Serum Cystatin C Is an Early Predictive Biomarker of Acute Kidney Injury after Pediatric Cardiopulmonary Bypass

The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 09/2010; 5(9):1552-7. DOI: 10.2215/CJN.02040310
Source: PubMed


Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). Serum creatinine (SCr), the current standard, is an inadequate marker for AKI since a delay occurs before SCr rises. Biomarkers that are sensitive and rapidly measurable could allow early intervention and improve patient outcomes. We investigated the value of serum cystatin C as an early biomarker for AKI after pediatric CPB.
We analyzed data from 374 prospectively enrolled children undergoing CPB. Serum samples were obtained before and at 2, 12, and 24 hours after CPB. Cystatin C was quantified by nephelometry. The primary outcome was AKI, defined as a > or =50% increase in SCr. Secondary outcomes included severity and duration of AKI, hospital length of stay, and mortality. A multivariable stepwise logistic regression analysis was used to assess predictors of AKI.
One hundred nineteen patients (32%) developed AKI using SCr criteria. Serum cystatin C concentrations were significantly increased in AKI patients at 12 hours after CPB (P < 0.0001) and remained elevated at 24 hours (P < 0.0001). Maximal sensitivity and specificity for prediction of AKI occurred at a 12-hour cystatin C cut-off of 1.16 mg/L. The 12-hour cystatin C strongly correlated with severity and duration of AKI as well as length of hospital stay. In multivariable analysis, 12-hour cystatin C remained a powerful independent predictor of AKI.
Serum cystatin C is an early predictive biomarker for AKI and its clinical outcomes after pediatric CPB.

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    • "Improving our ability to diagnose AKI, maybe with the concomitant use of multiple markers, will allow the implementation of more effective preventive and therapeutic measures to improve AKI prognosis. Finally, some studies have included newborns and older children when evaluating AKI biomarkers [57]. This can lead to erroneous interpretations, as cutoff values can be different even in those patients with different gestational ages and birth weights. "
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    ABSTRACT: In the past 10 years, great effort has been made to define and classify a common syndrome previously known as acute renal failure and now renamed "acute kidney injury (AKI)." Initially suggested and validated in adult populations, AKI classification was adapted to the pediatric population and recently has been modified for the neonatal population. Several studies have been performed in adults and older children using this consensus definition, leading to improvement in the knowledge of AKI incidence and epidemiology. In spite of these advances, the peculiar renal pathophysiology of critically ill newborn patients makes it difficult to interpret urine output (UO) and serum creatinine (SCr) levels in these patients to diagnose AKI. Also, new urine biomarkers have emerged as a possible alternative to diagnose early AKI in the neonatal population. In this review, we describe recent advances in neonatal AKI epidemiology, discuss difficulties in diagnosing AKI in newborns, and show recent advances in new AKI biomarkers and possible long-term consequences after AKI episode.
    03/2014; 2014(4):601568. DOI:10.1155/2014/601568
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    • "For Cystatin C, we used a median above 1.16 mg/L as suggested by Catherine D.Krawczeski.15 Cystatin C changes obeyed the X2 pattern during the study period (p value = 0.01). "
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    ABSTRACT: Acute kidney injury (AKI) is a common and life-threatening complication following coronary artery bypass graft (CABG). Neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C have shown to be good predictive factors for AKI. Recently, there has been a growing interest in the use of hypertonic saline in cardiac operations. The purpose of this study was to evaluate the prophylactic anti-inflammatory effect of hypertonic saline (Group A) infusion versus normal saline (Group B) on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients. This randomized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center, Tehran, Iran. After applying exclusion criteria, the effects of preoperative hypertonic saline (294 meq Na) versus normal saline (154 meq Na) infusion on serum NGAL and Cystatin C levels were investigated in three intervals: before surgery and 24 and 48 hours postoperatively. The probable intraoperative or postoperative confounders, including pump time, cross-clamp time, heart rate, systolic and diastolic blood pressures, central venous pressure, arterial pH, partial pressure of arterial oxygen, fraction of inspired oxygen, blood sugar, Na, K, Mg, hemoglobins, white blood cells, hematocrits, and platelets, were recorded and compared between the two groups of study. The study population comprised 40 patients, including 25 (62.5%) males, at a, mean age ± SD of 61.75 ± 8.13 years. There were no statistically significant differences between the patients' basic, intraoperative, and postoperative characteristics, including intraoperative and postoperative hemodynamic variables and supports such as inotropic use. Intra-aortic balloon pump use and mortality were not seen in our cases. Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml. Moreover, 10 patients in Group A and 17 patients in group B showed a rise in serum Cystatin C levels above 1.16 mg/dl. Patients with AKI had significantly elevated NGAL and Cystatin C levels (p value < 0.001), but there were no significant differences in the decrease in the NGAL level in the hypertonic saline group versus the normal saline group (230.91 ± 92.68 vs. 239.74 ± 116.58 ng/ml, respectively; p value = 0.792), or in the decrease in the Cystatin C level in the hypertonic saline group versus the normal saline group (1.05 ± 0.26 vs. 1.06 ± 0.31, respectively; p value = 0.874). Pre-treatment of CABG patients with hypertonic saline had no significant effect on serum NGAL and Cystatin C levels compared to the normal saline-receiving group. Our present data, albeit promising, have yet to fully document outcome differences.
    01/2013; 8(1):21-7.
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    • "In the 44 patients who developed AKI, the increase of cystatin C (>50% over baseline) preceded that of creatinine by 1.5 days. A more recent study has shown cystatin C to rise significantly at 12 hr after pediatric cardiopulmonary bypass in patients who subsequently developed AKI [82]. Compared to NGAL, cystatin C rises later in AKI, with several studies in adults administered contrast showing an early rise in both urine (4 hr) and plasma (2 hr) NGAL compared to a later increase in cystatin C (8-24 hr) [83-85]. "
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    ABSTRACT: Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionize the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage.
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