Biomarkers Identified for Acute Kidney Injury Risk

The two novel biomarkers can detect affected patients roughly 12 to 36 hours earlier than current tests for adult patients and have been subsequently validated using a clinical assay and compared to existing markers of AKI.

Scientists at the Mayo Clinic (Rochester, MN, USA) led a multicenter study to evaluate nearly 340 biomarkers to find the two with the highest correlation to kidney injury risk. In the discovery phase, they enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the validation study, they enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment. The final analysis cohort was a heterogeneous sample of 728 critically ill patients.

Paired urine and blood samples were collected at enrollment and up to 18 hours later by standard methods and centrifuged. Biomarkers were measured with single or multiplexed immunoassays using standard enzyme-linked immunosorbent assays (ELISA). The platforms used were the Luminex 200 (Luminex; Austin, TX, USA); the MSD SECTOR Imager 6000 (Meso Scale Discovery; Gaithersburg, MD, USA), or the Astute140 Meter (Astute Medical; San Diego, CA, USA). The two biomarkers with the highest correlation to kidney injury risk were the Insulin Growth Factor Binding Protein-7 (IGFBP-7) and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2).

The investigators also examined the performance of urine TIMP-2 and IGFBP7 compared to various other markers including urine kidney-injury marker-1 (KIM-1) and urine neutrophil gelatinase-associated lipocalin (NGAL) in terms of discrimination between AKI of different severities and various non-AKI conditions including chronic kidney disease. Unlike existing markers, TIMP-2 and IGFBP7 showed clear separation between AKI and non-AKI conditions.

The authors concluded that urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are new biomarkers for AKI and perform better than existing markers for predicting the development of moderate or severe AKI within12 hours of sample collection. The risk for major adverse kidney events, such as death, dialysis, or persistent renal dysfunction within 30 days, was elevated sharply for [TIMP-2]•[IGFBP7] above 0.3 and doubled when values were greater than 2.0. The study was published on February 6, 2013 in the journal Critical Care.

Related Links:
Mayo Clinic
Luminex
Meso Scale Discovery