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. 2023 Mar 28;11(4):1046.
doi: 10.3390/biomedicines11041046.

Novel Biomarkers for Early Detection of Acute Kidney Injury and Prediction of Long-Term Kidney Function Decline after Partial Nephrectomy

Marco Allinovi  1 , Francesco Sessa  2 , Gianluca Villa  3   4 , Andrea Cocci  2 , Samantha Innocenti  1 , Maria Zanazzi  1 , Lorenzo Tofani  4 , Laura Paparella  3 , Dritan Curi  1 , Calogero Lino Cirami  1 , Riccardo Campi  2 , Andrea Mari  2 , Agostino Ognibene  5 , Maria Lorubbio  5 , Alessandra Fanelli  5 , Stefano Romagnoli  3   4 , Paola Romagnani  6   7 , Andrea Minervini  2   8
Affiliations

Novel Biomarkers for Early Detection of Acute Kidney Injury and Prediction of Long-Term Kidney Function Decline after Partial Nephrectomy

Marco Allinovi et al. Biomedicines. .

Abstract

Background: Identifying acute kidney injury (AKI) within few hours of onset is certainly helpful. However, early prediction of a long-term eGFR decline may be an even more important goal. Our aim was to identify and compare serum [creatinine, kineticGFR, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL)] and urinary (NephroCheck, NGAL, proteinuria, albuminuria, acantocytes at urinary sediment) predictors of AKI that might efficiently predict long-term GFR decline after robotic Nephron-Spearing Surgery (rNSS).

Methods: Monocentric prospective observational study. Patients scheduled for rNSS for suspected localized Renal Cell Carcinoma from May 2017 to October 2017 were enrolled. Samples were collected preoperatively and postoperatively (timepoints: 4 h, 10 h, 24 h, 48 h), while kidney function was re-assessed up to 24 months.

Results: 38 patients were included; 16 (42%) developed clinical AKI. The eGFR decline at 24 months was more pronounced after postoperative AKI (-20.75 vs. -7.20, p < 0.0001). KineticGFR at 4 h (p = 0.008) and NephroCheck at 10 h (p = 0.001) were, at multivariable linear regression analysis, efficient predictors of post-operative AKI and long-term eGFR decline if compared to creatinine (R2 0.33 vs. 0.04).

Conclusions: NephroCheck and kineticGFR have emerged as promising noninvasive, accurate, and early biomarkers of postoperative AKI and long-term GFR decline after rNSS. Combining NephroCheck and kineticGFR in clinical practice would allow to identify high risk of postoperative AKI and long-term GFR decline as early as 10 h after surgery.

Keywords: IGFBP7; NGAL; NephroCheck; TIMP-2; acute kidney injury; biomarkers; partial nephrectomy; renal cell carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of different biomarkers of AKI which were selected and tested in our study in relation of sites of injury in the nephron. NGAL, neutrophil gelatinase-associated lipocalin; IGFBP7, insulin-like growth factor binding protein 7; TIMP2, tissue inhibitor of metalloproteinase-2.
Figure 2
Figure 2
The postoperative change in biomarker levels from baseline to 24 h after surgery. Different graphs summarize the pattern of post-operative changes of the studied biomarkers as well as serum creatinine, both in patients who experienced AKI (red) and non-AKI (blue) Asterisk indicates p < 0.05. AKI; Acute Kidney Injury. Serum creatinine is expressed in mg/dL, serum cystatin C in mg/L, serum and urinary NGAL (neutrophil gelatinase-associated lipocalin) in ng/mL, kinetic GFR (glomerular filtration ratio) in mL/min/1.73 m2, NephrocheckTM is the ratio between TIMP-2 (tissue inhibitor of metalloproteinase-2) in ng/mL and IGFBP7 (insulin-like growth factor binding protein 7) in ng/mL and it is expressed as an AKIRISKTM Score (≤0.3 low-risk of AKI, >0.3 high-risk of AKI), albuminuria is expressed in mg/g, proteinuria is expressed in mg/dL.
Figure 3
Figure 3
Estimated glomerular filtration rate (eGFR) decline at 6, 12, 18 and 24 months after surgery. * The median eGFR decline at 18 and 24 months after surgery was significantly faster in patients who experienced postoperative AKI. AKI; Acute Kidney Injury. eGFR in mL/min/1.73 m2, estimated using CKD-EPI formula.
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