New predictors for acute kidney injury in critically ill
By Sally Robertson, medwireNews Reporter
04 March 2013
Crit Care 2013; Advance online publication

medwireNews: Researchers have identified two novel markers for acute kidney injury (AKI) that could improve physicians' ability to identify risk for AKI among critically ill patients.

Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) performed better than any other biomarker reported to date, in a two-stage study of over 1000 patients, report John Kellum (University of Pittsburgh, Pennsylvania, USA) and colleagues.

Acute kidney injury (AKI) can evolve quickly because it is difficult to identify before loss of organ function, when interventions may provide benefit, explains the team. However, identifying early markers of kidney damage has proved difficult as the disease has many different etiologies and the cause in any given patient is often likely to be multifactorial.

In a two-phase study, Kallum and team analyzed 340 potential biomarkers, including previously described ones as well as new candidates, in a cohort of 522 patients admitted to an intensive care unit who had at least one risk factor for AKI. They then validated the performance of the two strongest biomarkers identified (TIMP-2 and IGFBP7) in a cohort of 728 critically ill patients (with respiratory or cardiovascular dysfunction) without evidence of AKI.

"Because we felt the most important unanswered question was early risk stratification, we chose to study patients without evidence of AKI and sought to predict its clinical manifestation over the next 12 hours," explains the team.

As reported in Critical Care, 101 (14%) individuals in the validation cohort developed moderate or severe AKI (corresponding to KDIGO [Kidney Disease: Improving Global Outcomes] stage 2 and 3) within 12 hours, 218 (30%) developed it within 7 days, and 49 (67%) underwent renal replacement therapy during their hospital stay (truncated at 30 days).

"We chose to assess risk for moderate to severe AKI rather than all AKI because this severity… has been shown to be associated with a significantly increased incidence of clinically important outcomes such as need for renal replacement therapy, in hospital death, and persistent renal dysfunction," write Kallum and team.

Receiver-operating characteristic analysis showed that the area under the curve (AUC) for the development of AKI within 12 hours was 0.76 and 0.79 for IGFBP7 and TIMP-2, respectively. When combined, the markers demonstrated an AUC of 0.80.

The combination of TIMP2 and IGFBP7 significantly outperformed all previously described markers for AKI, none of which achieved an AUC of more than 0.72, report the researchers.

Furthermore, TIMP-2 and IGFBP7 combined significantly improved risk stratification when a clinical model with nine variables was analyzed using Cox proportional hazard modeling, generalized estimating equation, integrated discrimination improvement, or net reclassification improvement.

"We believe that these markers are the most promising early markers of AKI reported to date," concludes the team.

medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

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