Does zinc deficiency promote renal inflammation?

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Background: Renal inflammation is implicated in the pathogenesis of CKD and plays a critical role in kidney damage. CKD-associated tubular damage stimulates the secretion of proinflammatory cytokines (e.g. IL-1β, IL-6, and TNF-α) which expedite CKD progression, further instigating kidney damage and inflammation. Studies have shown that zinc deficiency (ZnD) elevates oxidative stress and affects proinflammatory cytokine abundance. Based on these findings, we hypothesize that ZnD will promote renal inflammation. Experimental Design: To examine if ZnD promotes renal inflammation, wild-type adult mice (C57BL/6J) were placed on a zinc-adequate (ZnA) or zinc-deficient (ZnD) diet for 10 weeks. At week 8, a subset of the ZnD mice were placed back on a ZnA diet (ZnR) for 2 weeks. The kidneys were harvested, embedded in paraffn, and both immunohistochemistry and immunofluorescence were performed to assess morphological changes and proinflammatory cytokine abundance. Results: Compared to ZnA kidneys, morphological changes were observed in ZnD kidneys, such as loss of endothelial cells in the glomerulus and abnormalities in nuclei arrangement in tubular cells. However, these changes were mitigated with the replenishment of zinc. There were no significant changes in TNF-α expression between the ZnA and ZnD kidneys, but there was decreased expression in the ZnR kidney. Conclusions: Based on preliminary findings, we can conclude that ZnD (1) promotes abnormalities in glomerular and tubular morphology and (2) does not have a significant impact on TNF-α expression in the renal cortex. Zinc repletion was shown to mitigate the glomerular and tubular abnormalities instigated by zinc deficiency. Significance: These findings provide evidence for Zn’s influence on renal inflammation, and advocate for zinc supplementation as a plausible therapeutic strategy for CKD. Funding: R21 DK119879, R01 DK-133698. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.