Transient and persistent acute kidney injury phenotypes following the Norwood operation: a retrospective study

Abstract

Background: Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes. Methods: Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay. Results: One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004). Conclusions: Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children

“…Expert consensus and emerging data support the view that these elements combined with individual susceptibility contribute to unique, discernible AKI phenotypes in children with AKI (Figure 1B). In particular, evidence supports the use of clinical features such as urine output, severity and duration of creatinine elevation, fluid overload, response to loop diuretics, and tubular injury biomarkers, to refine AKI diagnosis and reveal unique phenotypes. The concept of subclinical AKI is defined by an elevation in a urine tubular injury biomarker without elevation in functional marker.…”

Subphenotypes of acute kidney injury in children

“…These studies have prompted investigators to evaluate the contribution of AKI duration for delineation of subphenotypes and the associations with outcomes as recommended by the 16th Acute Disease Quality Initiative (ADQI) [4]. Gist et al [21] compared the association of transient ( 48 h) and persistent (>48 h) in a two-center study of children with hypoplastic left heart syndrome. Mortality was four times higher (41 vs. 12%) in those with persistent AKI, although this association was not significant on multivariable analysis.…”

“…Table 1 outlines proposed relevant outcomes of interest for prognostic enrichment in AKI, potential use cases for such tools, and some existing examples, whenever applicable. Notably, there has been an appropriate focus on identifying tools to predict who will develop severe and/or persistent AKI, as there is a growing body of evidence suggesting an association between these outcomes and morbidity and mortality in both adults and children [1,4,21,31 ▪▪ ]. Importantly, utilization of prognostic enrichment tools designed to predict these outcomes may facilitate enrichment of future clinical trials aimed at preventing AKI (as has been done successfully in some adult studies) [52,53], and testing novel therapeutics, reducing the number of patients needed to enroll, and increasing the likelihood of seeing a benefit if one exists.…”

Modifying the Renal Angina Index for Predicting AKI and Related Adverse Outcomes in Pediatric Heart Surgery

“…Data indicate a large proportion of AKI after cardiac surgery is transient (resolves within 48 h), and that persistent AKI (evident early postoperative and remains present 48-72 h later) strongly weights the negative AKI-associated patient outcomes. 12,13 Furthermore, it is possible that some cases of AKI are initially subclinical, meaning that there is no rise in serum creatinine immediately after surgery, yet these patients still experience AKI-related poor outcomes including prolonged ventilation, length of stay, and death. Thus, identification of patients at risk for severe persistent AKI or its associated complications after pediatric cardiac surgery may facilitate population enrichment for targeting diagnostics and/or therapeutics.…”