Supplementary Material for: Serum IGFBP7 deriving from spleen and lung could be used for early recognition of cardiac surgery-associated acute kidney injury

Introduction: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. Methods: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischaemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery, and at inclusion (0 h), 2 h, 6 h and 12 h after Intensive Care Unit (ICU) admission, and compared with serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR) and serum uric acid (UA). Results: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (s[IGFBP7]-2 h) was significantly higher in patients who developed AKI. The relationships between s[IGFBP7]-2 h in AKI patients and log2(SCr), log2(BUN), log2(eGFR), and log2(UA) were statistically significant. The diagnostic performance of s[IGFBP7]-2 h measured by the macro-averaged area under the receiver operating characteristic curve (AUC) was 0.948 ([95% CI], 0.853 to 1.000; P<0.001). Discussion/Conclusion: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.