Clinical effectiveness

For the differentiation of severity of acute kidney injury (AKI)

Key words:AKI (Acute Kidney Injury), Cardiorenal Syndrome

ROC analysis of 14-day mortality rate


(partially modified from figure 3 of article [1])

Method

Measurements were taken of L-FABP, NGAL, NAG, albumin and serum creatinine in 339 seriously ill adult patients hospitalized in the ICU, and shown in a ROC curve for the 14-day mortality rate.
※ Of the 339 patients, 14 (4.1%) died within 2 weeks of ICU hospitalization.

Results

ROC Area Under Curve (AUC-ROC)
L-FABP0.896
NGAL 0.827
NAG0.664
Albumin0.717
Serum creatinine0.733

Urinary L-FABP can give a highly precise to predict mortality in patients with drug-induced renal failure, sepsis and multiple organ failure, etc., at the ICU hospitalization.

In March, 2012, the KDIGO Clinical Practice Guideline for Acute Kidney Injury 1 guideline relating to the treatment of AKI (Acute Kidney Injury) was published by the KDIGO (Kidney Disease Improving Global Outcomes) foundation, which was established with the aim of developing international guidelines for kidney disease[2]. The guidelines respect the existing AKI criteria prescribed according to urine flow and serum creatinine (sCr), but also point out that, especially in cases of AKI induced by sepsis in intensive care units (ICUs), owing to concerns about decreases in the quantity of produced creatinine itself, what is required is a down-rating of AKI diagnostic performance obtained by sCr measurement, along with a biomarker for earlier AKI diagnosis.

When a new biomarker is to undergo clinical use, it is necessary for the diagnostic precision of each index to be at the standard that each country’s regulator can approve. Shown below are, from among the items for which clinical evaluations have proceeded globally in recent years, the diagnostic indexes that have received approval or are in the process of being approved as an IVD product by the FDA in the USA, the CE marking in Europe and the Ministry of Health, Labour and Welfare in Japan. The English review paper[3] that adopts these 5 items as the so-called five biomarkers of AKI is introduced in the above-mentioned KDIGO guidelines.

Neutrophil gelatinase-associated lipocalin(NGAL)
Cystatin C
Interleukin 18(IL-18)
Kidney injury molecule-1(KIM-1)
L-type fatty acid binding protein(L-FABP)

An example (3) shows the clinical data comparing the diagnosis performance of these items in Japan. Urinary L-FABP and other urinary measurements were compared for 339 ICU inpatients. 66 of 274 cases that did not have AKI when admitted to the ICU developed AKI within one week of admission. On such occasions, many urinary markers at the time of admission before development of AKI were measured, and their subsequent AKI onset prediction performance was compared. New AKI biomarkers including urinary L-FABP were able to detect AKI at ICU admission and predict later onset AKI with higher AUC-ROC values than those obtained using serum creatinine in a mixed adult ICU with heterogeneous patients.

Furthermore, for all 339 cases, many urinary markers at the time of ICU admission were measured and compared for prediction of mortality rate within two weeks of admission. In the results, urinary L-FABP had very high precision, with an ROC area under curve of 0.90, which made it clear that its diagnosis performance was significantly superior compared to NAG and albumin (figure).

Based on the above evidence, the usefulness of urinary L-FABP to “differentiate severity including therapeutic outcomes for patients with drug-induced renal injuries, sepsis and multiple organ failure, etc., where AKI has not been established” has also been approved for reimbursement IVD from the Japanese Ministry of Health, Labour and Welfare.

References

  • [1] Doi, K. et al., Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit Care Med. 39(11): 2464-2469, 2011. PubMed
  • [2] KDIGO(Kidney Disease: Improving Global Outcomes) http://www.kdigo.org/clinical_practice_guidelines/AKI.php
  • [3] Moore, E., et al., Biomarkers of acute kidney injury in anesthesia, intensive care and major surgery: from the bench to clinical research to clinical practice. Minerva Anestesiol. 76(6): 425-440, 2010. PubMed

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For nonclinical safety evaluation

Urinary L-FABP kits for Rat, Dog, Cat, Monkey and Pig are available for the purpose of monitoring drug nephrotoxicity and drug effectiveness.
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