Characterising acute kidney injury: The complementary roles of biomarkers of renal stress and renal function

• Published in: Journal of critical care 2022-10, Vol.71, p.154066-154066, Article 154066
• Main Authors: Forni, Lui G., Joannidis, Michael, Artigas, Antonio, Bell, Max, Hoste, Eric, Joannes-Boyau, Olivier, Kashani, Kianoush, Koyner, Jay, Rimmele, Thomas, Shi, Jing, Ostermann, Marlies, Chawla, Lakhmir S., Kellum, John A.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury; Biomarkers; Confidence intervals; Creatinine; Critical care; Humans; Insulin-Like Growth Factor Binding Proteins; Kidney - physiology; Kidneys; Medicin och hälsovetenskap; Pathophysiology; Plasma; Predictive Value of Tests; Prospective Studies; Tissue Inhibitor of Metalloproteinase-2; Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119–159 (PENK); Urine
• ISSN: 0883-9441; 1557-8615; 1557-8615
• DOI: 10.1016/j.jcrc.2022.154066

Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119–159 2 were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2–3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76–0.84) to 0.85 (0.81–0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone. •We have examined biomarkers of AKI associated with renal stress from the Sapphire study together with PENK a relatively new marker of glomerular filtration.•We demonstrate that a combination of stress biomarkers plus creatinine improves risk stratification but markers such as cystatin C or PENK do not.•Of note the biomarkers associated with stress are not elevated in CKD whereas the others, unsurprisingly, are.