Renal vein cytokine release as an index of renal parenchymal inflammation in chronic experimental renal artery stenosis

Alfonso Eirin, Xin Zhang, Xiang Yang Zhu, Hui Tang, Kyra L. Jordan, Joseph P. Grande, Allan B. Dietz, Amir Lerman, Stephen C. Textor, Lilach O. Lerman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background. Renal parenchymal inflammation is a critical determinant of kidney injury in renal artery stenosis (RAS) but is difficult to assess in the single kidney without tissue samples. Whether renal vein (RV) levels of inflammatory markers reflect active parenchymal inflammation remains unknown. We evaluated the relationship between net RV cytokine release and tissue inflammation in the post-stenotic kidney. Methods. Pigs were studied after 10 weeks of RAS treated 4 weeks earlier with intra-renal vehicle or anti-inflammatory mesenchymal stem cells (MSCs) or normal control. Single-kidney renal blood flow was measured by fast computerized tomography. RV and inferior vena cava levels of tumor necrosis factor (TNF)-α, interferon (IF)-γ, monocyte chemoattractant protein (MCP-1) and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay, and their net release calculated. Renal expression of the same cytokines was correlated with their net release. Results. Net release of TNF-α, IF-γ and MCP-1 was higher in RAS compared with normal and to the contralateral kidney (all P < 0.05), decreased in MSC-treated pigs as was their tissue expression. Contrarily, the release of the anti-inflammatory IL-10 was lower in RAS and normalized in RAS + MSC. The net release of TNF-α, MCP-1 and IL-10 directly correlated with their tissue expression. The ratio of inflammatory-to-reparative macrophages directly correlated with the release of MCP-1, but inversely with the release of IL-10. In vitro cultured MSCs also induced a shift in the macrophage phenotype from inflammatory (M1) to reparative (M2). Conclusions. Our findings demonstrate that the release of inflammatory markers from the affected kidney provides an index of renal tissue inflammation in experimental RAS.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalNephrology Dialysis Transplantation
Volume29
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • cytokines
  • hemodynamics
  • inflammation
  • renal hypertension
  • renovascular hypertension

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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