Progress in Medical Sciences. 2030;
5(1):(47-109)
Use of Alkaline Phosphatase in Critically-Ill Patients
Zohra R. Malik* and Zareen Razaq
Abstract
Most of the patients admitted to ICU undergo organ damage, with kidney injury, liver damage, respiratory
distress and hematological derangements being the most common. We hereby present literature review
on the use of Alkaline Phosphatase (ALP) in critically ill patients with severe sepsis causing kidney injury. The
possible cause of kidney injury is inflammation and hypoxia. ALP may prevent the effects of inflammation
and hypoxia through dephosphorylation of lipopolysaccharide (LPS) and extracellular ATP, the latter
being converted to adenosine, an anti-inflammatory and tissue-protective signaling molecule [1]. The
anti-inflammatory effects of ALP on LPS-induced systemic inflammation is the proposed mechanism. ALP
detoxifies LPS and the dephosphorylated LPS is far less toxic [2]. LPS can be dephosphorylated by ALP
as shown by various experiments and this eventually improves survival [2-4]. ALP is proposed to reduce
fever and attenuate the systemic cytokine response, serum nitric oxide levels, and prevent liver and lung
damage [5, 6]. ALP is also shown through animal experiments to reduce TNF-a response, reduce IL-6
concentration, improve gas exchange during septic shock [4, 7]. An animal experiment was conducted,
which showed if we give an ALP inhibitor (L-phenylalanine), the serum LPS levels significantly increase,
causing the pathogenesis of septic shock. TLR (toll-like receptor), plays an important role in pathogen
recognition and activation of the innate immunity. ALP seems to interact with the LPS-TLR pathway. The
LPS induces an increase in NF-kB activity which seems to be attenuated in the cells that were pre-treated
with ALP. The pro-inflammatory molecule, Resolvin-E1 reduces LPS induced NF-kB activity [8, 9]. which
is mediated through de-phosphorylation and thereby detoxification of LPS. So, if we can attenuate the
circulating LPS and cytokine levels by ALP, we can prevent renal hypoxia and AKI. Restoration of ALP might
be an evident solution to preventing kidney and other organ injury.
