In search of the holy grail of biomarkers

This week at BMC Nephrology, an article by Tao et al. discusses whether specific renal biomarkers are able to predict the progression of acute renal failure (AKI) in septic patients. In our upcoming BMC Nephrology blog, blog editor Dr. Daphne Knicely examines the use of biomarkers in ARI.

Up to 50% of intensive care unit stays are complicated by acute kidney disease (AKI). This is associated with a longer hospital stay, more hospital deaths, higher healthcare costs and a risk of developing chronic kidney disease (CKD) and / or a progression of IRC.

Biomarkers have recently become of interest for their potential role in the prevention of ARI in high risk patients, the early diagnosis of ARI, the identification of different kidney diseases and the progression of ARI and disease. underlying renal. Biomarkers are various substances that can be found in blood or urine that could suggest injury or disease, and in our context kidney damage. There is hope that these biomarkers will provide a reliable, non-invasive way to test and guide the management of ARI.

In a study published in BMC Nephrology this week, Tao et al. studied the potential of a few biomarkers independently and in combination as predictors of the progression of ARI induced by sepsis. The group studied the product of urinary tissue metalloproteinase-2 inhibitor (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7) (u[TIMP-2]*[IGFBP7]), molecular urinary renal failure-1 (uKIM-1) and urinary interleukin-18 (uIL-18).

TIMP-2 and IGFBP7 are released in the urine in response to stress from renal epithelial cells and mediate cell cycle arrest in tubular epithelial cells. Each of these markers has been shown to predict ARI associated with cardiac surgery, but the product of these urinary biomarker levels has been found to be more informative (see Table). KIM-1 and IL-18 suggest renal tubular damage and inflammation associated with ARI. These biomarkers have been shown in other studies to reflect the prediction of the progression of ARI.

Cummings et al. you[TIMP-2]*[IGFBP7] was able to predict moderate to severe ARI postoperatively
Maizel et al. you[TIMP-2]*[IGFBP7] in the early phase of septic shock was an independent risk factor to identify the population at high risk for progression of mild and moderate to severe ARI over the next 24 hours

Current research suggests that the value may not be with a single marker but in combinations of these markers.

In this study, Tao et al. demonstrated that all of these markers independently predicted sepsis-induced ARI progression, but u[TIMP-2]*[IGFBP7] showed the best prediction. They noted that a combination of u[TIMP2]*[IGFBP7] with uKIM-1 improved performance in predicting sepsis-induced ARI progression.

Hundreds of other biomarkers are being explored for the early and high-risk detection of ARI. Current research suggests that the value may not be with a single marker but in combinations of these markers. The introduction of markers as clinical tools can have several advantages, such as:

  • Early identification of patients at high risk of ARI;
  • Early implementation of renal protective measures such as KDIGO bundles (i.e. AKI care bundles) and avoidance of nephrotoxins;
  • Avoid complications from ARI and the need for kidney replacement therapy

Currently, biomarkers are expensive, not readily available, and some are too specific or too sensitive. Could the use of a biomarker be helpful or lead to more unnecessary testing and treatment leading to increased healthcare costs? More research needs to be done before these markers can be used in clinical settings as potential tools to determine the prognosis and guide the clinical management of patients with acute renal failure.

If these biomarkers were made available to you as a clinical tool, would you use them?

Amanda J. Marsh