Effects of Alkaline Phosphatase on Renal Function in Septic Patients

Septic shock is the most common cause of death in patients requiring intensive care. The kidney is one of the first organs to fail, stressing the importance to search for clinical interventions that may protect the kidneys during sepsis. Alkaline phosphatase functions as a host defence molecule and is present in many cells and organs (e.g. intestine, placenta, liver, kidney and bone). Alkaline phosphatase has a dual mode of action. First, it binds to and, subsequently, dephosphorylates lipopolysaccharide (LPS). Second, the enzymatic reaction product monophosphoryl-LPS is a non-toxic substance for mammals which acts as a partial antagonist on the LPS receptor complex. In several animal studies, administration of alkaline phosphatase attenuates the inflammatory response and reduces mortality. It is unknown whether these results can be extrapolated to septic patients . We studied the effects of alkaline phosphatse administration on kidney damage and function in patients with severe sepsis or septic shock.

Inclusion Criteria: Written informed consent Proven or suspected Gram-negative bacterial infection Two out of four Systemic Inflammatory Response Syndrome (SIRS) criteria existing for less than 24 h Acute onset of end-organ dysfunction in the preceding 12 h Exclusion Criteria: Prior therapy with alkaline phosphatase Known allergy for cow milk Probable death within 24 h Chronic renal failure requiring hemodialysis or peritoneal dialysis Acute pancreatitis with no established source of infection HIV seropositive Pregnant or lactating Confirmed Gram-positive or fungal sepsis Treatment with immunosuppressants including high doses of glucocorticosteroids