Biomarkers for Acute Kidney Injury

Acute Kidney Injury (AKI), also known as Acute Renal Failure (ARF), is an advanced stage of kidney damage where functional and structural abnormalities develop in the kidneys. These abnormalities adversely affect the overall functioning of the kidneys. In normal conditions, the kidneys filter waste products from the blood and excrete them via the urine. In AKI, the function of the kidneys is severely affected which leads to retention of metabolic waste products¹ .
AKI can be caused by kidney diseases, as well as, diseases originating in other organ systems of the body. Hematologic cancers, sepsis, and acquired immunodeficiency syndrome (AIDS) are common extra-renal (outside of the kidneys) causes of AKI. It is a common condition in critically ill patients and is associated with a high risk of mortality².

In clinical practice, the standard tests used to diagnose and manage AKI include measurement of serum creatinine (Cr) and blood urea nitrogen (BUN). These laboratory tests are non-specific and insensitive. Moreover, these tests can detect AKI only after substantial kidney injury has occurred. This delay in the diagnosis of AKI can prevent timely patient management and treatment, which can cause accelerated progression to end-stage renal disease (ESRD) and even congestive heart failure. In such a scenario, there is great need of sensitive, specific, and reliable biomarkers that can rapidly detect AKI and prevent life-threatening complications^1,2 .

Which Biomarkers Exist for Acute Kidney Injury?

Currently available biomarkers for AKI include the following³ :

• Neutrophil gelatinase-associated lipocalin (NGAL): This is a strong indicator of kidney injury. Levels of NGAL within the kidneys is significantly elevated following ischemic (low blood supply) kidney injury or nephrotoxic kidney injury. Elevated levels of NGAL can be detected in the urine as early as 3 hours after kidney injury. The concentration of NGAL usually peaks 6 hours after AKI.
• Kidney injury molecule- 1 (KIM 1): This is a transmembrane protein which in normal conditions has a low expression on the kidneys. After ischemia-reperfusion injury to the kidneys, the levels of KIM 1 are elevated. KIM 1 is also thought to play a role in renal recovery and tubular regeneration (kidney tubules) after AKI.
• IL-18: This is a pro-inflammatory cytokine which is elevated following different types of AKI, such as ischemia-reperfusion injury, cisplatin-induced kidney injury (drug toxicity), and glycerol injection.
• L-FABP: This is a gene expressed in the renal cortex. Elevated levels of L-FABP can be detected immediately postoperatively in patients undergoing cardiac surgery who go on to develop AKI. The levels of L-FABP peak after 6 hours. L-FABP can be used to guide clinical intervention in patients at risk of AKI.

suPAR: This is a marker of chronic inflammation, and is also an earlier predictor of kidney disease compared to those mentioned above. Interestingly, according to a publication in NEJM in 2020, suPAR may not only reflect development of AKI but may even cause it⁴ .

The following studies further support suPAR as a biomarker for acute kidney injury:

• A prospective observational study published in 2018 in the journal BMC Nephrology studied the effectiveness of suPAR in critically ill patients with AKI. As per the study reveals, suPAR is a better marker for infection than CRP⁵ .
• As per a study published in 2019 in Circulation, higher suPAR levels predicted risk of post-procedural AKI in patients undergoing cardiac surgery. The study suggested that suPAR could be used as a prognostic marker for AKI and can be used for AKI prevention in the future⁶ .
• Another study published in 2017 supported the use of suPAR as a predictive biomarker for AKI in patients undergoing cardiac surgery⁷ .