Prognostic Biomarkers For Acute Kidney Injury In Liver Cirrhosis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Edinburgh
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Plasma level of kidney injury molecule-1 (KIM-1) to predict risk of developing AKI - a novel biomarker of early kidney injury
Study Overview
Brief Summary
Acute kidney injury (AKI) is a common and under-diagnosed problem in patients with liver cirrhosis, and is associated with significant illness and preventable death. Blood (serum) creatinine is the current test for kidney function, but it is an insensitive and non-specific marker in cirrhosis. The investigators hypothesise that blood (plasma) levels of kidney injury molecule-1 (KIM-1) will detect AKI earlier and predict the risk of worsening AKI in cirrhosis, thus identifying patients in need of prompt and effective treatment and improving patient outcomes. The investigators will collect blood and urine samples from cirrhosis patients admitted into hospital and study the relationship between plasma KIM-1, other diagnostic 'biomarker' tests that have recently been proposed, and patient outcomes.
Detailed Description
In 2015 the International Club of Ascites redefined AKI in cirrhosis as an increase in serum creatinine (sCr) of 26.5 µmol/L as even small increases in sCr are clinically relevant and associated with poorer outcomes. The investigators recently conducted a ward-based study of 105 cirrhotic patients admitted to the Royal Infirmary of Edinburgh (RIE) Liver Unit over a 3-month period and showed that 40% of patients developed AKI, and incidence of AKI increased with severity of cirrhosis. Increased AKI stage was associated with incrementally longer hospital stay, at an extra cost to the NHS of ~£400/day (data.gov.uk), and a greater mortality. Indeed, the mortality rate for cirrhotic patients without AKI was 6%, compared to 18%, 35% and 50% in patients with AKI stage 1, 2 and 3 respectively.
sCr is a suboptimal marker of renal dysfunction in advanced cirrhosis. Despite a normal sCr, patients may already have significant renal dysfunction, thus rendering sCr a late marker of AKI. Moreover, recurrent mild episodes of AKI, where sCr may not exceed normal laboratory limits, can lead to a gradual deterioration in baseline renal function, increased susceptibility to further acute insults and higher mortality. There is an urgent unmet need for a superior, more sensitive biomarker (a renal equivalent of troponin I (TnI)) to better identify cirrhotic patients who are most at risk of developing AKI, to aid earlier recognition of kidney impairment and allow rapid and targeted treatment. This is especially important because pre-transplant renal dysfunction in patients with cirrhosis is associated with increased morbidity and mortality after liver transplantation.
The urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP) and albumin, are significantly higher in cirrhotic patients with acute tubular necrosis (ATN), compared with pre-renal AKI and hepatorenal syndrome (HRS). Additionally, L-FABP is a marker of renal hypoxia and has been identified as a promising marker for early diagnosis of AKI, and for predicting dialysis requirement and in-hospital mortality. In view of the progressive renal vasoconstriction that occurs as cirrhosis advances, L-FABP may be a potentially relevant marker, although increased hepatic release may render it non-specific in the context of acute liver injury.
Plasma KIM-1 is a biomarker that is specific and sensitive for both acute and chronic kidney injury. KIM-1 is a transmembrane glycoprotein that is upregulated in proximal tubular cells during AKI. Work from our Group showed that early measurement of plasma KIM-1 was a more sensitive predictor of patient outcome than sCr in AKI after paracetamol-induced acute liver injury. Furthermore, in a cohort of patients with type-1 diabetes, normal sCr and normo/microalbuminuria, an elevated plasma KIM-1 level was strongly associated with risk of early progressive renal decline. However, plasma KIM-1 has never been evaluated in patients with chronic liver disease.
HYPOTHESES
Study Design
- Study Type
- Observational
- Observational Model
- Case Only
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female adult subjects over 18 years of age
- •Able to provide written informed consent and able to understand and willing to comply with the requirements of the study
- •Clinical/imaging-diagnosed or biopsy-proven liver cirrhosis of any aetiology
- •Not previously enrolled in this study on a previous admission
Exclusion Criteria
- •Those patients who do not have capacity to consent
Outcomes
Primary Outcomes
Plasma level of kidney injury molecule-1 (KIM-1) to predict risk of developing AKI - a novel biomarker of early kidney injury
Time Frame: 30 days
Plasma KIM-1 is a biomarker of kidney damage. We will measure it on admission and analyse the relationship between admission plasma KIM-1 level and risk of developing AKI during hospital stay.
Secondary Outcomes
- Rate of change in plasma level of kidney injury molecule-1 (KIM-1) between admission and day 2 to predict risk of AKI(30 days)
- Urinary kidney injury molecule-1 (KIM-1)(30 days.)
- Plasma level of kidney injury molecule-1 (KIM-1) to identify AKI on admission(30 days)
- Fractional excretion of sodium (FeNa): a measurement is taken of urine sodium and creatinine concentration, and compared to serum creatinine and sodium to analyse the degree to which the kidneys are retaining sodium(30 days)
- Plasma level of kidney injury molecule-1 (KIM-1) to identify patients with a greater risk of mortality(30 days)
- Protein-creatinine ratio (PCR): The ratio of protein to creatinine in the urine(30 days)
- Urinary liver-fatty acid binding protein (urinary L-FABP)(30 days)