Targeting immune cell metabolism in kidney diseases

• Published in: Nature reviews. Nephrology 2021-07, Vol.17 (7), p.465-480
• Main Authors: Basso, Paulo José, Andrade-Oliveira, Vinicius, Câmara, Niels Olsen Saraiva
• Format: Article
• Language: English
• Subjects: 631/250/256; 631/443/319/333; 692/4022/1585/104; 692/4022/1585/4; Adaptive Immunity - physiology; Care and treatment; Cell metabolism; Development and progression; Energy Metabolism - immunology; Health aspects; Homeostasis; Humans; Immune response; Immune System - physiology; Immunity, Innate - physiology; Kidney diseases; Kidney Diseases - immunology; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolism; Nephrology; Observations; Review Article
• ISSN: 1759-5061; 1759-507X
• DOI: 10.1038/s41581-021-00413-7

Insights into the relationship between immunometabolism and inflammation have enabled the targeting of several immunity-mediated inflammatory processes that underlie infectious diseases and cancer or drive transplant rejection, but this field remains largely unexplored in kidney diseases. The kidneys comprise heterogeneous cell populations, contain distinct microenvironments such as areas of hypoxia and hypersalinity, and are responsible for a functional triad of filtration, reabsorption and secretion. These distinctive features create myriad potential metabolic therapeutic targets in the kidney. Immune cells have crucial roles in the maintenance of kidney homeostasis and in the response to kidney injury, and their function is intricately connected to their metabolic properties. Changes in nutrient availability and biomolecules, such as cytokines, growth factors and hormones, initiate cellular signalling events that involve energy-sensing molecules and other metabolism-related proteins to coordinate immune cell differentiation, activation and function. Disruption of homeostasis promptly triggers the metabolic reorganization of kidney immune and non-immune cells, which can promote inflammation and tissue damage. The metabolic differences between kidney and immune cells offer an opportunity to specifically target immunometabolism in the kidney. Immune cells have important roles in many kidney diseases and their phenotypes are intricately connected to their metabolic profiles. Here, the authors explore the metabolic programs of different kidney immune cells and their phenotypes, and the potential of targeting immunometabolism in the kidney. Key points The unique kidney anatomy and physiology might enable the targeting of immunometabolism as a new therapeutic strategy to treat immunity-driven kidney diseases. Immune and kidney parenchymal cells respond to a variety of stimuli by reprogramming their metabolism, which coordinates their effector functions. Targeting metabolic pathways and energy-sensing molecules has potential to prevent or ameliorate acute kidney injury and chronic kidney disease. Metabolic reprogramming of immune cells towards an anti-inflammatory profile might prevent the establishment of chronic inflammation and contribute to organ preservation after kidney injury.