• 1.

    Chaturvedi S, et al. The path to chronic kidney disease following acute kidney injury: A neonatal perspective. Pediatr Nephrol 2017; 32:227241. doi: 10.1007/s00467-015-3298-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Crump C, et al. Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: National cohort study. BMJ 2019; 365:l1346. doi: 10.1136/bmj.l1346

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Gjerde A, et al. Intrauterine growth restriction and risk of diverse forms of kidney disease during the first 50 years of life. Clin J Am Soc Nephrol 2020; 15:14131423. doi: 10.2215/CJN.04080320

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Harer MW, et al. Follow-up of acute kidney injury in neonates during childhood years (FANCY): A prospective cohort study. Pediatr Nephrol 2017; 32:10671076. doi: 10.1007/s00467-017-3603-x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Sanderson KR, et al. Albuminuria, hypertension, and reduced kidney volumes in adolescents born extremely premature. Front Pediatr 2020; 8:230. doi: 10.3389/fped.2020.00230

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Brenner BM, et al. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1988; 1:335347. doi: 10.1093/ajh/1.4.335

  • 7.

    Hingorani S, et al. Prevalence and risk factors for kidney disease and elevated BP in 2-year-old children born extremely premature. Clin J Am Soc Nephrol [published online ahead of print July 19, 2022]. doi: 10.2215/CJN.15011121; https://cjasn.asnjournals.org/content/17/8/1129

    • Search Google Scholar
    • Export Citation
  • 8.

    ClinicalTrials.gov. Preterm Erythropoietin Neuroprotection Trial (PENUT Trial) (PENUT). https://clinicaltrials.gov/ct2/show/NCT01378273

Extreme Prematurity and Kidney Outcomes: Should We Care?

Tahagod MohamedTahagod Mohamed, MD, is the Neonatal Nephrology Program Director in The Kidney and Urinary Tract Center at Nationwide Children's Hospital and an Assistant Professor of Pediatrics at The Ohio State University College of Medicine, Columbus. Michelle Starr, MD, holds joint appointments in Pediatric Nephrology and Pediatric and Adolescent Comparative Effectiveness Research at Riley Children's Health and is an Assistant Professor of Pediatrics at Indiana University School of Medicine, Indianapolis.

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Michelle StarrTahagod Mohamed, MD, is the Neonatal Nephrology Program Director in The Kidney and Urinary Tract Center at Nationwide Children's Hospital and an Assistant Professor of Pediatrics at The Ohio State University College of Medicine, Columbus. Michelle Starr, MD, holds joint appointments in Pediatric Nephrology and Pediatric and Adolescent Comparative Effectiveness Research at Riley Children's Health and is an Assistant Professor of Pediatrics at Indiana University School of Medicine, Indianapolis.

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Knowledge of the impact of extreme prematurity on long-term kidney outcomes is quickly evolving (1, 2). Several previous studies reported an association of extreme prematurity with worse kidney outcomes in children and adults (15). Kidney outcomes are particularly worrisome in children born at <28 weeks of gestation (often referred to as extremely low gestational age neonates or ELGANs) and in very low birthweight infants (<1500 g). These infants are likely to have the lowest nephron number due to premature birth and resulting incomplete and/or abnormal nephrogenesis (6). Previously studied kidney outcomes included abnormal kidney function, as evidenced by abnormal estimated glomerular filtration rate (eGFR), proteinuria, and hypertension. However, the onset of these findings is not fully characterized. There are currently no expert recommendations for when to initiate screening and evaluation for kidney diseases in former ELGANs. Some studies (4) suggest that chronic kidney disease (CKD) in former extremely preterm children can be detectable as early as school age. Other reports show evidence of CKD in adolescence (5) or later in life when former extremely preterm individuals are followed for several decades (2, 3).

Hingorani and colleagues (7) further explore this question using the Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) cohort. REPAIReD evaluated kidney outcomes in ELGANs enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT), a prospective multicenter study (8). Hingorani et al. (7) report the prevalence and risk factors of kidney diseases and hypertension at 2 years of age in former ELGANs. The study is unique in evaluating kidney outcomes at an early age in former ELGANS (n = 565). At 2 years old, more than one-half of participants (53%) had evidence of kidney diseases, including CKD, as evidenced by abnormal eGFR (18%), albuminuria (36%), and systolic (22%) and diastolic (44%) hypertension. Younger gestational age, smaller birthweight, and treatment with prenatal steroids were associated with increased risk of CKD. Factors that associated with increased risk of hypertension included male sex, Black race, treatment with indomethacin, and neonatal acute kidney injury.

These findings have implications for the kidney care of ELGANs. They provide insight into inpatient care and long-term follow-up of kidney health for former ELGANs. Robust patient education before discharge from the neonatal intensive care unit (NICU) about the risks of long-term kidney diseases and the need for monitoring can play a role in improving family awareness. Documentation of the risk of kidney diseases in patient health records is also important to promote regular blood pressure evaluation at each pediatrician visit. Follow-up with a nephrologist may be warranted for some children, especially those with a history of acute kidney injury or any other kidney-related complication (e.g., hypertension) during NICU admission. Research is needed to allow longitudinal follow-up of former ELGANs after graduation from the NICU to better define the natural course of prematurity-associated kidney diseases and the optimal timing for initiation and interval of follow-up and screening for kidney diseases in former ELGANs.

References

  • 1.

    Chaturvedi S, et al. The path to chronic kidney disease following acute kidney injury: A neonatal perspective. Pediatr Nephrol 2017; 32:227241. doi: 10.1007/s00467-015-3298-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Crump C, et al. Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: National cohort study. BMJ 2019; 365:l1346. doi: 10.1136/bmj.l1346

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Gjerde A, et al. Intrauterine growth restriction and risk of diverse forms of kidney disease during the first 50 years of life. Clin J Am Soc Nephrol 2020; 15:14131423. doi: 10.2215/CJN.04080320

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Harer MW, et al. Follow-up of acute kidney injury in neonates during childhood years (FANCY): A prospective cohort study. Pediatr Nephrol 2017; 32:10671076. doi: 10.1007/s00467-017-3603-x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Sanderson KR, et al. Albuminuria, hypertension, and reduced kidney volumes in adolescents born extremely premature. Front Pediatr 2020; 8:230. doi: 10.3389/fped.2020.00230

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Brenner BM, et al. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1988; 1:335347. doi: 10.1093/ajh/1.4.335

  • 7.

    Hingorani S, et al. Prevalence and risk factors for kidney disease and elevated BP in 2-year-old children born extremely premature. Clin J Am Soc Nephrol [published online ahead of print July 19, 2022]. doi: 10.2215/CJN.15011121; https://cjasn.asnjournals.org/content/17/8/1129

    • Search Google Scholar
    • Export Citation
  • 8.

    ClinicalTrials.gov. Preterm Erythropoietin Neuroprotection Trial (PENUT Trial) (PENUT). https://clinicaltrials.gov/ct2/show/NCT01378273

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