Elevated Soluble Urokinase Plasminogen Activator Receptor and Proenkephalin Serum Levels Predict the Development of Acute Kidney Injury after Cardiac Surgery

Abstract

Acute kidney injury (AKI) develops in up to 40% of patients after cardiac surgery. The soluble urokinase plasminogen activator receptor (suPAR) has been identified as a biomarker for incident chronic kidney disease (CKD). Proenkephalin (proENK) also has been shown to be a biomarker for renal dysfunction. We hypothesized that pre-surgery suPAR and proENK levels might predict AKI in patients undergoing cardiac surgery. Consecutive patients (n = 107) undergoing elective cardiac surgery were studied prospectively. Clinical data, laboratory parameters, suPAR and proENK serum levels were assessed before operation, after operation and days one and four post-operatively. A total of 21 (19.6%) patients developed AKI within the first four days after elective surgery. Serum levels of suPAR and proENK, but not of creatinine, were significantly higher before surgery in these patients compared to those patients without AKI. This difference remained significant for suPAR, if patients with or without AKI were matched for risk factors (hypertension, diabetes, CKD). If cardiac surgery patients with pre-existing CKD (n = 10) were excluded, only pre-operative suPAR but not proENK serum levels remained significantly elevated in patients with subsequent AKI. Thus, our findings indicate that suPAR may be a predictive biomarker for AKI in the context of cardiac surgery, even in patients without underlying CKD.

Keywords: acute kidney failure; acute kidney injury; biomarker; cardiac surgery; pro-ENK; proenkephalin; soluble urokinase plasminogen activator receptor; suPAR.

Figure 1

Serum concentrations of different biomarkers for AKI before surgery. (A) Serum suPAR levels were determined by enzyme linked immunoassay (ELISA) and revealed significantly higher levels at baseline for patients developing AKI within four days after surgery than patients without AKI. (B) Serum proENK levels were significantly elevated in patients with AKI after surgery. (C) In contrast, serum creatinine levels were not different between the two groups. (D–F) Serum levels of suPAR, proENK and creatinine of patients before cardiac surgery, excluding patients with the diagnosis of chronic kidney disease (CKD) such as diabetic nephropathy. (G–I) Serum levels of suPAR, proENK and creatinine immediately after cardiac surgery, excluding patients with chronic kidney disease. Box plot are displayed, where the bold line indicates the median per group, the box represents 50% of the values. The horizontal lines show minimum and maximum values of calculated non-outlier values; asterisks and open circles indicate outlier values (* p < 0.05, ** p < 0.01).

Figure 1

Serum concentrations of different biomarkers for AKI before surgery. (A) Serum suPAR levels were determined by enzyme linked immunoassay (ELISA) and revealed significantly higher levels at baseline for patients developing AKI within four days after surgery than patients without AKI. (B) Serum proENK levels were significantly elevated in patients with AKI after surgery. (C) In contrast, serum creatinine levels were not different between the two groups. (D–F) Serum levels of suPAR, proENK and creatinine of patients before cardiac surgery, excluding patients with the diagnosis of chronic kidney disease (CKD) such as diabetic nephropathy. (G–I) Serum levels of suPAR, proENK and creatinine immediately after cardiac surgery, excluding patients with chronic kidney disease. Box plot are displayed, where the bold line indicates the median per group, the box represents 50% of the values. The horizontal lines show minimum and maximum values of calculated non-outlier values; asterisks and open circles indicate outlier values (* p < 0.05, ** p < 0.01).

Figure 2

Predictive value of AKI biomarkers and longitudinal assessment. (A) and (B) receiver operating characteristic (ROC) curve analyses for pre-operative suPAR, proENK and creatinine to predict post-surgery AKI for all patients (A) and patients without prior CKD (B). (C) suPAR and proENK serum levels over time (pre- and post-operation, day 1 and day 4 after operation) for patients without prior CKD. (D) SuPAR and creatinine serum levels over time in patients developing AKI compared to patients without AKI development. AUC: Area under the curve.