Immunosenescence, gut dysbiosis, and chronic kidney disease: Interplay and implications for clinical management

Tao Han Lee; Jia-Jin Chen; Chao-Yi Wu; Ting-Yun Lin; Szu-Chun Hung; Huang-Yu Yang

doi:10.1016/j.bj.2023.100638

Immunosenescence, gut dysbiosis, and chronic kidney disease: Interplay and implications for clinical management

Biomed J. 2023 Jul 29;47(2):100638. doi: 10.1016/j.bj.2023.100638. Online ahead of print.

Authors

Tao Han Lee¹, Jia-Jin Chen², Chao-Yi Wu³, Ting-Yun Lin⁴, Szu-Chun Hung⁵, Huang-Yu Yang⁶

Affiliations

¹ Nephrology Department, Chansn Hospital, Taoyuan, Taiwan.
² Kidney Research Center, Nephrology Department, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
³ Division of Allergy, Asthma, And Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴ Division of Nephrology, Taipei Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi University, Taipei, Taiwan.
⁵ Division of Nephrology, Taipei Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi University, Taipei, Taiwan. Electronic address: zuchun.hung@gmail.com.
⁶ Kidney Research Center, Nephrology Department, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: hyyang01@gmail.com.

Abstract

Immunosenescence refers to the immune system changes observed in individuals over 50 years old, characterized by diminished immune response and chronic inflammation. Recent investigations have highlighted similar immune alterations in patients with reduced kidney function. The immune system and kidney function have been found to be closely interconnected. Studies have shown that as kidney function declines, both innate and adaptive immunity are affected. Chronic kidney disease (CKD) patients exhibit decreased levels of naive and regular T cells, as well as naive and memory B cells, while memory T cell counts increase. Furthermore, research suggests that CKD and end-stage kidney disease (ESKD) patients experience early thymic dysfunction and heightened homeostatic proliferation of naive T cells. In addition to reduced thymic T cell production, CKD patients display shorter telomeres in both CD4+ and CD8+ T cells. Declining kidney function induces uremic conditions, which alter the intestinal metabolic environment and promote pathogen overgrowth while reducing diversity. This dysbiosis-driven imbalance in the gut microbiota can result in elevated production of uremic toxins, which, in turn, enter the systemic circulation due to compromised gut barrier function under uremic conditions. The accumulation of gut-derived uremic toxins exacerbates local and systemic kidney inflammation. Immune-mediated kidney damage occurs due to the activation of immune cells in the intestine as a consequence of dysbiosis, leading to the production of cytokines and soluble urokinase-type plasminogen activator receptor (suPAR), thereby contributing to kidney inflammation. In this review, we delve into the fundamental mechanisms of immunosenescence in CKD, encompassing alterations in adaptive immunity, gut dysbiosis, and an overview of the clinical findings pertaining to immunosenescence.

Keywords: CKD; gut dysbiosis; immunosenescence; inflamm-aging.

Publication types

Review