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

ABSTRACT: 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.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)-?, interferon (IF)-?, 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.Net release of TNF-?, IF-? 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-?, 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).Our findings demonstrate that the release of inflammatory markers from the affected kidney provides an index of renal tissue inflammation in experimental RAS.

SUBMITTER: Eirin A

PROVIDER: S-EPMC3910338 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

Eirin Alfonso A Zhang Xin X Zhu Xiang-Yang XY Tang Hui H Jordan Kyra L KL Grande Joseph P JP Dietz Allan B AB Lerman Amir A Textor Stephen C SC Lerman Lilach O LO

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20131003 2

<h4>Background</h4>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.<h4>Methods</h4>Pigs were studied after 10 weeks of RAS treated 4 weeks earlie ...[more]

PMID: 24097799

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Project description:As a non-invasive, side effect-free and cost-effective method, ultrasonography represents the method of choice for the diagnosis of renal artery stenosis. Four different criteria in total, including two direct criteria in peak systolic velocity (PSV) and renal aortic ratio (RAR) and two indirect criteria in resistance index (RI) and acceleration time (AT) for the measurement of relevant renal artery stenosis are described, each demonstrating highly variable accuracy in studies. Furthermore, there is controversy over the degree beyond which stenosis becomes therapeutically relevant and which ultrasound PSV is diagnostically relevant in terms of stenosis grading.This article gives a critical review based on a selective literature search on measurement methodology and the validity of ultrasound in renal artery stenosis. A critical evaluation of methods and a presentation of measurement principles to establish the most precise measurement method possible compared with the gold standard angiography, as well as an evaluation of the importance of computed tomography angiography (CTA) and magnetic resonance angiography (MRA).The PSV provides high sensitivity and specificity as a direct measurement method in stenosis detection and grading. Most studies found sensitivities and specificities of 85-90?% for >?50?% stenosis at a PSV >?180-200 cm/s in ROC curve analysis. Other methods, such as the ratio of the PSV in the aorta to the PSV in the renal artery (RAR) or indirect criteria, such as side to side differences in RI (dRI) or AT can be additionally used to improve accuracy. Contrast-enhanced ultrasound improves accuracy by means of echo contrast enhancement. Although in the past only high-grade stenosis was considered relevant for treatment, a drop in pressure of >?20 mmHg in >?50?% stenosis (PSV 180 cm/s) is classified as relevant for increased renin secretion. Stenosis in fibromuscular dysplasia can be reliably graded according to the continuity equation. Although the available studies on the grading of in-stent restenosis are the subject of controversy, there is a tendency to assume higher cut-off values for PSV and RAR. Whilst MRA and CTA demonstrate an accuracy of >?90?%, this is at the cost of possible side effects for patients, particularly in the case of pre-existing renal parenchymal damage.This article includes two additional video sequences on visualizing renal artery stenosis. This supplemental material can be found under: dx.doi.org/10.1007/s00772-015-0060-3.

Dataset Information

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

Publications

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

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