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Urine TIMP2 × IGFBP7 increases 24 hours before severe AKI


We recently reported a 728-patient multicenter study (Sapphire) where a biomarker combination of tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) were validated for risk stratification for moderate or severe acute kidney injury (AKI) KDIGO stage 2 and 3 [1].


We subsequently selected two clinical cutoff values for the TIMP2 × IGFBP7 combination from the Sapphire dataset, one (0.3) with high sensitivity (89%) (specificity = 50%) and one (2.0) with high specificity (95%) (sensitivity = 42%) for the development of AKI KDIGO stage 2 and 3 within 12 hours of study enrolment. We examined the timing of change in TIMP2 × IGFBP7 relative to change in creatinine using the sign test.


TIMP2 × IGFBP7 results were available for 178 patients who developed AKI stage 2 or 3. The median TIMP2 × IGFBP7 result was significantly greater than the cutoff value of 0.3 from 24 hours before to 24 hours after AKI 2 or 3 (P < 0.01) (Figure 1). Conversely, median serum creatinine was not different from baseline prior to development of AKI 2 or 3.

Figure 1

NC, Nephrocheck (TIMP2 × IGFBP7); Cr, creatinine.


The TIMP2 × IGFBP7 biomarker combination identifies patients who ultimately develop moderate or severe AKI 24 hours earlier than serum creatinine.


  1. 1.

    Kashani K, et al.: Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 2013, 17: R25. 10.1186/cc12503

    PubMed Central  Article  PubMed  Google Scholar 

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Correspondence to M Ostermann.

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Ostermann, M., Chawla, L., Forni, L. et al. Urine TIMP2 × IGFBP7 increases 24 hours before severe AKI. Crit Care 18, P380 (2014).

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  • Creatinine
  • Serum Creatinine
  • Sapphire
  • Risk Stratification
  • Factor Binding