Severe acute kidney injury in neonates with necrotizing enterocolitis: risk factors and outcomes

Abstract

Background

To study the risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis.

Methods

Retrospective chart review of 202 neonates with necrotizing enterocolitis (NEC) (Bell stage >IIa) from 2013 to 2018. AKI was defined as per-modified neonatal Kidney Disease: Improving Global Outcomes criteria. Demographic, clinical, and outcome data were compared between neonates without severe AKI (stage 0 and 1 AKI) and those with severe AKI (stage 2 and 3 AKI).

Results

Severe AKI occurred in 66/202 (32.6%) of neonates after NEC diagnosis and after 61/104 (58.7%) of surgical NEC diagnoses. On adjusted model, surgical NEC [adjusted odds ratio (aOR) = 30.6; 95% confidence interval (CI) = 8.9, 130.6], outborn [aOR = 3.9; 95% CI = 1.54, 11.0], exposure to antenatal steroids [aOR = 3.0; 95% CI = 1.1, 8.9], and positive blood culture sepsis [aOR = 3.5; 95% CI = 1.3, 10.0] had increased odds for severe AKI. Those with severe AKI required longer hospitalization [124 days (interquartile range (IQR) 88–187) vs. 82 days (IQR 42–126), p < 0.001].

Conclusions

Severe AKI is common in neonates with NEC who require surgical intervention, are outborn, have positive blood culture sepsis, and receive antenatal steroids. Severe AKI is associated with a significantly longer length of hospitalization.

Impact

  • Neonates with NEC, who are transferred from outside hospitals, require surgical NEC management, and/or have a positive blood culture at NEC onset are at the highest odds for severe (stages 2 and 3) AKI.

  • Assessment of urine output is important for patients with NEC. Without it, 11% of those with severe AKI would have been misdiagnosed using serum creatinine alone.

  • Kidney-protective strategies in the pre-, peri-, and postoperative period may improve the morbidity and mortality associated with severe AKI in neonates with NEC.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1

References

  1. 1.

    Neu, J. & Walker, W. A. Necrotizing enterocolitis. N. Engl. J. Med. 364, 255–264 (2011).

    CAS  Article  Google Scholar 

  2. 2.

    Sankaran, K. et al. Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units. J. Pediatr. Gastroenterol. Nutr. 39, 366–372 (2004).

    Article  Google Scholar 

  3. 3.

    Sjoberg Bexelius, T. et al. Intestinal failure after necrotising enterocolitis: incidence and risk factors in a Swedish population-based longitudinal study. BMJ Paediatr. Open 2, e000316 (2018).

    Article  Google Scholar 

  4. 4.

    Allin, B. S. R. et al. One-year outcomes following surgery for necrotising enterocolitis: a UK-wide cohort study. Arch. Dis. Child Fetal Neonatal Ed. 103, F461–f466 (2018).

    Article  Google Scholar 

  5. 5.

    Knell, J. et al. Current status of necrotizing enterocolitis. Curr. Probl. Surg. 56, 11–38 (2019).

    Article  Google Scholar 

  6. 6.

    Stoll, B. J. et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 314, 1039–1051 (2015).

    CAS  Article  Google Scholar 

  7. 7.

    Santulli, T. V. et al. Acute necrotizing enterocolitis in infancy: a review of 64 cases. Pediatrics 55, 376–387 (1975).

    CAS  PubMed  Google Scholar 

  8. 8.

    Mowitz, M. E., Dukhovny, D. & Zupancic, J. A. F. The cost of necrotizing enterocolitis in premature infants. Semin. Fetal Neonatal Med. 23, 416–419 (2018).

    Article  Google Scholar 

  9. 9.

    Ganapathy, V. et al. Long term healthcare costs of infants who survived neonatal necrotizing enterocolitis: a retrospective longitudinal study among infants enrolled in Texas Medicaid. BMC Pediatr. 13, 127 (2013).

    Article  Google Scholar 

  10. 10.

    Bao, Y. W. et al. Kidney disease models: tools to identify mechanisms and potential therapeutic targets. Zool. Res. 39, 72–86 (2018).

    Article  Google Scholar 

  11. 11.

    Garg, P. M. et al. Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins. Pediatr. Res. 78, 527–532 (2015).

    CAS  Article  Google Scholar 

  12. 12.

    Jetton, J. G. et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc. Health 1, 184–194 (2017).

    Article  Google Scholar 

  13. 13.

    Charlton, J. R. et al. Incidence and risk factors of early onset neonatal AKI. Clin. J. Am. Soc. Nephrol. 14, 184–195 (2019).

    Article  Google Scholar 

  14. 14.

    Wu, Y. et al. Incidence, risk factors, and outcomes of acute kidney injury in neonates after surgical procedures. Pediatr. Nephrol. 35, 1341–1346 (2020).

    Article  Google Scholar 

  15. 15.

    Mallory, P. P. et al. Acute kidney injury, fluid overload, and outcomes in children supported with extracorporeal membrane oxygenation for a respiratory indication. Asaio J. 66, 319–326 (2020).

    Article  Google Scholar 

  16. 16.

    Starr, M. C. et al. Acute kidney injury and bronchopulmonary dysplasia in premature neonates born less than 32 weeks’ gestation. Am. J. Perinatol. 37, 341–348 (2020).

    Article  Google Scholar 

  17. 17.

    Stoops, C. et al. The association of intraventricular hemorrhage and acute kidney injury in premature infants from the Assessment of the Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study. Neonatology 116, 321–330 (2019).

    Article  Google Scholar 

  18. 18.

    Criss, C. N. et al. Acute kidney injury in necrotizing enterocolitis predicts mortality. Pediatr. Nephrol. 33, 503–510 (2018).

    Article  Google Scholar 

  19. 19.

    Bakhoum, C. Y. et al. Acute kidney injury in preterm infants with necrotizing enterocolitis. J. Matern. Fetal Neonatal Med. 32, 3185–3190 (2019).

    Article  Google Scholar 

  20. 20.

    Sanchez, C., Garcia, M. A. & Valdes, B. D. Acute kidney injury in newborns with necrotizing enterocolitis: risk factors and mortality. Bol. Med Hosp. Infant Mex. 76, 210–214 (2019).

    PubMed  Google Scholar 

  21. 21.

    Bell, M. J. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg. 187, 1–7 (1978).

    CAS  Article  Google Scholar 

  22. 22.

    Lambert, D. K. et al. Fulminant necrotizing enterocolitis in a multihospital healthcare system. J. Perinatol. 32, 194–198 (2012).

    CAS  Article  Google Scholar 

  23. 23.

    Selewski, D. T. et al. Neonatal acute kidney injury. Pediatrics 136, e463–e473 (2015).

    Article  Google Scholar 

  24. 24.

    Jetton, J. G. et al. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: design of a Retrospective Cohort Study. Front. Pediatr. 4, 68 (2016).

    Article  Google Scholar 

  25. 25.

    Jetton, J. G. & Askenazi, D. J. Acute kidney injury in the neonate. Clin. Perinatol. 41, 487–502 (2014).

    Article  Google Scholar 

  26. 26.

    Zappitelli, M. et al. Developing a neonatal acute kidney injury research definition: a report from the NIDDK neonatal AKI workshop. Pediatr. Res. 82, 569–573 (2017).

    Article  Google Scholar 

  27. 27.

    Basu, R. K. et al. Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): a prospective study to improve diagnostic precision. J. Clin. Trials 5, 222 (2015).

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Kaddourah, A. et al. Epidemiology of acute kidney injury in critically ill children and young adults. N. Engl. J. Med. 376, 11–20 (2017).

    Article  Google Scholar 

  29. 29.

    Salerno, S. N. et al. Association between nephrotoxic drug combinations and acute kidney injury in the neonatal intensive care unit. J. Pediatr. S0022-3476(20)31021-0 https://doi.org/10.1016/j.jpeds.2020.08.035 (2020).

  30. 30.

    Alkandari, O. et al. Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit. Care 15, R146 (2011).

    Article  Google Scholar 

  31. 31.

    Kirkley, M. J. et al. Acute kidney injury in neonatal encephalopathy: an evaluation of the AWAKEN database. Pediatr. Nephrol. 34, 169–176 (2019).

    Article  Google Scholar 

  32. 32.

    Hashem, R. H. et al. Doppler ultrasound assessment of the splanchnic circulation in preterms with neonatal sepsis at risk for necrotizing enterocolitis. J. Ultrasound 20, 59–67 (2017).

    Article  Google Scholar 

  33. 33.

    Robertson, C. C. et al. An investigation of APOL1 risk genotypes and preterm birth in African American population cohorts. Nephrol. Dial. Transplant. 32, 2051–2058 (2017).

  34. 34.

    Preterm Birth. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm (2018).

  35. 35.

    South, A. M. et al. Renal function and blood pressure are altered in adolescents born preterm. Pediatr. Nephrol. 34, 137–144 (2019).

    Article  Google Scholar 

Download references

Acknowledgements

Dr. Keia Sanderson is supported by Grant 2015213 from the Doris Duke Charitable Foundation.

Author information

Affiliations

Authors

Contributions

P.M.G. designed the study; P.M.G., A.B.B., S.S., D.K.B., J.L.P., N.B.O., M.A.Y.A., K.R.S., and D.A. collected and analyzed the data; P.M.G., D.A., M.A.Y.A., and K.R.S. wrote the manuscript. All the authors contributed to and approved the manuscript.

Corresponding author

Correspondence to Parvesh Mohan Garg.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Garg, P.M., Britt, A.B., Ansari, M.A.Y. et al. Severe acute kidney injury in neonates with necrotizing enterocolitis: risk factors and outcomes. Pediatr Res (2021). https://doi.org/10.1038/s41390-020-01320-6

Download citation

Search

Quick links