostatic load; chronic kidney disease; end-stage kidney disease; inflammation; oxidative stress; premature aging; senescence; uremic toxins.