NGAL As An Aid for the Diagnosis of Acute Kidney Injury in Intensive Care

AKI is a common and severe complication in critically ill patients, which is associated with
increased morbidity and mortality as well as high costs of medical care.

Despite efforts to standardize the definition and classification of AKI, there is still
inconsistency in the application of the criteria and the limitations of serum creatinine and
urine output for detecting AKI is generally recognized by the medical community. In the
future, biomarkers of renal cell injury may identify additional patients with AKI and may
identify the majority of patients at an earlier stage.

NGAL (neutrophil gelatinase-associated lipocalin, lipocalin-2, siderocalin) is such a
biomarker. It is a small protein expressed in neutrophils and certain epithelia, including
the renal tubules. Renal expression of NGAL is dramatically increased in kidney injury from
a variety of causes, and NGAL is released into both urine and plasma. NGAL levels rise
within two hours of the insult, making NGAL an early and sensitive biomarker of kidney
injury.

Due to the heterogeneous implementation of AKI definitions and classifications, a uniform
definition will be applied to this investigation, to ensure comparative results between the
enrollment sites.

The aim of the study is to validate the assigned NGAL cutoff value by comparing to clinical
diagnosis of AKI as determined by current clinical practice in the US.

The study sites will enroll consecutive patients meeting the criteria below in an ICU or
critical care setting. Patients are given standard clinical care and lab-work. Each day, one
additional urine and two additional plasma samples will be drawn and frozen. These
additional samples are shipped to Sponsor for retrospective NGAL measurements.

The duration of each subject´s participation will be until discharge from the ICU, or for a
maximum 8 days, whichever comes first. In addition serum creatinine values will continue to
be collected manually from the hospital data system for 48 hours after discharge from the
ICU. (If subject has been in ICU for 8 or more days, the follow up values are collected
while the patient is still in the ICU).

250 subjects will be enrolled in total at the three investigator sites. At least 40 patients
must be enrolled at each site.

The NGAL value will be matched to the "clinical diagnosis" of acute kidney injury (AKI) as
specified by KDIGO® guidelines. The clinical diagnosis will be assigned by a three-person
adjudication panel based on the entries in the eCRF by the investigators. Adjudicators are
blinded for investigation site, AKI-diagnosis by treating physician, and NGAL values.

A comparison of AKI diagnosis based on the cutoff value 250 ng/mL and clinical diagnosis as
assigned by the majority of the adjudication panel will be conducted.

Primary endpoints:

- Sensitivity of the NGAL test will be estimated as the proportion of patients with an
observed NGAL value above or equal to 250 ng/ml among patients classified as having
AKI, and.

- Specificity of the NGAL test will be estimated as the proportion of patients with an
observed NGAL value below 250 ng/ml among patients classified as not having AKI

Inclusion Criteria:

- Admission to intensive care unit

- Informed consent

- Age ≥ 18 years.

Exclusion criteria:

- History of nephrectomy, renal transplantation and/or renal replacement therapy
initiated before admission

- Males and females aged 17 years or below