(Screen 3 - 6:30 PM Friday) Identifying Kidney Injury via Urinary Biomarkers after the Comprehensive Stage II Palliation and Bidirectional Glenn procedure

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Abstract:

Introduction:
Single ventricle patients undergoing comprehensive stage II palliation (CS2) have a higher incidence of severe acute kidney injury (AKI) compared to the Bidirectional Glenn (BDG) palliation, however the best method for early detection remains unknown. The urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver fatty acid-binding protein (L-FABP), kidney injury molecule-1 (KIM-1), and Cystatin C have been shown to be increased in other patient populations with postoperative kidney injury. We hypothesize that NGAL, IL-18, L-FABP, KIM-1 and Cystatin C would be greater during the postoperative period in patients undergoing the CS2 than the BDG procedure.

Methods:
Prospective, observational study of 20 patients undergoing stage 2 palliation for single ventricle physiology between July 2019 and December 2021. AKI stage was defined by Kidney Diseases Improving Global Outcomes (KDIGO) criteria based on peak creatinine value up to post operative day 3. Urine samples were collected pre-operatively, 1, 6, and 24 hours after surgery. Urinary biomarker concentrations of NGAL, IL-18, L-FABP, KIM-1 and Cystatin C were determined using commercially available ELISA kits and normalized to urinary creatinine (CR). Nonparametric testing and Two-way ANOVA (mixed-effects model) was used to compare the biomarkers between the patients undergoing CS2 palliation and BDG with p < 0.05 considered significant.

Results:
BDG procedure was utilized for 12 patients while 8 patients underwent the CS2 palliation. 1/12 (8%) of patients that underwent BDG developed ≥ stage 2 AKI compared to 4/8 (50%) of patients that underwent CS2. NGAL levels peaked at one hour post-operatively and were greater in the CS2 group 1683 ng/mg Cr [IQR:356-1961] than in the BDG 48 ng/mg Cr [IQR:8-822] (p=0.05). L-FABP levels were also greater in the CS2 group at one hour post-operatively than in the BDG group (CS2 12836 ng/mg Cr [IQR 3008-23413] vs. BDG 1272 ng/mg Cr [IQR 204.4-7059], p=0.05). KIM-1 was greater in CS2 group than in the BDG group at 1, 6, and 24 hours (p=0.02, p=0.0008, and p=0.009 respectively), and peaked at 24 hours post-operatively with a median value of 10.7 ng/mg Cr [IQR:8.6-23.5] compared to 2.4 ng/mg Cr [IQR:1-7]. Comparison of measured NGAL and KIM-1 between patients undergoing CS2 and BDG palliation are shown in Figure 1. There was no significant difference for Cystatin C and IL-18.

Conclusions:
Infants undergoing CS2 palliation had significantly higher levels of NGAL, L-FABP and KIM-1 compared to the BDG palliation. NGAL, L-FABP and KIM-1 may be more useful than Cystatin C and IL-18 in the early detection of AKI following CS2 palliation.