Persistent acute kidney injury and fluid accumulation with outcomes after the Norwood procedure: report from NEPHRON

Abstract

Background: Cardiac surgery-associated acute kidney injury (CS-AKI) is common, but its impact on clinical outcomes is variable. Parsing AKI into sub-phenotype(s) and integrating pathologic positive cumulative fluid balance (CFB) may better inform prognosis. We sought to determine whether durational sub-phenotyping of CS-AKI with CFB strengthens association with outcomes among neonates undergoing the Norwood procedure.

Methods: Multicenter, retrospective cohort study from the Neonatal and Pediatric Heart and Renal Outcomes Network. Transient CS-AKI: present only on post-operative day (POD) 1 and/or 2; persistent CS-AKI: continued after POD 2. CFB was evaluated per day and peak CFB during the first 7 postoperative days. Primary and secondary outcomes were mortality, respiratory support-free and hospital-free days (at 28, 60 days, respectively). The primary predictor was persistent CS-AKI, defined by modified neonatal Kidney Disease: Improving Global Outcomes criteria.

Results: CS-AKI occurred in 59% (205/347) neonates: 36.6% (127/347) transient and 22.5% (78/347) persistent; CFB > 10% occurred in 18.7% (65/347). Patients with either persistent CS-AKI or peak CFB > 10% had higher mortality. Combined persistent CS-AKI with peak CFB > 10% (n = 21) associated with increased mortality (aOR: 7.8, 95% CI: 1.4, 45.5; p = 0.02), decreased respiratory support-free (predicted mean 12 vs. 19; p < 0.001) and hospital-free days (17 vs. 29; p = 0.048) compared to those with neither.

Conclusions: The combination of persistent CS-AKI and peak CFB > 10% after the Norwood procedure is associated with mortality and hospital resource utilization. Prospective studies targeting intra- and postoperative CS-AKI risk factors and reducing CFB have the potential to improve outcomes.

Keywords: Acute kidney injury; Database; Fluid; Neonatal; Norwood operation; Sub-phenotypes.

Fig. 1

Consort flow diagram. Patients divided by those included in the CS-AKI analyses and fluid balance analyses. Patients with CS-AKI are stratified by duration (transient and persistent). CFB was categorized into 2 groups, CFB > 5% on POD 1, and peak CFB > 10%. Abbreviations: NP – Norwood procedure, CS-AKI – cardiac surgery associated acute kidney injury, pts – patients, UOP – urine output, CFB – cumulative fluid balance, POD – postoperative day

Fig. 2

Odds ratio of mortality stratified by the combination of fluid metric and AKI subphenotype. Logistic regression models were used to calculate the odds ratio. The regression models included a persistent CS-AKI, peak CFB (> 10% vs. ≤ 10%) and the interaction term between persistent CS-AKI and peak CFB and b persistent CS-AKI, CFB on POD 1 (> 5% vs. ≤ 5%) and the interaction term between persistent CS-AKI and CFB on POD 1. The models are adjusted for post-op vasoactive inotrope score > 15 on POD 0 and major post-op complication or infection. This model accounts for the nesting of patients within hospitals via the Huber-While cluster sandwich estimator of variance. p values were calculated and compared to “no persistent + fluid metric” (as the reference group) with the other groups. Abbreviations: CS-AKI – cardiac surgery associated acute kidney injury, CFB – cumulative fluid balance, POD – postoperative day