Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients*

Heemskerk, Suzanne; Masereeuw, Rosalinde; Moesker, O.; Bouw, Martijn P.W.J.M.; Hoeven, Johannes G. van der; Peters, Wilbert H.M.; Rüssel, Frans G. M.; Pickkers, Peter

doi:10.1097/ccm.0b013e31819598af

Cited by 127 publications

(83 citation statements)

References 26 publications

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“…Systemic IAP was well tolerated and had little to no observed toxicity or side effects. [60] Septic patients who received IAP had significant improvement in kidney function, as demonstrated by decreases in median plasma creatinine levels and creatinine clearance. [61, 62] This was associated with the IAP treated patients having a trend towards reduction in dialysis requirement and duration.…”

Section: Specific Surgical Disease Where Iap May Play a Role In Diseamentioning

confidence: 99%

Intestinal alkaline phosphatase: a summary of its role in clinical disease

Fawley

Gourlay

2016

Journal of Surgical Research

146

110

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Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP’s physiologic function, mechanisms of action and current research in specific surgical diseases.

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Section: Specific Surgical Disease Where Iap May Play a Role In Diseamentioning

confidence: 99%

Intestinal alkaline phosphatase: a summary of its role in clinical disease

Fawley

Gourlay

2016

Journal of Surgical Research

146

110

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“…Alkaline phosphatase (AP) is an endogenous enzyme that exerts detoxifying effects through dephosphorylation of endotoxins and pro-inflammatory extracellular ATP and is reduced during systemic inflammation. Heemskerk and colleagues [64] demonstrated that AP application was associated with a decreased expression of iNOS synthase in proximal tubule cells isolated from urine related to an attenuated urinary excretion of an proximal tubule injury marker. In a small, randomized trial, Pickkers et al showed that the administration of exogenous AP in septic patients improved endogenous creatinine clearance and reduced the requirement and duration of renal replacement therapy [65].…”

Section: Potential For Diagnostic and Therapeutic Targetsmentioning

confidence: 99%

Sepsis-induced acute kidney injury revisited

Zarbock

Gómez

Kellum

2014

Current Opinion in Critical Care

286

119

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Purpose of review Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis is the most common cause of AKI. Considerable evidence now suggests that the pathogenic mechanisms of sepsis-induced AKI are different from those seen in other etiologies of AKI. This review focuses on the recent advances in this area and discusses possible therapeutic interventions that might derive from these new insights into the pathogenesis of sepsis-induced AKI. Recent findings The traditional paradigm that sepsis-induced AKI arises from ischemia has been challenged by recent evidence that total renal blood flow (RBF) in is not universally impaired during sepsis, and AKI can develop in the presence of normal or even increased RBF. Animal and human studies suggest that adaptive responses of tubular epithelial cells to injurious signals are responsible for renal dysfunction. Simultaneously occurring renal inflammation and microcirculatory dysfunction further amplify these mechanisms. Summary An understanding of the pathologic mechanisms of sepsis-induced AKI emphasizes the important role of maladaptive responses to the septic insult. Preventive and therapeutic measures should be based on counteracting these maladaptive responses of tubular epithelial cells, inflammation, and microvascular dysfunction.

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“…Clinical trials showed renal protective effects of bovine intestinal alkaline phosphatase in critically ill patients with sepsis-associated acute kidney injury (AKI) [1,2]. Recently, human recombinant AP (recAP) was developed as a pharmacological attractive replacement.…”

Section: Introductionmentioning

confidence: 99%