Table 3.

Suggested study designs of biomarker studies in AKI

1. Use an AKI definition that minimizes false positive misclassifications of disease status, particularly in clinical settings with relatively low expected prevalence of true AKI. Examples of appropriate AKI definitions include the following: Acute Kidney Injury Network (AKIN) stage 2 or 3, RIFLE stage “I” or “F,” or stage 2 or 3 of a definition based on SCr kinetics.6

2. Examine hard endpoints (e.g., in-hospital or 28-d mortality, need for renal replacement therapy (RRT), or substantial and sustained reduction in kidney function at 28 d) instead of short-term changes in SCr—recognizing, however, that the “injury” marker is then being tested as a prognostic marker and not necessarily an injury marker.

3. Test whether biomarkers outperform conventional measures of kidney function in the accurate identification of individuals exposed to nephrotoxic agents versus well matched, nonexposed individuals.

4. Test whether clinical outcomes (most likely intermediate endpoints such as length of stay or postoperative fluid balance, but ideally hard endpoints such as renal replacement therapy or mortality) are improved in patients who do versus do not undergo kidney injury biomarker testing with subsequent clinical decision making on the basis of biomarker results.

5. Use the approaches suggested in the biostatistical literature when a reliable gold standard does not exist20,21: for example, measurement of two biomarkers that are assumed to be conditionally independent (e.g., SCr and a novel tubular injury biomarker) in individuals drawn from two populations with different disease prevalence.