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Maternal and environmental risk factors for neonatal AKI and its long-term consequences

Nature Reviews Nephrology volume 14, pages 688–703 (2018)Cite this article

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Abstract

Acute kidney injury (AKI) is a common and life-threatening complication in critically ill neonates. Gestational risk factors for AKI include premature birth, intrauterine growth restriction and low birthweight, which are associated with poor nephron development and are often the consequence of pre-gestational and gestational factors, such as poor nutritional status. Our understanding of how to best optimize renal development and prevent AKI is in its infancy; however, the identification of pre-gestational and gestational factors that increase the risk of adverse neonatal outcomes and the implementation of interventions, such as improving nutritional status early in pregnancy, have the potential to optimize fetal growth and reduce the risk of preterm birth, thereby improving kidney health. The overall risk of AKI among critically ill and premature neonates is exacerbated postnatally as these infants are often exposed to dehydration, septic shock and potentially nephrotoxic medications. Strategies to improve outcomes — for example, through careful evaluation of nephrotoxic drugs — may reduce the incidence of AKI and its consequences among this population. Management strategies and updated technology that will support neonates with AKI are greatly needed. Extremely premature infants and those who survive an episode of AKI should be screened for chronic kidney disease until early adulthood. Here, we provide an overview of our current understanding of neonatal AKI, focusing on its relationship to preterm birth and growth restriction. We describe factors that prevent optimal nephrogenesis during pregnancy and provide a framework for future explorations designed to maximize outcomes in this vulnerable population.

Key points

  • Even after controlling for multiple potential confounders, acute kidney injury (AKI) is an important determinant of morbidity and mortality in critically ill neonates.

  • Prematurity and low birthweight (LBW), which are surrogate indices of reduced nephron endowment, might predispose neonates to AKI.

  • Prematurity and LBW are associated with several comorbidities that are themselves risk factors for AKI in neonates.

  • Neonates with critical illness, especially those born prematurely, often receive medications that might increase susceptibility to toxic renal injury and risk of AKI.

  • The identification of pre-gestational risk factors and early intervention during pregnancy, especially in the context of maternal nutrition, as well as careful evaluation of infant exposure to nephrotoxic medications, might limit neonatal AKI, although further research is required to optimize renal development in premature infants and support neonates with AKI.

  • Neonates who survive AKI might experience long-term renal dysfunction and should be monitored and screened periodically for chronic kidney disease throughout childhood and young-adult life.

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Fig. 1: Changes in serum creatinine concentrations over the first 52 days of life in preterm neonates (gestational age (GA) <27 weeks and 31–32 weeks).
Fig. 2: Maternal diet regulates epigenetic processes that influence fetal growth as demonstrated by studies in mice fed a low-protein diet during early gestation.
Fig. 3: Pre-gestational and gestational risk factors for intrauterine growth restriction, low birthweight and preterm birth, which are associated with impaired renal development and low nephron number.

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Authors and Affiliations

  1. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy

    Norberto Perico, Monica Cortinovis & Giuseppe Remuzzi

  2. Pediatric and Infant Center for Acute Nephrology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    David Askenazi

  3. Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

    Giuseppe Remuzzi

  4. L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

    Giuseppe Remuzzi

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  1. Norberto Perico
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  2. David Askenazi
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N.P. and M.C. researched data for the article. N.P. and G.R. discussed how to organize the manuscript and which topics to cover. N.P. and M.C. wrote the first draft of the manuscript, which was reviewed, implemented and edited by D.A. and G.R. before submission.

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Glossary

Chorioamnionitis

Also known as intra-amniotic infection, it is an inflammation of the fetal membranes (amnion and chorion) due to a bacterial infection.

Hypocomplementaemia

A condition in which one of the components of complement is lacking or reduced in the blood.

Spontaneously conceived

Conception without the use of any medical interventions; also referred to as natural conception.

Peripartum period

The peripartum period spans from the last month of gestation to 5 months after delivery.

Perinatal asphyxia

Also known as birth asphyxia, it is the failure to initiate and sustain respiration at birth.

Diaphragmatic hernia

The presence of a defect in the diaphragm that allows herniation of some abdominal viscera into the thoracic cavity, causing respiratory distress at birth with or without pulmonary hypoplasia and/or hypertension.

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Perico, N., Askenazi, D., Cortinovis, M. et al. Maternal and environmental risk factors for neonatal AKI and its long-term consequences. Nat Rev Nephrol 14, 688–703 (2018). https://doi.org/10.1038/s41581-018-0054-y

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