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The case of neonatal acute kidney injury

The case of neonatal acute kidney injury: Don’t forget the babies!

 David J. AskenaziDepartment of Pediatrics, Division of Pediatric Nephrology, University of Alabama at Birmingham, Birmingham, USA Jennifer R. CharltonUniversity of Virginia Children’s Hospital, Charlottesville, Virginia, USA Ronnie GuilletMD, Golisano Children’s Hospital, University of Rochester, Rochester, New York, USA

Extraordinary advances in neonatal care have markedly reduced the mortality of infants hospitalized in neonatal intensive care units (NICU). In the last few years, more publications, presentations and workshops have focused on kidney health in the NICU and its potential long-term renal health implications. Multiple single center reports suggest that neonatal acute kidney injury (AKI) is common and portends poor outcomes. These data are consistent with publications in adults and children suggesting that critically-ill patients do not just die from AKI, rather, AKI and fluid overload directly impact outcomes.1 Neonatal AKI is not only associated with increased mortality and length of stay,2 there is expanding evidence that NICU graduates are at risk of chronic kidney disease (CKD).

CKD affects millions of children and adults across the world and, like many adulthood diseases, may have its origins in early life. NICU graduates are at risk of developing CKD. Yet, the magnitude, underlying risk factors, and pathophysiology of the problem have not been fully elucidated. Existing studies suggest CKD in NICU survivors may be due to antenatal factors and postnatal exposures. Because glomerulogenesis continues into 34-36 weeks of post-conception, premature delivery disrupts nephrogenesis, leaving premature infants ‘primed’ for AKI and CKD.3 Previously, it was assumed that after an episode of AKI the kidney would recover kidney function completely. However, recent data from animals, children and adults with AKI suggest that survivors are indeed at risk of developing CKD.4 The full impact of AKI events during the first weeks of life on long-term kidney and health outcomes is not yet known.

Given the current state of AKI knowledge and the unique conditions of the neonate in the ICU, multiple questions about neonatal kidney health remain unanswered. Which neonates are at most risk of AKI and CKD? How do we improve our ability to recognize neonatal AKI earlier in the disease process? What clinical risk factors, nutritional, genetic, and environmental factors determine kidney health and/or disease? How do we recognize and prevent fluid overload in critically-ill neonates? What interventions can be used to prevent AKI and CKD and the consequences of failed organ function? What is the role of renal support devices in the care of critically-ill neonates with multi-organ failure? How is neonatal AKI different in those born in developed vs underdeveloped countries?

To answer these questions, several exciting initiatives are underway which promise to improve our understanding of neonatal AKI and enhance our ability to care for neonates with AKI. Groups such as the Neonatal Kidney Collaborative (neonatologists and pediatric nephrologists dedicated to improving neonatal kidney health) have formed and are conducting research on large international multi-center cohort studies. The NKC recently completed a 24-center multi-institutional study called Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN)5. Data from over 2000 sick neonates (born in 4 countries, across 24 centers) will allow investigators to understand the magnitude of the problem and have ample power to test whether AKI indeed portends poor outcomes after controlling for potential confounding variables. New devices, specifically designed to provide renal support therapy for neonates, have been developed and are currently being tested. These devices promise to enhance the ability to provide safe and reliable care to even the smallest infants. These advances will help improve the clinician’s ability to prevent, treat, support and prognosticate outcomes in vulnerable neonates at risk of kidney disease.

  1. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, AWARE Investigators. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N.Engl.J.Med. 2017;376:11-20

  2. Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, et al. Neonatal Acute Kidney Injury. Pediatrics 2015;136:e463-73

  3. Carmody JB, Charlton JR. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics 2013;131:1168-79

  4. Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int. 2012;82:516-24

  5. Jetton JG, Guillet R, Askenazi DJ, Dill L, Jacobs J, Kent AL, et al. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study. Front.Pediatr. 2016;4:6


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