Rescue Alkaline Phosphatase In Defense against all cause Acute Kidney Injury

Acute Kidney Injury (AKI) is a frequent complication in hospitalized patients
and contributes to a high mortality and morbidity during hospitalization but
also to long term morbidity such as chronic kidney disease (CKD) with
cardiovascular complications. Risk of long term complications after AKI is
increased when an AKI period lasts for seven days or longer, which is when AKI
turns into acute kidney disease (AKD). Its immediate and long lasting risk to
patient health, makes that AKI has a heavy burden on society and public health.
Intrarenal inflammation with leukocyte recruitment and tissue infiltration,
with reciprocal influence on endothelial and tubular cell damage, are key
mediators of all cause AKI. With pharmacological interventions for AKI lacking,
only supportive care or in extreme cases, replacement therapy, are used in
treatment of patients suffering from AKI. However, advancements are made in
studying the renoprotective effects of exogenous alkaline phosphatase (AP)
which could modulate kidney injury through anti-inflammatory and protective
effects against cell damage and microcirculatory impairment.

To study the potential renoprotective effects of supplementation of alkaline
phosphatase in hospitalized patients with AKI

A double blind randomized, placebo-controlled trial

The intervention group will be treated with a bolus of 1000 international units
(IU) bovine rescue alkaline phosphatase (bRESCAP manufactured by Alloksys Life
Sciences), followed by continuous infusion 29,000IU of AP for a total of three
days resulting in a total infusion of 30,000 IU. Treatment will be initiated
within 24 hours after diagnosis of AKI.

Most patients with AKI already have an indication for intravenous access as
part of standard of care. A second intravenous access site will be required
for the study agent/placebo. The proposed effect of alkaline phosphatase is to
modulate the immune response responsible for acute kidney injury. There is only
a small theoretical risk that this protein-based drug causes an allergic
reaction. In various placebo controlled trials in sepsis and cardiothoracic
patients, no adverse effects were registered. In a cardiothoracic cohort the
morbidity and mortality were higher in the placebo arm than in the treatment
arm. Another study which was conducted with a human recombinant AP used in
sepsispatients also showed decrease in adverse events.

Blood and urine samples are collected from day 0 - 7 or in case of release from
the hospital before day 7, samples will be collected until the day of release.
In the follow-up period further blood and urine samples, including a 24hour
urine collection, will be collected at day 28 and 90 and at one year. Blood
samples will be collected via an intravenous or intra-arterial catheter (in
case of ICU stay) or together with routine blood samples as part of normal AKI
follow-up (standard care). No extra punctures will be necessary. A total of 80
ml of extra blood will be withdrawn during the study period.
Extra study-related site visits will be planned at day 28 and 90 and at 12
months after AKI was diagnosed. At 3 months, gold standard glomerular
filtration rate, renal plasma flow, and renal functional reserve will be
measured by steady state iothalamate- and hippuric acid clearances in a subset
of patients.