Thu Jul 08 2021

Biomarkers for Acute Kidney Injury

Acute Kidney Injury (AKI), formerly known as Acute Renal Failure (ARF), represents a critical stage of kidney damage marked by significant disruptions in kidney structure and function. Under normal circumstances, kidneys efficiently filter and remove waste from the blood, excreting it through urine. However, AKI severely impairs this essential function, causing a dangerous accumulation of metabolic waste in the body1 .
AKI can stem from direct kidney ailments or result from complications in other body systems. Notably, diseases such as hematologic cancers, sepsis, and AIDS often lead to AKI, especially in patients already in critical condition. This condition elevates the risk of death significantly2.

The conventional approach to diagnosing and monitoring AKI involves measuring serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Despite their widespread use, these tests lack specificity and sensitivity. They only flag AKI after the kidneys have already sustained considerable damage. This diagnostic delay hampers the timely initiation of treatments, escalating the risk of progression to end-stage renal disease (ESRD) and potentially leading to congestive heart failure. Given these challenges, there’s an urgent need for more precise, reliable, and quick-response biomarkers. Such biomarkers could revolutionize AKI detection, facilitating prompt treatment to avert dire outcomes1,2 .

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 .

1. Gameiro J, Agapito Fonseca J, Jorge S, Lopes JA. Acute Kidney Injury Definition and Diagnosis: A Narrative Review. J Clin Med. 2018;7(10):307.
2. Sirota JC, Klawitter J, Edelstein CL. Biomarkers of acute kidney injury. Journal of Toxicology. 2011.
3. Alge JL, Arthur JM. Biomarkers of AKI: A review of mechanistic relevance and potential therapeutic implications. Clinical Journal of American Society of Nephrology. 2015. 10(1).
4. Hayek et. al. Soluble Urokinase Receptor and Acute Kidney Injury. N Engl J Med. 2020 Jan 30;382(5):416-426.
5. Hall, A., Crichton, S., Varrier, M. et al. suPAR as a marker of infection in acute kidney injury – a prospective observational study. BMC Nephrol 19, 191 (2018)
6. Hayek et.al. suPAR as a prognostic and therapeutic target in post-procedural acute kidney injury. Circulation. 2019. Vol 140: 1.
7. Mossanen JC, Pracht J, Jansen TU, et al. Elevated Soluble Urokinase Plasminogen Activator Receptor and Proenkephalin Serum Levels Predict the Development of Acute Kidney Injury after Cardiac Surgery. Int J Mol Sci. 2017;18(8):1662.

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