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  • Clinical Research Article
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Preceding risks and mortality outcomes of different neonatal acute kidney injury in preterm infants



The aim of the study was to examine preceding risks and mortality outcomes of oliguric and non-oliguric acute kidney injury (AKI) in very preterm infants.


Infants born ≤30 weeks’ gestation were included. AKI was diagnosed based on neonatal Kidney Disease: Improving Global Outcomes criteria and was classified as oliguric and non-oliguric according to the urine-output criteria. We used modified Poisson and Cox proportional-hazards models for statistical comparisons.


Of 865 enrolled infants (gestational age 27.2 ± 2.2 weeks and birth weight 983 ± 288 gm), 204 (23.6%) developed AKI. Before AKI, the oliguric AKI group had significantly higher prevalence of small-for-gestational age (p = 0.008), lower 5-min Apgar score (p = 0.009) and acidosis (p = 0.009) on admission, and hypotension (p = 0.008) and sepsis (p = 0.001) during admission than the non-oliguric AKI group. Oliguric (adjusted risk ratio 3.58, 95% CI 2.33–5.51; adjusted hazard ratio 4.93, 95% CI 3.14–7.72) instead of non-oliguric AKI had significantly higher mortality risks than no AKI. Oliguric AKI showed significantly higher mortality risks than non-oliguric AKI, irrespective of serum creatinine and severity of AKI.


Categorizing AKI as oliguric and non-oliguric was crucial because of the distinct preceding risks and mortality outcomes of these two types of AKI in very preterm neonates.


  • The differences of the underlying risks and prognosis between oliguric and non-oliguric AKI in very preterm infants remain unclear.

  • We found that oliguric AKI, but not non-oliguric AKI, carries higher mortality risks than infants without AKI. Oliguric AKI possessed higher mortality risks than non-oliguric AKI, irrespective of concomitant serum creatinine elevation and severe AKI.

  • Oliguric AKI is more associated with prenatal small-for-the-gestational age and perinatal and postnatal adverse events, while non-oliguric AKI is associated with nephrotoxins exposures.

  • Our finding highlighted the importance of oliguric AKI and is helpful in developing future protocol in neonatal critical care.

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Data availability

The corresponding author had full access to the dataset used and analyzed during the current study. The datasets used during the current study are available from the corresponding author on reasonable request.


  1. Carmody, J. B., Swanson, J. R., Rhone, E. T. & Charlton, J. R. Recognition and reporting of AKI in very low birth weight infants. Clin. J. Am. Soc. Nephrol. 9, 2036–2043 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rodríguez, M. M. et al. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr. Dev. Pathol. 7, 17–25 (2004).

    Article  PubMed  Google Scholar 

  3. Luyckx, V. A. Preterm birth and its impact on renal health. Semin. Nephrol. 37, 311–319 (2017).

    Article  PubMed  Google Scholar 

  4. Menendez-Castro, C. et al. Neonatal nephron loss during active nephrogenesis - detrimental impact with long-term renal consequences. Sci. Rep. 8, 4542 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sutherland, M. R. et al. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J. Am. Soc. Nephrol. 22, 1365–1374 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kent, A. L. et al. Indomethacin, ibuprofen and gentamicin administered during late stages of glomerulogenesis do not reduce glomerular number at 14 days of age in the neonatal rat. Pediatr. Nephrol. 24, 1143–1149 (2009).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chen, C. C., Lin, Y. C., Wang, S. T. & Huang, C. C. Temporal trends of acute kidney injury and associated risk exposures in extremely preterm infants. Clin. J. Am. Soc. Nephrol. 16, 1169–1177 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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  PubMed  PubMed Central  Google Scholar 

  10. 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  PubMed  PubMed Central  Google Scholar 

  11. Charlton, J. R. et al. Late onset neonatal acute kidney injury: results from the Awaken Study. Pediatr. Res. 85, 339–348 (2019).

    Article  PubMed  Google Scholar 

  12. Bezerra, C. T., Vaz Cunha, L. C. & Libório, A. B. Defining reduced urine output in neonatal icu: importance for mortality and acute kidney injury classification. Nephrol. Dial. Transplant. 28, 901–909 (2013).

    Article  PubMed  Google Scholar 

  13. Elmas, A. T., Tabel, Y. & Özdemir, R. Risk factors and mortality rate in premature babies with acute kidney injury. J. Clin. Lab. Anal. 32, e22441 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gupta, B. D., Sharma, P., Bagla, J., Parakh, M. & Soni, J. P. Renal failure in asphyxiated neonates. Indian Pediatr. 42, 928–934 (2005).

    CAS  PubMed  Google Scholar 

  15. Viswanathan, S., Manyam, B., Azhibekov, T. & Mhanna, M. J. Risk factors associated with acute kidney injury in extremely low birth weight (ELBW) infants. Pediatr. Nephrol. 27, 303–311 (2012).

    Article  PubMed  Google Scholar 

  16. Wu, M. H. et al. Prevalence of congenital heart disease at live birth in Taiwan. J. Pediatr. 156, 782–785 (2010).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  18. Kaddourah, A., Basu, R. K., Bagshaw, S. M. & Goldstein, S. L. Epidemiology of acute kidney injury in critically ill children and young adults. N. Engl. J. Med. 376, 11–20 (2017).

    Article  PubMed  Google Scholar 

  19. Jadhav, P., Parimi, P. S. & Kalhan, S. C. Parenteral amino acid and metabolic acidosis in premature infants. JPEN J. Parenter. Enter. Nutr. 31, 278–283 (2007).

    Article  CAS  Google Scholar 

  20. Stoops, C. et al. Baby Ninja (nephrotoxic injury negated by just-in-time action): reduction of nephrotoxic medication-associated acute kidney injury in the neonatal intensive care unit. J. Pediatr. 215, 223.e6–228.e6 (2019).

    Article  Google Scholar 

  21. Azur, M. J., Stuart, E. A., Frangakis, C. & Leaf, P. J. Multiple imputation by chained equations: what is it and how does it work? Int. J. Methods Psychiatr. Res. 20, 40–49 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Blazek, K., van Zwieten, A., Saglimbene, V. & Teixeira-Pinto, A. A practical guide to multiple imputation of missing data in nephrology. Kidney Int. 99, 68–74 (2021).

    Article  PubMed  Google Scholar 

  23. Chen, W., Qian, L., Shi, J. & Franklin, M. Comparing performance between log-binomial and robust Poisson regression models for estimating risk ratios under model misspecification. BMC Med. Res. Methodol. 18, 63 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gubhaju, L. et al. Assessment of renal functional maturation and injury in preterm neonates during the first month of life. Am. J. Physiol. Ren. Physiol. 307, F149–F158 (2014).

    Article  CAS  Google Scholar 

  25. Liangos, O. Nonoliguric Versus Oliguric Acute Kidney Injury Post TW edn (UpToDate Inc., 2022).

  26. Honda, N. & Hishida, A. Pathophysiology of experimental nonoliguric acute renal failure. Kidney Int. 43, 513–521 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Carmody, J. B. & Charlton, J. R. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics 131, 1168–1179 (2013).

    Article  PubMed  Google Scholar 

  28. Behrendt, N. & Galan, H. L. Fetal growth in multiple gestations: evaluation and management. Obstet. Gynecol. Clin. North Am. 48, 401–417 (2021).

    Article  PubMed  Google Scholar 

  29. Perico, N., Askenazi, D., Cortinovis, M. & Remuzzi, G. Maternal and environmental risk factors for neonatal AKI and its long-term consequences. Nat. Rev. Nephrol. 14, 688–703 (2018).

    Article  CAS  PubMed  Google Scholar 

  30. Gallo, D., de Bijl-Marcus, K. A., Alderliesten, T., Lilien, M. & Groenendaal, F. Early acute kidney injury in preterm and term neonates: incidence, outcome, and associated clinical features. Neonatology 118, 174–179 (2021).

    Article  PubMed  Google Scholar 

  31. Starr, M. C. et al. Advances in neonatal acute kidney injury. Pediatrics 148, e2021051220 (2021).

  32. Schetz, M. & Hoste, E. Understanding oliguria in the critically ill. Intensive Care Med. 43, 914–916 (2017).

    Article  PubMed  Google Scholar 

  33. Mathis, M. R. et al. Preoperative risk and the association between hypotension and postoperative acute kidney injury. Anesthesiology 132, 461–475 (2020).

    Article  PubMed  Google Scholar 

  34. Izawa, J. et al. Early-phase cumulative hypotension duration and severe-stage progression in oliguric acute kidney injury with and without sepsis: an observational study. Crit. Care 20, 405 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hentschel, R., Lödige, B. & Bulla, M. Renal insufficiency in the neonatal period. Clin. Nephrol. 46, 54–58 (1996).

    CAS  PubMed  Google Scholar 

  36. Honore, P. M. et al. Prevention and treatment of sepsis-induced acute kidney injury: an update. Ann. Intensive Care 5, 51 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Rhone, E. T., Carmody, J. B., Swanson, J. R. & Charlton, J. R. Nephrotoxic medication exposure in very low birth weight infants. J. Matern. Fetal Neonatal Med. 27, 1485–1490 (2014).

    Article  CAS  PubMed  Google Scholar 

  38. Wu, I. M., Marin, E. P., Kashgarian, M. & Brewster, U. C. A case of an acute kidney injury secondary to an implanted aminoglycoside. Kidney Int. 75, 1109–1112 (2009).

    Article  PubMed  Google Scholar 

  39. Dixit, M., Doan, T., Kirschner, R. & Dixit, N. Significant acute kidney injury due to non-steroidal anti-inflammatory drugs: inpatient setting. Pharmaceuticals 3, 1279–1285 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kwiatkowska, E. et al. The mechanism of drug nephrotoxicity and the methods for preventing kidney damage. Int. J. Mol. Sci. 22, 6109 (2021).

  41. 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  PubMed  Google Scholar 

  42. Aziz, K. B., Schles, E. M., Makker, K. & Wynn, J. L. Frequency of acute kidney injury and association with mortality among extremely preterm infants. JAMA Netw. Open 5, e2246327 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kaddourah, A., Basu, R. K., Goldstein, S. L. & Sutherland, S. M. Oliguria and acute kidney injury in critically ill children: implications for diagnosis and outcomes. Pediatr. Crit. Care Med. 20, 332–339 (2019).

    Article  PubMed  Google Scholar 

  44. Alten, J. A. et al. Epidemiology of acute kidney injury after neonatal cardiac surgery: a report from the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network. Crit. Care Med. 49, e941–e951 (2021).

    Article  CAS  PubMed  Google Scholar 

  45. Doi, K. et al. The Japanese Clinical Practice Guideline for Acute Kidney Injury 2016. J. Intensive Care 6, 48 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Allegaert, K., Smits, A., Mekahli, D. & van den Anker, J. N. Creatinine at birth correlates with gestational age and birth weight: another factor of the imbroglio in early neonatal life. Neonatology 117, 637–640 (2020).

    Article  CAS  PubMed  Google Scholar 

  47. Gidi, N. W. et al. Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected nicus in Ethiopia. BMJ Paediatr. Open 4, e000765 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Vaara, S. T. et al. Association of oliguria with the development of acute kidney injury in the critically ill. Kidney Int. 89, 200–208 (2015).

  49. Mohsenin, V. Practical approach to detection and management of acute kidney injury in critically ill patient. J. Intensive Care 5, 57 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

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The authors thank the Taiwan Premature Baby Foundation and all team members in charge of data collection. None of these individuals were compensated for their contributions.


This study was supported by the grants from Taiwan Ministry of Science and Technology (MOST 110-2314-B-006-057, MOST-110-2314-B-006-113, MOST-109-2314-B-006-008) and from National Cheng Kung University Hospital (NCKUH-11001002, NCKUH-11101001).

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Authors and Affiliations



C.-C.C. and C.-C.H. contributed to research idea and study design; Y.-C.L. contributed to data acquisition; C.-C.C., C.-H.C., Y.-C.L., S.-T.W., and C.-C.H. contributed to data analysis/interpretation; C.-C.C., C.-H.C., and S.-T.W. provided statistical analysis; S.T.W. and C.C.H. provided supervision or mentorship. All authors contributed important intellectual content during manuscript drafting or revision.

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Correspondence to Chao-Ching Huang.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the ethics review board of National Cheng-Kung University Hospital (A-BR-108-013, and ER-98-135). The informed consent of participants born after August 13, 2009 was obtained and that of infants born previously were waived.

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Chen, CC., Chu, CH., Lin, YC. et al. Preceding risks and mortality outcomes of different neonatal acute kidney injury in preterm infants. Pediatr Res 94, 1530–1537 (2023).

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