Elsevier

Clinical Biochemistry

Volume 46, Issues 13–14, September 2013, Pages 1244-1251
Clinical Biochemistry

Biomarkers of acute kidney injury in pediatric cardiac surgery

https://doi.org/10.1016/j.clinbiochem.2013.07.008Get rights and content

Highlights

  • The evaluation of serume and urinary biomarkers to predict AKI after CPB.

  • AKI occures in 16.1% of children who underwent CPB.

  • Perfect AKI predictor at 2 hours after surgery is uL-FABP.

  • At 6 and 24 hours after surgery perfect predictor is uNGAL.

Abstract

Objectives

Acute kidney injury (AKI) is a significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB.

Design and methods

We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48 h postoperatively in children undergoing CPB during cardiac surgery. AKI was defined as ≥ 25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48 h after surgery.

Results

Of the 112 patients, 18 patients (16.1%) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In the AKI compared to the non-AKI group, sCysC at 2 h, and uNGAL and uL-FABP at 2–48 h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2 h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24 h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively).

Conclusions

sCysC, uNGAL and uL-FABP are reliable early predictors for AKI after CPB. By allowing earlier timing of injury and earlier intervention, they could improve AKI outcome.

Introduction

Acute kidney injury (AKI) is a significant problem in children undergoing cardiac surgery. Approximately 30–50% of these patients suffer from varying degrees of AKI after cardiopulmonary bypass (CPB) [1], [2], [3]. AKI is known to increase the duration of mechanical ventilation and prolong intensive care and hospital stays [2]. It carries a mortality rate as high as 20–79% in children requiring dialysis [4]. Even a minor degree of postoperative AKI, as manifested by only a 0.2–0.3 mg/dL rise in serum creatinine (sCr) from baseline levels, predicts a significant increase in mortality and morbidity [5], [6]. AKI survivors are also at risk for progression to CKD [7], [8], [9].

Defining AKI according to sCr and urine output is not ideal. In fact, sCr measures function, not injury. It may not change until approximately 50% of kidney function has been lost. In addition, sCr level is affected by multiple confounding factors such as age, gender, diet, muscle mass, race, and hydration status. In the early neonatal period, it is a reflection of the mother's renal function more than the infant's. Additionally, sCr levels are influenced by tubular creatinine secretion, by certain drugs and by the Jaffe method for its measurement, especially in neonates with increased serum bilirubin levels. Urine output, another classic diagnostic AKI marker has limited sensitivity [10].

Animal studies have shown that AKI treatments need to be administered soon after injury to be effective [11], [12], [13]. The importance of developing and defining new biomarkers of kidney diseases that can be used for early diagnosis, assessment of severity, and long term prognosis has been emphasized by the American Society of Nephrology and the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK). Cardiac biomarkers such as troponins have been shown to be superior to clinical assessment in the diagnosis of myocardial infarction or decompensated heart failure [14]. It is expected, that renal biomarkers will similarly improve the diagnosis of imminent AKI. Early diagnosis of AKI could facilitate early initiation of supportive measures and facilitate trials of novel therapeutic strategies [15], [16].

Many promising candidates as biomarkers for the early diagnosis of AKI, including neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), interleukin-6 and -18 (IL-6 and IL-18, respectively), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), beta-2 microglobulin (β-2M) and osteopontin, have been recently tested [11], [12], [13], [15], [16], [17], [18]. However, there is heterogeneity in the reported predictive ability of AKI biomarkers. This is in part related to the use of different AKI definitions [19], different types of biomarkers [20], [21], different times of their measurements after CPB [15], or condition of sample storage [22]. Children after cardiac surgery are an ideal type of patient with whom studying of AKI biomarkers is possible without the influence of comorbidities that complicate similar studies in adults, such as diabetes, chronic hypertension, atherosclerosis, and nephrotoxin use.

The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine KIM-1(uKIM-1), and urine L-FABP (uL-FABP) to predict AKI presence and severity in children undergoing CPB.

Section snippets

Patients and study design

We performed a prospective study of consecutive children undergoing cardiac surgery using CPB in a single center from March 1st to December 31st, 2011. All patients underwent the CPB by the same team of surgeons in a uniform pre- and postoperative setting despite all having differences in terms of diagnosis. Exclusion criteria included age above 18 years, preexisting AKI or chronic kidney disease (CKD) (e.g.: those with estimated creatinine clearance below age adjusted normal), congenital

Results

One hundred and twenty patients were eligible and 112 of them were enrolled in the study as 8 patients did not have pre-op sCr. There were 65 boys and 47 girls of median age 1.6 (IQR: 0.4–4.7) years. The total number of neonates was 20 (16.8%); of these 14 (70%) were in the non-AKI group. There were 28 infants (25.0%).

The primary outcome, AKI, defined as ≥ 25% decrease in eCCl from baseline values at 48 h postoperatively developed in 18 patients (16.1%). Transient decrease of eCCl (96% within the

Discussion

The association between CPB and AKI is well recognized [28]. However, its complex pathophysiology is not completely understood [11]. In addition, despite encouraging results on AKI treatment in animal studies [13], no specific treatment has yet been successful in humans, primarily due to the lack of the early accurate diagnostic markers. Many new biomarkers offer promise for early AKI diagnosis [13]. Based on the multifactorial etiology of AKI after CPB, it is likely that a panel of biomarkers

Conclusion

Younger age and longer CPB predisposed to AKI, which occurs in 16.1% of children who underwent CPB. Serum cystatin C, and urine NGAL and L-FABP were reliable early predictors for AKI after CPB. They correlated with disease severity and clinical outcome. The perfect AKI predictor at 2 h after surgery is urinary L-FABP, while at 6 and 24 h after surgery, the perfect AKI predictor is uNGAL. There seems to be no convincing evidence that, in addition to uNGAL, or L-FABP, the performance of sNGAL and

Conflict of interest

None.

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    Financial support: This work was financially supported by a grant from the Ministry of Education, Science and Technological Development Republic of Serbia (Project Numbers 175035 and 175079).

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