Low-dose hydrocortisone during severe sepsis: Effects on microalbuminuria

Rinaldi, Simone; Adembri, Chiara; Grechi, Serenèlla; Gaudio, Angelo Raffaele De

doi:10.1097/01.ccm.0000233872.04706.bb

Cited by 77 publications

(78 citation statements)

References 39 publications

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“…Several lines of clinical study showed that patients underwent septic injury manifested albuminuria (6,25,28), but its mechanisms are not fully understood. Using LPS-treated mice as a septic model, we demonstrated the reciprocal relationship between glomerular nephrin expression and albuminuria in the albuminuric phase (i.e., 36 h post-challenge):…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial wall components-such as LPS and histone-related proteins-are known to elicit proteinuria (1,32,33,35). These studies provide a clue to explain albuminuria occurred in septic patients (6,25,28), or in subjects after Streptococcal infection in children (13), but the molecular basis has not been fully understood. Herein, we proposed the molecular cascades leading to albuminuria through cytokine storm: (i) direct inhibitory effects of IL-1β on nephrin production in podocytes; and (ii) indirect actions of cytokine storm toward nephrin loss via decrease in nuclear WT1 (i.e., loss-of-function).…”

Section: Wt1 Transfer Into Cytoplasm In Septic Kidneymentioning

confidence: 99%

“…The infectious components (including bacterial cell walls) function as foreign ligands of toll-like receptors, and systemic inflammation elicits thrombosis and eventually multiple organ failure (4,26). Furthermore, albuminuria is also a common event during septic diseases (6,25,28), along with inflammatory responses. For example, lipopolysaccharide (LPS) of Escherichia coli, or histone-like protein of Streptococcal pyogenesis, often triggers albuminuria and glomerular nephritis (1,32,33), and this is associated with over-production of pro-inflammatory cytokines by activated macrophages (10,22).…”

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The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria during the experimental sepsis in mice

2010

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Sepsis is induced by infectious challenges, and septic organ failure often occurs under local and systemic inflammation. Albuminuria is also evident during sepsis, but little is known about the molecular basis of septic albuminuria. Using lipopolysaccharide (LPS)-treated mice as a sepsis model, we found that the loss of nephrin, a key component for maintaining podocyte slit diaphragm, became evident in accordance with the onset of albuminuria, especially 36 h post-LPS challenge (i.e., albumiuric stage). Likewise, nephrin mRNA levels were decreased to 13% of saline-treated mice. Such a transcriptional suppression of nephrin was associated with the loss of nucleus-localized Wilms tumor-1 (WT1), a transcriptional factor for up-regulating nephrin gene. Thereafter, urinary albumin levels were decreased in mice between 72 and 96 h post-LPS challenge (i.e., recovery-stage). Notably, nuclear localization of WT1 seemed to be normalized, and nephrin mRNA and protein levels returned near the basal level 72 h post-LPS challenge. During LPS-mediated sepsis, there was a transient increase in blood interleukin-1β, a suppressor of nephrin production in podocytes. Therefore, down-regulation of nephrin by the loss in nuclear WT1, along with hyper-cytokinemia, may underlie the mechanisms by which albuminuria is induced by infectious stresses.Septic syndrome is elicited by infectious agents of bacteria, virus, and fungus. The infectious components (including bacterial cell walls) function as foreign ligands of toll-like receptors, and systemic inflammation elicits thrombosis and eventually multiple organ failure (4, 26). Furthermore, albuminuria is also a common event during septic diseases (6,25,28), along with inflammatory responses. For example, lipopolysaccharide (LPS) of Escherichia coli, or histone-like protein of Streptococcal pyogenesis, often triggers albuminuria and glomerular nephritis (1,32,33), and this is associated with over-production of pro-inflammatory cytokines by activated macrophages (10,22). However, it is still unclear how sepsis-induced albuminuria is linked with an increase in pro-inflammatory cytokines (i.e., cytokine storm). Recent merging evidences provide a central dogma that glomerular podocytes have a key function to prevent the onset of albuminuria (2, 16, 31). Podocytes form foot processes, highly dynamic cellular extensions that are connected by slit diaphragm. As an important protein for podocytes, nephrin (encoded by NPHS1 gene) is well known (16,31). Nephrin is a transmembrane protein of the

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Section: Discussionmentioning

confidence: 99%

Section: Wt1 Transfer Into Cytoplasm In Septic Kidneymentioning

confidence: 99%

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The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria during the experimental sepsis in mice

2010

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“…Так, прием глюкокор-тикоидов существенно не влиял на уровень ПК. В то же время имеются данные о том, что при длитель-ном использовании высоких доз глюкокортикоидов О б з о р ы уровень ПК имеет тенденцию к снижению [38,[42][43][44][45][46]. Иммуносупрессоры и некоторые биологические пре-параты (ингибиторы фактора некроза опухоли α, ин-терлейкин 6, ритуксимаб) также не оказывали влияния на уровень ПКТ крови [43,47,48].…”

Section: болезнь стилла взрослыхunclassified

Procalcitonin Testing in Rheumatology

Буханова¹,

Белов²,

Тарасова³

et al. 2017

Klinicist

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“…Additional file 1: Summary tables of included and excluded study characteristics [47][48][49][50][51][52][53][54][55][56][57][58][59][60] …”

Section: Additional Filesmentioning

confidence: 99%

Corticosteroid Treatment in Critically Ill Patients

Lee¹,

Ryu²

2017

J Neurocrit Care

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Background: Multiple corticosteroids and treatment regimens have been used as adjuncts in the treatment of septic shock. Qualitative and quantitative differences exist at cellular and tissular levels between the different drugs and their patterns of delivery. The objective of this study was to elucidate any differences between the drugs and their treatment regimens regarding outcomes for corticosteroid use in adult patients with septic shock. Methods: Network meta-analysis of the data used for the recently conducted Cochrane review was performed. Studies that included children and were designed to assess respiratory function in pneumonia and acute respiratory distress syndrome, as well as cross-over studies, were excluded. Network plots were created for each outcome, and all analyses were conducted using a frequentist approach assuming a random-effects model. Results: Complete data from 22 studies and partial data from 1 study were included. Network meta-analysis provided no clear evidence that any intervention or treatment regimen is better than any other across the spectrum of outcomes. There was strong evidence of differential efficacy in only one area: shock reversal. Hydrocortisone boluses and infusions were more likely than methylprednisolone boluses and placebo to result in shock reversal. Conclusions: There was no clear evidence that any one corticosteroid drug or treatment regimen is more likely to be effective in reducing mortality or reducing the incidence of gastrointestinal bleeding or superinfection in septic shock. Hydrocortisone delivered as a bolus or as an infusion was more likely than placebo and methylprednisolone to result in shock reversal.

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Low-dose hydrocortisone during severe sepsis: Effects on microalbuminuria

Abstract: Low-dose hydrocortisone seems to reduce MACR and serum C-reactive protein but not procalcitonin in patients with severe sepsis. Further studies are needed to confirm these results and to understand the underlying molecular mechanisms.

Cited by 77 publications

References 39 publications

The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria during the experimental sepsis in mice

The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria during the experimental sepsis in mice

Procalcitonin Testing in Rheumatology

Corticosteroid Treatment in Critically Ill Patients

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