#2508 Urinary [TIMP-2]*[IGFBP7] as the ultimate potential biomarker of subclinical Acute Kidney Injury after kidney surgery: a multicentric study
Authors: Allinovi Marco , Casiraghi Micaela Anna , Tofani Lorenzo , Villa Gianluca 
Published: May 2024

Abstract

Background and Aims
Nephron-sparing surgery (NSS) represents the preferred technique to treat localized renal lesions and better preserve kidney function. Still it is not exempted from the risk of postoperative acute kidney injury (AKI) to happen, with a reported incidence ranging from 5.5% to 34%.
Patients experiencing postoperative AKI, either clinical or subclinical, are more susceptible to chronic kidney disease (CKD). The latter represents a difficult-to-identify subpopulation characterized by tubular damage biomarker's rising without changes in serum creatinine (scr), that after surgery is less likely to be included among the ones deserving a closer follow-up, but actually needing one, as this subpopulation's long term outcomes slightly differ from individuals recovered from clinical postoperative AKI.
This is the reason why a standardized tool for early identification of patients suffering from subclinical AKI is required, to allow a customized postoperative surveillance, promote strategies of nephroprotection and reduce the incidence of CKD and end-stage kidney disease.
Recent evidences show that by exclusively following outdated consensus criteria for AKI (changes in scr, urine output), 15-20% of patients undergoing through acute tubular injury and suffering from its adverse outcomes are likely to be missed. Only recently, FDA approved NephroCheck® biomarker, which combines two urinary markers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7). It represents the first effective test for AKI's risk assessment.
In a previous monocentric study [1], our group presented NephroCheck® as a biomarker able to efficiently identify subclinical AKI and predict long-term eGFR decline after robotic NSS. In order to confirm our previous results, we recruited a larger cohort and performed a multicentric study.

Method
We prospectively observed all patients scheduled for robotic NSS in suspected localized renal cell carcinoma in two different Centers from 2016 to 2018.
Samples were collected preoperatively and postoperatively (4 h, 10 h, 24 h, 48 h), while kidney function was re-assessed up to 24 months.
A multivariate logistic analysis was performed to evaluate the association between different parameters and eGFR decline at 24 months.

Results
A total number of 131 patients were included; 55/131 (42%) developed clinical AKI. A significant association between NephroCheck® at 4 h and clinical AKI, as stated by KDIGO Guidelines, is confirmed (p = 0.0055).
In the overall cohort, the multivariate analysis shows that only clinical AKI appears as an independent factor for predicting eGFR decline at 24 months (p &lt; 0.0003), while postoperative NephroCheck® alone did not (p = 0.92).
Based on NephroCheck® measured 4 h after surgery and clinical AKI, patients can be divided in four groups with significantly different eGFR at 24 months (p = 0.0003) (Fig. 1).
Not considering patients who experienced clinical AKI, the independent role of different parameters in predicting severe eGFR decline at 24 months was evaluated by multivariate logistic analysis; in this subgroup of patients, NephroCheck® evaluated at 4 h postoperatively appears as an independent factor able to predict a severe eGFR decline at 24 months (OR 3.76, p = 0.02) (Fig. 2).

Conclusion
NephroCheck®, in combination with scr, represents an accurate and easy-to-use test, likely able to early identify long-term eGFR decline in patients undergoing NSS surgery that don't develop a clinically evident postoperative AKI (subclinical AKI), making it possible to identify those in need of closer-up surveillance, reducing the incidence and progression of CKD.
Still, clinical postoperative AKI is confirmed as the most important prognostic parameter and predictive factor for eGFR decline in the long-term.
Further studies are needed, particularly focusing on application of NephroCheck® in setting other than NSS.