The diseased kidney: aging and senescent immunology

Immunosenescence is the deterioration of the innate and adaptive immune systems associated with aging and is primarily characterized by a reduction in T cell production and accumulation of atypical subsets. Age-related immunological dysfunction leads to impaired immune protection and persistent low-grade chronic inflammation, resulting in a decreased vaccination response and increased vulnerability to infection, cancer, cardiovascular disease, and autoimmune disease in the elderly. As the elderly constitute a growing proportion of the population with renal disease, immunosenescence is a normal aging process that is prevalent among older people. In addition, immunosenescence seems to be more pronounced in patients with kidney diseases than in healthy controls, as shown by severe chronic inflammation, accumulation of immune cells with the senescent phenotype (CD28^- T cells, CD14⁺CD16⁺ monocytes), and proinflammatory cytokine production. Immunosenescence inhibits immunological clearance and renal tissue regeneration, thereby increasing the risk of permanent renal damage, infection, and cardiovascular events in patients with kidney disease, lowering the prognosis, and even influencing the efficacy of renal replacement treatment. Biological drugs (senomorphics and senolytics) target the aging immune system and exert renoprotective effects. This review aims to emphasize the features of immunosenescence and its influence on kidney diseases and immunotherapy, highlighting the future directions of kidney disease treatment using senescence-focused techniques.