Clinical impact of severe acute kidney injury on post-operative and brain injury outcomes in preterm infants following surgical necrotizing enterocolitis

Abstract

Background

To evaluate post-operative outcomes and white matter injury (WMI) using brain MRI at term equivalent in neonates with and without severe acute kidney injury (AKI) following surgical necrotizing enterocolitis (NEC).

Methods

A retrospective cohort study comparing neonates with severe (Stage 2/3) vs. other (no AKI/Stage 1) AKI using KDIGO classification with multivariable models assessing this association in the context of multiple systemic comorbidities.

Results

Of 103 neonates with surgical NEC, 60 (58%) had severe AKI. Those with severe AKI had lower birth weight (BW; 715 vs. 950 g; p = .023), more frequently treated with indomethacin (18.3 vs. 2.4%); p = .014), higher CRP levels at 24 h after NEC onset (14.4 [6.4–19.8] vs. 4.8 [1.6–13.4]; p = .005), higher presence of cholestasis (73.3 vs. 51.2%); p = .023), later age of NEC onset (14 vs. 7 d); p = .004), longer length of bowel resected (14.9 vs. 4.3 cm); p = .011), longer post-operative ileus days (14 vs. 9 d); p < .001), longer post-operative days at starting enteral feedings (15 vs. 10 d; p < .001), longer days of attainment of full enteral feedings (75 vs. 44.5 d; p = .008) and longer length of stay (140.5 vs. 94 d; p = .028) compared to those without severe AKI. Compared to infants without AKI by serum creatinine, those with AKI had significantly more cases of white matter abnormality (WMA; 90 vs. 36.6%; p < .001) and retinopathy of prematurity (63.9 vs. 35.3%; p = .017). In addition, the presence of AKI Stage 2 and 3 by serum creatinine was independently associated with higher odds of sustaining severe WMI level on an ordinal scale (OR = 6.2; 95% CI = (1.1–35.5); p = .041).

Conclusions

Neonates with severe AKI following surgical NEC were more likely to experience longer post-operative morbidity and higher WMI by MRI at term.

Keywords:

• Acute kidney injury
• brain injury
• postoperative outcomes
• preterm infants

Future direction

In the future, both retrospective and prospective studies (particularly multi-center to enhance sample size) with additional clinical data (e.g. end-organ (kidney and brain) perfusion by near-infrared spectroscopy [51]) and functional/tubular urinary and brain biomarkers, which may help providers predict AKI and brain injury at an early stage. Studies that evaluate kidney protective strategies to prevent AKI and neuroprotective strategies to prevent brain injury and its consequences are needed to improve the post-operative recovery clinical and neurodevelopmental outcomes in neonates with surgical NEC. There is a need to develop a scoring system including AKI to identify the high-risk neonates with advanced NEC and develop improved therapeutic options. These high-risk infants with severe AKI should be followed post-discharge with a pediatric nephrologist and developmental specialist to identify long-term sequela, including chronic kidney disease.

Category of study

Clinical science.

Informed consent

Patient consent was not required as per IRB.

Disclosure statement

The authors disclose no conflicts. All authors declare no real or perceived conflicts of interest that could affect the study design, collection, analysis, and interpretation of data, writing of the report, or the decision to submit for publication. PMG designed the study; PMG, AB, JP, DA collected and analyzed the data; MZ and WBH participated in the data analysis. PMG, DA, MZ, WBH, JFP, and KS wrote the article. All the authors approved the manuscript. For full disclosure, we provide here an additional list of other author’s commitments and funding sources that are not directly related to this study: David J Askenazi is a consultant for Baxter, Nuwellis, Medtronic Bioporto, the AKI Foundation, and SeaStar. In addition, he receives grant funding for education and studies not related to this project from Baxter, Nuwellis, and Medtronic. He has patents pending in the area of urine collection and kidney support therapy.

Additional information

Funding

William B. Hillegass, MD, Ph.D. is partially supported by the IDeA grant U54GM115428. Dr. Parvesh Garg is partially supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number U54GM115428. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and The Mississippi Center for Clinical and Translational Research for supporting NEC research and Mississippi IDeA Network of Biomedical Research Excellence.