Article of the Month - Jul 2022

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature

CJASN Jul 2022, CJN.15011121. doi:10.2215/CJN.15011121

Sangeeta Hingorani, Robert Schmicker, Kaashif A. Ahmad, Ivan D. Frantz, Dennis E. Mayock, Edmund F. La Gamma, Mariana Baserga, Janine Y. Khan, Maureen M. Gilmore, Tonya Robinson, Patrick Brophy, Patrick J. Heagerty, Sandra E. Juul, Stuart Goldstein, David Askenazi

Reviewed by: Paige Condit


A neonate’s experience and exposures in the NICU have been linked to long term health conditions such as obesity and coronary artery disease. Many different factors in the NICU including gestational age, birth weight, and nephro-influential factors (medications, hypoxemia, fluid restriction, etc.) affect kidney function both acutely and long term. Recently a study showed an increased risk of CKD in the first 9 years of life for children born at less than 28 weeks gestational age, but nuance regarding the interplay between specific risk factors and kidney disease as well as timing of kidney dysfunction development post-NICU stay is unknown.

What was the purpose of the study?

The goal of this study was to report the prevalence of 2-year kidney outcomes for infants born at less than 28 weeks gestational age and evaluate risk factors that may lead to adverse kidney outcomes.

What were the study design and methods?

The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study was an ancillary study to the Preterm Epo Neuroprotection Trial (PENUT). Families with neonates born between 24 – 27 6/7 weeks gestation who were participating in PENUT were approached and consented to participate in REPAIReD.

Serum and urine were collected based on the study protocol and again at a 2-year follow up visit. AKI defined by the SCr component of the KDIGO definition was determined using SCr collected as routine clinical care while the infants were inpatient.

At the 2-year follow up visit kidney disease was assessed looking at eGFR < 90 ml/min per 1.73 m2 calculated using the CKiDU25 equation, albuminuria defined as ACR3 30 mg albumin/g creatinine, and systolic and diastolic BP > 90th percentile for age and sex based on the 2017 definitions.

What are the results?

565 patients from the total PENUT cohort of 923 were included in REPAIReD. 51% were male, 25% were 24 weeks GA, 24% were 25 weeks GA, 24% were 26 weeks GA, and 27% were 27 weeks GA.

eGFR at 2 years

  • 42% of the cohort had blood available at 2 years for eGFR analysis.
  • 18% of the overall cohort had eGFR < 90 ml/min per 1.73 m2.
  • Older gestational ages and higher birthweight were associated with lower odds of eGFR < 90 ml/min per 1.73 m2.
  • SGA status, maternal preeclampsia, prenatal steroid exposure, and vasopressor use were associated with an increased odds of eGFR < 90 ml/min per 1.73 m2.

ACR at 2 years

  • 52% of the cohort had urine at 2 years to allow for ACR calculation.
  • Black maternal race was associated with increased rates of albuminuria.
  • No other differences between variables were seen.

BP at 2 years

  • 35% of the cohort had 2 blood pressure readings at 2 years.
  • Elevated diastolic BP was more likely in males and in those who experienced severe AKI while in the NICU
  • Indomethacin exposure and children who gained more weight while in the NICU were more likely to have an elevated systolic and diastolic BP.

The strengths of this study are the large cohort size and the prospective nature. A limitation is the decreased rate of follow compared to the original PENUT cohort.

What was the conclusion?

Infants born at < 28 weeks gestation had increased prevalence of adverse kidney outcomes at 2 years of age. The prevalence was independent of whether the infant experienced AKI or amongst infants with alterations in cystatin C and Cr levels throughout their NICU stay, indicating the long-term adverse outcome prevalence may be secondary to intrinsic kidney differences from prematurity and potentially not related to the NICU experience.

Why is this important?

Recommendations for long-term monitoring related to kidney function are not well defined for NICU grads. This study supports approaches including family awareness of the risk of kidney dysfunction in childhood and long term monitoring of kidney function, which may incorporate blood pressure monitoring as well as serum and urinary markers.