The presence of 2 urinary biomarkers may refine the Kidney Disease Improving Global Outcomes (KDIGO) grading system of acute kidney injury (AKI).

At any given AKI stage, the product of tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulinlike growth factor binding protein 7 (IGFBP7) identified patients at increased risk for death, investigators reported in JAMA Network Open. These cell-cycle arrest biomarkers are produced by kidney tubule epithelial cells in response to kidney stress. A [TIMP-2] × [IGFBP7] score higher than the threshold of 2.0 (ng/mL)2/1000 defined patients who are biomarker positive.

Among 999 critically ill patients with septic shock from the Protocolized Care for Early Septic Shock (ProCESS) trial, 15.2%, 29.4%, and 18% had KDIGO AKI stage 1, 2, and 3, respectively, within 24 hours of trial enrollment. Investigators calculated the [TIMP-2] × [IGFBP7] product for each patient at 6 hours after enrollment. Of the cohort, 196 (19.6%) were biomarker positive.

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Within 30 days, 193 patients (19.3%) died. Biomarker-positive vs biomarker-negative patients with KDIGO AKI stage 1, 2, and 3 had 2.2-, 1.5-, and 1.6-fold higher risk for mortality within 30 days, respectively, John A. Kellum, MD, of the University of Pittsburgh in Pennsylvania, and colleagues reported. The biomarker score was not prognostic in patients without AKI.

The 23rd Acute Disease Quality Initiative (ADQI-23) consensus conference proposed integrating biomarkers into AKI staging.

“Our results suggest that in patients with septic shock who have developed AKI according to KDIGO staging, the addition of urinary [TIMP-2] × [IGFBP7] level may identify patients at any functional AKI stage who may have lower 30-day survival,” Dr Kellum’s team concluded. “Additional [TIMP-2] × [IGFBP7] cutoff levels explored in this study may deserve further investigation for the ability to stratify patients even in the absence of functional criteria for AKI.”


Molinari L, Del Rio-Pertuz G, Smith A, et al. Utility of biomarkers for sepsis-associated acute kidney injury staging. JAMA Netw Open. Published online May 18, 2022. doi:10.1001/jamanetworkopen.2022.12709