AUTHOR=Jeon Junseok , Lee Kyungho , Yang Kyeong Eun , Lee Jung Eun , Kwon Ghee Young , Huh Wooseong , Kim Dae Joong , Kim Yoon-Goo , Jang Hye Ryoun 

TITLE=Dietary Modification Alters the Intrarenal Immunologic Micromilieu and Susceptibility to Ischemic Acute Kidney Injury

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.621176

DOI=10.3389/fimmu.2021.621176

ISSN=1664-3224

ABSTRACT=The versatility of intrarenal immunologic micromilieu through dietary modification and the subsequent effects on the susceptibility to ischemic acute kidney injury (AKI) are unclear. We investigated the effects of high-salt or high-fat diets on intrarenal immunologic micromilieu and the development of ischemic AKI using murine ischemic AKI and HK-2 cell hypoxia models. Four different diet regimens (control, high-fat, high-salt, and high-fat with high-salt) were provided to each group of 9-week male C57BL/6 mice for 1 or 6 weeks. After a bilateral ischemia-reperfusion injury (BIRI) operation, mice were sacrificed on day 2 and renal injury was assessed with intrarenal leukocyte infiltration. HK-2 cells were treated with NaCl or lipids.  The high-fat diet increased body weight and total cholesterol, whereas the high-fat diet with high-salt did not. Although the high-salt or high-fat diet did not change the total leukocytes infiltration at 6 weeks, the high-fat diet and high-fat diet with high-salt increased intrarenal CD8 T cells. Plasma cells increased in the high-fat and high-salt diet groups. The expression of proinflammatory cytokines including TNF-α, IFN-γ, MCP-1, and RANTES was increased by the high-salt or high-fat diet, and intrarenal VEGF decreased in the high-salt and high-fat with high-salt diet groups at 6 weeks. Deterioration of renal function following BIRI tended to be aggravated by the high-fat or high-salt diet. High NaCl concentration suppressed proliferation and enhanced the expression of TLR-2 in hypoxic HK-2 cells. The high-salt or high-fat diets may enhance susceptibility to ischemic AKI by inducing proinflammatory changes to the intrarenal immunologic micromilieu.