Does Zn deficiency promote kidney damage?

Abstract

Background: Chronic kidney disease (CKD) impairs the kidneys’ ability to filter blood. End stage renal disease (ERSD), which is characterized by irreversible kidney fibrosis, progresses from CKD. Significant events in kidney fibrosis include the transformation of activated renal cells into myofibroblasts which can be detected by the abundance of ⍺-SMA, and the subsequent deposition of Extracellular Matrix Proteins (ECM). Previous studies have shown CKD patients are zinc deficient which is a critical micronutrient that is responsible for supporting several physiological processes in the body. Based on these findings, we hypothesize that zinc deficiency promotes kidney fibrosis. Experimental Design: To investigate the role of zinc in renal damage, wild type, adult mice (C57BL/6J) were on either a Zn-adequate (ZnA) or a Zn-deficient (ZnD) diet for 10 weeks. To examine the effects of Zn repletion (ZnR), at week 8, a subset of ZnD mice was returned to the ZnA diet. At the end of the study, kidneys were harvested and processed for immunohistochemistry to assess kidney fibrosis. Results: While ZnD mice had greater expression of ⍺-SMA, enhanced ECM deposition was not observed. However, increased ECM deposition was present in ZnR mice. Conclusion: Even though ZnD promotes activation of ECM producing cells, renal fibrosis was absent. Significance: These findings indicate a complicated interplay between Zn homeostasis and kidney fibrosis that warrants further investigation. 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.