This Scientific Short is part of a series based on Guidance Documents published by the Academy. To read the full guidance click here.

Acute kidney injury (AKI) is a sudden decline in kidney function, often occurring within two days or less. It can be triggered by certain medications and medical procedures, posing serious health risks like irreversible kidney damage and even death. AKI affects about 15% of hospitalized patients and up to 50% of those in intensive care units. The current way we define and detect AKI has issues that needed addressing.

In 2012, the nonprofit organization KDIGO introduced guidelines for managing AKI, defining it based on changes in the kidney biomarkers serum creatinine and urine output.1 For creatinine, they set a threshold of a 0.3 mg/dL increase within 48 hours or a 50% increase within 7 days. Urine output less than 0.5 mL/kg/h for 6 hours also signals AKI, but it's not as widely used as serum creatinine. The problem is that the creatinine-based definition lacks a solid biological or analytical foundation, as it was consensus-based and consensus group did not include clinical laboratory experts. Unsurprisingly, this KDIGO definition led to false positives, especially in patients with creatinine values over 1.5 mg/dL, and delayed AKI detection in those with creatinine below 1.0 mg/dL, particularly in children with naturally low creatinine levels.2 This led many to question the reliability of creatinine as an AKI marker. So, academics turned their attention to evaluating novel structural biomarkers that can detect AKI earlier than creatinine, like urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP2].[IGFBP7]).

To address this and other gaps in the laboratory investigation of AKI, a group of nephrology and laboratory medicine experts were convened by the ADLM Academy (formely AACC Academy) to develop a guidance document that addresses these issues.2 Focusing on the problems with the current definition of AKI, we turned to the concept of "reference change value" (RCV) in laboratory medicine. The RCV helps determine what changes in an analyte, like creatinine, are significant. It is calculated based on two factors: analytical variation and intra-individual biological variation. These values may vary by method and concentration range.

For creatinine levels equal to or greater than 1 mg/dL, we found that a 20% change is considered highly significant. For levels less than 1 mg/dL, a change of 0.2 mg/dL (~20 umol/L) is highly significant. This concept was named the "20/20 AACC AKI definition" to emphasize the 20% or 20 umol/L (0.2 mg/dL) change.2 These changes were separately linked to poor clinical outcomes in the short and long term, so there is enough clinical evidence from large studies to support their use. We also evaluated the utility of urinary [TIMP2].[IGFBP7] and did not find enough evidence to support its clinical use.

In conclusion, the current definition of AKI has shortcomings, and the 20/20 AACC AKI definition offers a more evidence-based and adaptable approach for detecting AKI using creatinine levels. This refined approach has the potential to improve AKI diagnosis and patient care.

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References

  1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138.
  2. El-Khoury JM, Hoenig MP, Jones GRD, et al. AACC Guidance Document on Laboratory Investigation of Acute Kidney Injury. J Appl Lab Med. 2021;6:1316-1337