Diagnostic accuracy of urine biomarkers for acute kidney injury after major surgery

Acute kidney injury (AKI) is defined as a sudden decrease of renal function
with a decline in glomerular filtration rate. AKI encompasses a broad spectrum
of different kinds and severity of renal impairment. Possible causes of AKI are
ischemia, exposure to nephrotoxic agents, sepsis, volume depletion with reduced
renal perfusion, urinary obstruction, glomerulonephritis and acute interstitial
nephritis. AKI occurs in 5-15% of all hospital admissions and in 20-45% of
patients after major surgery. AKI is associated with short-term adverse events
such as increased in-hospital mortality and length of hospital stay. AKI is
also associated with long-term mortality and end-stage renal disease, even in
patients with initial recovery to baseline serum creatinine concentrations. The
severity of AKI is proportional to the short-term mortality risk, but even
small increases of creatinine are associated with increased mortality and
morbidity. Loss of kidney function can be diagnosed by an increase of serum
creatinine concentration and a decrease of urine production. An international
consensus definition of acute kidney injury is provided by the Kidney Disease
Improving Global Outcomes initiative. Acute kidney injury after major surgery
is common and associated with adverse short-term and long-term outcomes. Early
detection and treatment of AKI might improve outcomes. The current diagnosis of
AKI is based on the gradual accumulation of serum creatinine over the first
days after the renal insult, and is therefore not useful for the early
detection of AKI. Over the past decade, several groups have identified urine
biomarkers for early detection of AKI. These urine biomarkers have mostly been
studied in small groups of patients admitted to the intensive care unit or
undergoing cardiac surgery and have generally not been replicated to validate
the initial findings.

In the current study, we intend to study the diagnostic accuracy of promising
urine biomarkers for early detection of acute kidney injury in patients
undergoing major general surgery. The study is designed to validate earlier
findings in a large group of patients, to extend the use of these biomarkers to
general surgery and to select the biomarkers with greatest diagnostic accuracy
for clinical use. If the diagnostic accuracy of the biomarkers is sufficiently
high, the markers could be used for earlier diagnosis and treatment of AKI.

This is a predictive diagnostic study. The study group consists of patients
undergoing elective major surgery in two hospitals: Maastricht University
Medical Center and Zuijderland Ziekenhuis at Heerlen and Geleen. The
concentration of urine biomarkers of acute kidney injury and level of serum
creatinine will be measured on arrival at the postoperative recovery unit. In
the 48 hours after start of surgery, changes in serum creatinine concentrations
from baseline will be recorded to establish the gold standard definition of
acute kidney injury. The diagnostic accuracy of the biomarkers for early
detection of acute kidney injury is assessed as the area under the receiver
operating characteristic curves. Long-term decline of renal function will be
measured at one year after surgery.

The patient will have two extra blood sample collections as intervention.

Patients will be exposed to the negligible additional risk of one or two
venepunctures (5mL of blood). The timed urine collection and venepuncture on
arrival at the postoperative recovery unit will take 15 minutes of time. The
venepuncture at 10 to 14 months after surgery will take approximately 15
minutes of time (excluding traveling time). Patients will not experience direct
benefits from participating in this study. However, identification of accurate
early biomarkers of acute kidney injury may improve treatment of this condition
for future patients.