Associations of Perioperative Renal Oximetry Via Near-Infrared Spectroscopy, Urinary Biomarkers, and Postoperative Acute Kidney Injury in Infants After Congenital Heart Surgery: Should Creatinine Continue to Be the Gold Standard?

Abstract

Objective: Examine the relationship between perioperative renal regional oximetry (rSO2), urinary biomarkers, and acute kidney injury (AKI) in infants after congenital cardiac surgery with cardiopulmonary bypass. Design: Prospective, observational. Setting: Cardiac operating room and intensive care unit (CICU) Patients: Neonates and infants without history of kidney injury or anatomic renal abnormality. Interventions: None. Measurements and Main Results: Renal rSO2 was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinases 2 (TIMP-2) together with insulin-like growth factor-binding protein 7 (IGFBP7) were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no AKI, Stage 1, or Stage 2–3 AKI using KDIGO criteria with 43/70 (61%) meeting criteria for any stage AKI. Stage 2–3 AKI patients had higher [TIMP-2]•[IGFBP7] at 2 hours (0.3 vs. 0.14 for Stage 1 AKI and 0.05 for no AKI, P=0.052) and 24 hours postop (1.71 vs. 0.27 for Stage 1 AKI and 0.19 for no AKI, P=0.027) and higher NGAL levels at 24 hours postop (10.3 vs. 3.4 for Stage 1 AKI and 6.2 for no AKI, P=0.019). Stage 2–3 AKI patients had lower mean CICU renal rSO2 (66% vs. 79% for Stage 1 AKI and 84% for no AKI, P=0.038). Regression analyses showed that [TIMP-2]•[IGFBP7] at 2 hours postop and nadir intraoperative renal rSO2 to be independent predictors of postoperative kidney damage as measured by urinary NGAL. Conclusions: We observed modest differences in perioperative renal rSO2 and urinary biomarker levels compared between AKI groups classified by creatinine-dependent KDIGO criteria, but there were significant correlations between renal rSO2, [TIMP-2]•[IGFBP7], and postoperative NGAL levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone and continuous monitoring of renal rSO2 may be more sensitive to important subclinical AKI.

Neutrophil gelatinase-associated lipocalin as an early indicator of acute kidney injury following pediatric cardiac surgery

“…Studies have shown a correlation between low intraoperative perirenal rSO 2 values and the development of postoperative AKI following pediatric cardiac surgery 21,22) . In this study, although the derived val- Data are presented as median (interquartile range) .…”

Patterns of Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury in Neonates Receiving Cardiopulmonary Bypass

“…Prior to this study, research investigating the relationship between uNGAL and AKI in neonates undergoing cardiac repair using CPB has been limited. In contrast, a robust pediatric literature, examining more than 2200 children, describes uNGAL's association with and ability to predict AKI in older children [11,13,18,19,24,[27][28][29][30][31][32]. In general, these studies demonstrate an abrupt early rise in uNGAL post-operatively from low preoperative baseline values in those children who develop AKI.…”

“…In the TRIBE consortium, for example, the strength of the association between elevated uNGAL and AKI was diminished in patients <2 years of age [29]. Among infants <1 year of age, both Adams et al and Ruff et al demonstrated no difference in post-CPB uNGAL values between those with and without AKI [27,28]. In a smaller subgroup of neonates undergoing CPB, Krawczeski et al also noted post-CPB rises from baseline in uNGAL regardless of AKI status in the 35 neonates studied; however, in the eight neonates who developed AKI, the early uNGAL rise was steep enough to provide discrimination between AKI and no-AKI at 2 h post-CPB [19].…”

“…Further limitations of this study are that this was a single-center study, only a single biomarker was analyzed, and sample size was not large enough to stratify data according to cardiac lesion or AKI stage. We recognize that the physiologic (and ischemic) implications of different congenital heart diseases may be critically important not only to the risk posed for injury to the kidney, but also may have significant implications as to the underlying renal function [11,13,18,24,27,29]. In children, uNGAL's ability to predict AKI is enhanced when it is used in combination with other biomarkers for renal injury or function such as interleukin-18 (IL-18), Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinases 1 (TIMP-1) [29,31].…”

Commentary: Predicting acute kidney injury in pediatric cardiac surgery

“…Therefore, as Penk and colleagues 1 point out clearly, a prospective trial validating the furosemide stress test in the pediatric population is a critical next step. Such a trial should monitor early urinary biomarkers validated in the pediatric cardiac surgical population, 3,4 such as neutrophil gelatinase-associated lipocalin, markers of cell cycle arrest (tissue inhibitor of metalloproteinase combined with insulin-like growth factor-binding protein 7), and plasma cystatin C. 5 Ideally, an optimal combination of biomarkers and functional studies would predict AKI early and with high reliability, thus allowing modulation of intraoperative and perioperative renal protection strategies.…”