Review examines glucose metabolic reprogramming in SLE and lupus nephritis pathogenesis

This systematic review synthesizes existing evidence on the role of glucose metabolic reprogramming—including glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle—in driving pathogenic immune cell activation in systemic lupus erythematosus and lupus nephritis. The review examines evidence related to various immune cells (monocytes/macrophages, neutrophils, dendritic cells, T cells, B cells) and renal resident cells. It does not report primary data, effect sizes, or statistical certainty, as it is a synthesis of existing literature rather than a primary study reporting new results.

The main finding is that glucose metabolic reprogramming plays a central role in driving pathogenic immune cell activation in SLE. However, the review identifies a critical gap in understanding how these metabolic alterations operate specifically within the renal microenvironment in lupus nephritis. The therapeutic strategies discussed include repurposed drugs and preclinical small molecule inhibitors targeting these metabolic pathways, but clinical efficacy for these approaches is not established in this review.

Safety considerations noted include the sensitivity of regulatory T cells to glycolysis inhibition, which underscores the need for careful dose optimization in any therapeutic approach targeting these pathways. The review's limitations stem from its nature as a synthesis; it does not establish causality, and many of the discussed therapeutic strategies remain preclinical. The practice relevance is restrained, as the review primarily outlines theoretical foundations and future research directions rather than providing evidence for immediate clinical application.