Early osteopontin levels predict mortality in patients with septic shock

Carbone, Federico; Bonaventura, Aldo; Vecchiè, Alessandra; Meessen, Jennifer; Minetti, Silvia; Elia, Edoardo; Ferrara, Daniele; Ansaldo, Anna Maria; Tulli, G; Guarducci, Diletta; Rossi, Nicola De; Bona, Francesco De; Ferrari, Marta; Caironi, Pietro; Latini, Roberto

doi:10.1016/j.ejim.2020.04.035

Cited by 16 publications

(20 citation statements)

References 29 publications

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“…All these conditions are highly associated with multiorgan failure, in particular AKI and ALI or its most severe form acute respiratory distress syndrome (ARDS). This suggests that OPN upregulation represents a conserved response to tissue injury in different organs and might indeed link circulating OPN to secondary organ failure in general, as is suggested by various studies of serum OPN as a biomarker of multiorgan failure mortality in humans 32,47,51 . Consistent with this, one other study in mice connected OPN to lung injury after intestinal ischemia 55 .…”

Section: Discussionmentioning

confidence: 69%

“…However, in contrast to our study, OPN in this model was found upregulated in both the ischemic gut and the remotely injured lung, not allowing the investigators to identify the source of serum OPN elevations or conclusively determine that circulating OPN was indeed involved in inducing lung injury. Broadening the putative relevance of our study is the fact that remote organ effects after AKI can also be detected in a number of other organs, including the heart and brain 13 .OPN serum levels are elevated in the systemic inflammatory response syndrome (SIRS) and sepsis 52 and predict mortality in patients with sepsis and multiorgan failure 31,32 .…”

Section: Discussionmentioning

confidence: 83%

“…Serum OPN protein levels have been studied as a biomarker of severity of disease in patients with multiorgan failure, often including AKI and ALI 31,32 . Whether serum OPN levels are also elevated in patients with AKI prior to development of multiorgan failure is not known.…”

Section: Opn Is Upregulated In Kidneys But Not Lungs During Aki-induced Alimentioning

confidence: 99%

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Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Khamissi¹,

Ning²,

Kefaloyianni³

et al. 2021

Preprint

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Multiorgan failure is devastating, and its mechanisms and mediators are not clear. Tissue injury in one organ appears to trigger disease in remote organs. Kidney and lung are frequently affected, such as when acute kidney injury (AKI) causes acute lung injury (ALI), a frequent clinical condition with high mortality. Here we identify factors secreted from the injured kidney that cause acute lung injury. We developed a murine model mimicking the generation of respiratory failure following acute kidney injury. To identify interorgan crosstalk mediators involved, we performed scRNAseq of mouse kidneys and lungs after AKI. We then applied ligand-receptor (L-R) pairing analysis across cells residing in kidney (ligands) or lung (receptors) to identify kidney-released circulating osteopontin (OPN) as a novel mediator of AKI-induced ALI (AKI-ALI). OPN release very early after AKI largely from tubule cells triggered neutrophil and macrophage infiltration into lungs associated with endothelial leakage, interstitial edema, and functional impairment. Pharmacological or genetic inhibition of OPN prevented AKI-ALI. Transplantation of ischemic wt kidneys into wt mice caused AKI-ALI, while transplantation of ischemic OPN-global-knockout kidneys failed to induce lung endothelial leakage and AKI-ALI, identifying circulating kidney-released OPN as sufficient to cause AKI-ALI in vivo. We show that AKI in humans results in elevations in OPN levels in the serum. Increased serum OPN levels in patients with multiorgan failure have been shown to positively correlate with reduced kidney function, respiratory failure, and mortality. Thus, our results identifying OPN as a mediator of AKI-ALI may have important therapeutic implications in human AKI-ALI and multiorgan failure.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 83%

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Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Khamissi¹,

Ning²,

Kefaloyianni³

et al. 2021

Preprint

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“…Multiorgan dysfunction during sepsis and its evolution towards septic shock are critically influenced by dysregulation of the host's inflammatory response [1]. Different biomarkers have been studied to keep track of these alterations, such as Creactive protein (CRP), procalcitonin, osteopontin and pentraxin 3 (PTX3) [2][3][4]. Several signaling cascades are involved in the defensive mechanisms against infections with a central role played by cholesterol and lipids [5].…”

Section: Introductionmentioning

confidence: 99%

PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study

et al. 2020

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Background Pro‐protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low‐density lipoprotein receptor re‐uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. Methods Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman’s coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28‐ and 90‐day mortality. Results Median plasma PCSK9 levels were 278 [182–452] ng mL−1 on day 1. PCSK9 correlated positively with PTX3 at the three time‐points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28‐ and 90‐day mortality rate as compared to other quartiles. Conclusion In our sub‐analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

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“…Circulating biomarkers might help understand the underlying inflammatory mechanisms in patients with severe sepsis and septic shock and select the most appropriate monitoring strategies and treatments 1 . A wealth of biomarkers have been investigated, 2‐6 and some of them, such as C‐reactive protein (CRP) and procalcitonin, are routinely used in clinical practice 7,8 …”

Section: Introductionmentioning

confidence: 99%

The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial

Bonaventura

Carbone

Vecchiè

et al. 2020

Eur J Clin Investigation

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Background: Inflammatory biomarkers are useful in detecting patients with sepsis. The prognostic role of resistin and myeloperoxidase (MPO) has been investigated in sepsis. Materials and Methods: Plasma resistin and MPO were measured on days 1, 2 and 7 in 957 patients enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. The association between resistin and MPO levels on day 1, 2 and 7 and 90-day mortality was assessed. Results: Plasma resistin and MPO concentrations were higher at day 1 and decreased until day 7. Both biomarkers were positively correlated with each other and with physiological parameters. Higher levels of resistin and MPO on day 1 were associated with the development of new organ failures. Patients experiencing death at 90 days showed higher levels of resistin and MPO compared with survivors. At day 1, only MPO in the 4th quartile (Q4), but not resistin, was found to predict 90-day death (adjusted hazard ratio [aHR] 1.55 vs Q1). At day 2, resistin in the Q3 and Q4 2 of 13 | BONAVENTURA ET Al.

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Early osteopontin levels predict mortality in patients with septic shock

Cited by 16 publications

References 29 publications

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study

The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial

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