Urinary NephroCheck® test, as a marker of subclinical postoperative AKI, correlates with long-term GFR decline in patients undergoing partial nephrectomy: a prospective bicentric observational study

Abstract

Background: Nephron-sparing surgery (NSS) represents the preferred technique to treat localized renal lesions, not being exempted from the risk of postoperative acute kidney injury (AKI) to happen, though. Patients experiencing postoperative AKI, either clinical or subclinical, are more susceptible to develop chronic kidney disease.

Methods: Patients scheduled for NSS in localized renal cell carcinoma were recruited. Patients were grouped according to postoperative AKI development and postoperative NephroCheck value: group 1 (normal), no AKI and no increased biomarker; group 2 (subclinical AKI), no AKI but increased NephroCheck (> 0.3 at 4 h postoperatively); group 3, AKI and no increased NephroCheck; group 4 (clinical AKI), AKI and increased NephroCheck. Samples were collected pre- and post-operatively; renal function was re-assessed up to 24 months.

Results: Among 131 patients included, 42% developed clinical AKI. Based on NephroCheck^® and clinical AKI criteria, patients could be divided in four groups with significantly different eGFR at 24 months (p = 0.0003). Multivariate analysis confirmed clinical AKI as an independent predictor of eGFR decline at 24 months (p < 0.0003). In subclinical AKI's subgroup [20/131 (15%)], characterized by urinary NephroCheck^® >0.3 and serum creatinine increase < 0.3 mg/dL, NephroCheck^® appeared as an independent predictor of severe eGFR decline at 24 months (OR 3.76, p = 0.02); in this subgroup, eGFR decline resulted significantly more severe compared to eGFR decline in patients with neither serum creatinine nor tubular damage markers' elevation.

Conclusions: In patients undergoing NSS, the most reliable predictor of long-term eGFR decline is represented by the occurrence of postoperative clinical AKI. In this setting, NephroCheck^® appeared able to identify 'subclinical AKI' and consequently patients at increased risk of 24-month-eGFR decline.

Keywords: Acute kidney injury; IGFBP7; NephroCheck; Partial nephrectomy; Renal cell carcinoma; TIMP-2.

Fig. 1

Trends in estimated glomerular filtration rate (eGFR) decline in patients with and without a severe eGFR decline at 24 months postoperatively. Boxplot show eGFR trends in patients with (≥ 8.3 mL/min) and without a severe eGFR decline at 24 months postoperatively. In the group with a severe eGFR decline, eGFR resulted statistically different at 24 h postoperatively, and 18 and 24 months (p < 0.05). Asterisks indicate a significant difference among groups (p < 0.05)

Fig. 2

Trends in estimated glomerular filtration rate (eGFR) decline in four groups defined by eGFR and NephroCheck^® test. Line graph show eGFR trends in four groups of patients, defined by eGFR and NephroCheck^® test. In the different groups eGFR resulted statistically different at 24 h postoperatively, and 12, 18 and 24 months (p < 0.05). Group one (no clinical AKI, NephroCheck^® ≤0.3) and group two (no clinical AKI, NephroCheck^® >0.3) present almost identical pre-operative characteristics, but postoperative NephroCheck^® test. Asterisks indicate a significant difference among groups (p < 0.05)

Fig. 3

Flow chart illustrating the selection criteria for the study population. This flow diagram illustrates inclusion and exclusion criteria for patient selection from the two Centers. Measurement of the NephroCheck^® values complements the information obtained by measurement of sCr levels in establishing the diagnosis of clinical/subclinical AKI and predicting patients’ renal prognosis