Background

Fetuses are born with fully developed kidneys in the womb. The glomeruli complete development around 36 weeks of gestation and are not newly formed after birth. For this reason, premature infants, who are born prematurely, have a higher risk of developing chronic kidney disease (CKD) in adulthood due to a lack of glomeruli. However, the renal health of term small for gestational age (SGA) infants, who have a birth weight below the 10th percentile despite reaching full term, has been relatively understudied.

SGA, caused by intrauterine growth restriction, is likely to have a small kidney size and a reduced number of glomeruli. Podocytes, which form the filtration barrier of the glomeruli, are not regenerated once lost. The phenomenon in which these cells detach from the glomeruli and are excreted in the urine is an early sign of renal damage. Previous studies have reported that premature infants have a high rate of loss of podocyte-specific mRNA in their urine. However, it is not yet clear whether SGA infants also experience glomerular damage early in life.

Key Findings

A recent study meticulously tracked the trend of podocyte-specific mRNA loss in the urine of term SGA infants. The researchers designed a case-control study by collecting urine samples from a group of term SGA infants and a group of appropriate for gestational age (AGA) infants. They then used real-time quantitative polymerase chain reaction (RT-qPCR) to determine the levels of podocin mRNA, an indicator of podocyte damage. To correct for kidney function status, they calculated the urinary podocin mRNA-to-creatinine ratio (UpodCR).

The analysis revealed that term SGA infants had significantly higher levels of UpodCR in their urine compared to AGA infants. Statistical analysis showed that low birth weight and SGA status were independent risk factors for podocyte mRNA loss. In addition, the degree of podocyte mRNA loss in the urine was correlated with increased urinary protein (UP) and urinary microalbumin (UMA). This suggests that even though SGA infants are born at term, they experienced stress on the glomerular filtration barrier due to intrauterine growth restriction.

Significance and Prospects

This finding raises questions about the existing clinical practice for term SGA infants in the fields of pediatrics and nephrology. In the past, term SGA infants have been considered to have a lower risk of renal complications compared to premature infants and have often been excluded from monitoring. However, with the demonstration of early podocyte damage, there is a growing call for the establishment of a system for early renal follow-up of SGA children. UpodCR, a non-invasive test, is expected to become a tool for screening early renal dysfunction.

Although urine mRNA analysis sensitively detects glomerular damage, there are still challenges to be overcome before it can be fully implemented in clinical practice. As a single-center study, the sample size is limited, and there is a lack of long-term longitudinal data on podocyte loss during infancy. A large, prospective cohort study is needed to verify whether the incidence of CKD increases in SGA infants as they grow into childhood and adulthood.