Secretory Leukocyte Protease Inhibitor (SLPI)-A Novel Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery: A Prospective Observational Study.

Averdunk Averdunk,Sobotta Sobotta,Levkovich Levkovich,Fitzner Fitzner,Moeckel Moeckel,Stoppe Stoppe,Marx Marx,Ochi Ochi,Leaf Leaf,Vieten Vieten

doi:10.3390/jcm8111931

Abstract

Acute kidney injury (AKI) is one of the most frequent complications after cardiac surgery and is associated with poor outcomes. Biomarkers of AKI are crucial for the early diagnosis of this condition. Secretory leukocyte protease inhibitor (SLPI) is an alarm anti-protease that has been implicated in the pathogenesis of AKI but has not yet been studied as a diagnostic biomarker of AKI. Using two independent cohorts (development cohort (DC), n = 60; validation cohort (VC), n = 148), we investigated the performance of SLPI as a diagnostic marker of AKI after cardiac surgery. Serum and urinary levels of SLPI were quantified by ELISA. SLPI was significantly elevated in AKI patients compared with non-AKI patients (6 h, DC: 102.1 vs. 64.9 ng/mL, p < 0.001). The area under the receiver operating characteristic curve of serum SLPI 6 h after surgery was 0.87 ((0.76–0.97); DC). The addition of SLPI to standard clinical predictors significantly improved the predictive accuracy of AKI (24 h, VC: odds ratio (OR) = 3.91 (1.44–12.13)). In a subgroup, the increase in serum SLPI was evident before AKI was diagnosed on the basis of serum creatinine or urine output (24 h, VC: OR = 4.89 (1.54–19.92)). In this study, SLPI was identified as a novel candidate biomarker for the early diagnosis of AKI after cardiac surgery.

Highlights

Acute kidney injury (AKI) is one of the most common complications after major surgery, especially after cardiac surgery [1,2]
Oliguria was detected in 21% of AKI cases in the development cohort (DC) and in 23% of AKI cases in the validation cohort (VC) (Table 1)
The overall proportion of AKI patients affected by persistent AKI (>48 h) was approximately 40% (Table 1)

Summary

Introduction

Acute kidney injury (AKI) is one of the most common complications after major surgery, especially after cardiac surgery [1,2]. Distinct consensus criteria for the early detection of AKI have been defined by the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines, AKI continues to be underdiagnosed [9]. The early identification of patients at risk could enable the timely initiation of preventive measures to reduce the sequelae of AKI [10]. In this context, the currently established and routinely used AKI indicators, such as serum creatinine and urine output, have been repeatedly demonstrated to be insufficient for the early detection of AKI because changes in serum creatinine indicative of altered kidney function are evident only after more than 50% of the baseline renal function has been compromised [11]. For a better approximation of the extent of injury and the early diagnosis, differential diagnosis, and prognosis of AKI, the international KDIGO board has called for the identification of appropriate AKI markers, analogous to serum troponin or liver enzymes used to identify organ injury [13]

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