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Raised plasma Robo4 and cardiac surgery-associated acute kidney injury.

Burke-Gaffney A, Svermova T, Mumby S, Finney SJ, Evans TW - PLoS ONE (2014)

Bottom Line: There was a positive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively.Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135).When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16; AKIN: 6546 pg/ml, IQR 5025-8079, n = 6; vs. 3727 pg/ml, IQR 1962-3727, n = 26) subjects.

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology, Cardiovascular Sciences, National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, London, United Kingdom.

ABSTRACT

Objective: Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB). Roundabout protein 4 (Robo4), an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI), after cardiac surgery.

Methods: Patients (n = 32) undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4 concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma and endothelial markers of inflammation [interleukin (IL) -6, -8, -10: von Willibrand factor (vWF) and angiopoeitin-2 (Ang-2)] and the AKI marker, neutrophil gelatinase-associated lipocalin (NGAL), were also measured by ELISA.

Results: Plasma Robo4 increased significantly (p<0.001) from pre-operative levels of 2515 ± 904 pg/ml to 4473 ± 1915 pg/ml, 2 h after surgery; and returned to basal levels (2682 ± 979 pg/ml) by 24 h. Plasma cytokines, vWF and NGAL also increased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was a positive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively. Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135). When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16; AKIN: 6546 pg/ml, IQR 5025-8079, n = 6; vs. 3727 pg/ml, IQR 1962-3727, n = 26) subjects.

Conclusion: Plasma Robo4 levels are increased, transiently, following cardiac surgery requiring CPB; and higher levels in patients with AKI suggest a link between endothelial dysregulation and onset of AKI.

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Plasma Robo4 levels in patients with or without AKI according to AKI Network classification.Plasma levels of Robo4 in patients, 2 h post-cardiac surgery requiring cardiopulmonary bypass with or without acute kidney injury (AKI); assigned according to AKI Network clinical classification. Data presented as median, IQR concentrations (pg/ml) of Robo4 (n = 26, non-AKI and n = 6, AKI).
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pone-0111459-g003: Plasma Robo4 levels in patients with or without AKI according to AKI Network classification.Plasma levels of Robo4 in patients, 2 h post-cardiac surgery requiring cardiopulmonary bypass with or without acute kidney injury (AKI); assigned according to AKI Network clinical classification. Data presented as median, IQR concentrations (pg/ml) of Robo4 (n = 26, non-AKI and n = 6, AKI).

Mentions: Robo4 was significantly (p = 0.0073) greater in the patient group with plasma levels of NGAL of >150 ng/ml (5350±2191 ng/ml, n = 16), than in the group with NGAL levels <150 ng/ml (3595±1068 pg/ml, n = 16; Fig. 2). Likewise, when grouped based on urinary NGAL, Robo4 levels were also significantly different (AKI: 6335 ng/ml, IQR 5025–7771, n = 6; vs non-AKI: 3723 ng/ml, IQR 2840–5028, p = 0041). When patients were grouped according to AKIN guidelines, there was a significant difference (p = 0.003) between AKI (6546 pg/ml, IQR 5025–8079; n = 6) and non-AKI patients (3727 pg/ml, IQR 1962–3727; n = 26; Fig. 3).


Raised plasma Robo4 and cardiac surgery-associated acute kidney injury.

Burke-Gaffney A, Svermova T, Mumby S, Finney SJ, Evans TW - PLoS ONE (2014)

Plasma Robo4 levels in patients with or without AKI according to AKI Network classification.Plasma levels of Robo4 in patients, 2 h post-cardiac surgery requiring cardiopulmonary bypass with or without acute kidney injury (AKI); assigned according to AKI Network clinical classification. Data presented as median, IQR concentrations (pg/ml) of Robo4 (n = 26, non-AKI and n = 6, AKI).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216014&req=5

pone-0111459-g003: Plasma Robo4 levels in patients with or without AKI according to AKI Network classification.Plasma levels of Robo4 in patients, 2 h post-cardiac surgery requiring cardiopulmonary bypass with or without acute kidney injury (AKI); assigned according to AKI Network clinical classification. Data presented as median, IQR concentrations (pg/ml) of Robo4 (n = 26, non-AKI and n = 6, AKI).
Mentions: Robo4 was significantly (p = 0.0073) greater in the patient group with plasma levels of NGAL of >150 ng/ml (5350±2191 ng/ml, n = 16), than in the group with NGAL levels <150 ng/ml (3595±1068 pg/ml, n = 16; Fig. 2). Likewise, when grouped based on urinary NGAL, Robo4 levels were also significantly different (AKI: 6335 ng/ml, IQR 5025–7771, n = 6; vs non-AKI: 3723 ng/ml, IQR 2840–5028, p = 0041). When patients were grouped according to AKIN guidelines, there was a significant difference (p = 0.003) between AKI (6546 pg/ml, IQR 5025–8079; n = 6) and non-AKI patients (3727 pg/ml, IQR 1962–3727; n = 26; Fig. 3).

Bottom Line: There was a positive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively.Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135).When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16; AKIN: 6546 pg/ml, IQR 5025-8079, n = 6; vs. 3727 pg/ml, IQR 1962-3727, n = 26) subjects.

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology, Cardiovascular Sciences, National Heart and Lung Institute Division, Faculty of Medicine, Imperial College London, London, United Kingdom.

ABSTRACT

Objective: Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB). Roundabout protein 4 (Robo4), an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI), after cardiac surgery.

Methods: Patients (n = 32) undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4 concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma and endothelial markers of inflammation [interleukin (IL) -6, -8, -10: von Willibrand factor (vWF) and angiopoeitin-2 (Ang-2)] and the AKI marker, neutrophil gelatinase-associated lipocalin (NGAL), were also measured by ELISA.

Results: Plasma Robo4 increased significantly (p<0.001) from pre-operative levels of 2515 ± 904 pg/ml to 4473 ± 1915 pg/ml, 2 h after surgery; and returned to basal levels (2682 ± 979 pg/ml) by 24 h. Plasma cytokines, vWF and NGAL also increased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was a positive, significant correlation (r = 0.385, p = 0.0298) between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively. Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h) plasma NGAL and Robo4 (r = 0.4322, p = 0.0135). When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN) clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively) in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16; AKIN: 6546 pg/ml, IQR 5025-8079, n = 6; vs. 3727 pg/ml, IQR 1962-3727, n = 26) subjects.

Conclusion: Plasma Robo4 levels are increased, transiently, following cardiac surgery requiring CPB; and higher levels in patients with AKI suggest a link between endothelial dysregulation and onset of AKI.

Show MeSH
Related in: MedlinePlus