Risk factors associated with a decreased estimated glomerular filtration rate based on cystatin C levels in school‐age children with extremely low birthweight

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In humans, although nephrogenesis starts around the 8th gestational week, 60% of nephrons are formed during the third trimester.1 Nephrogenesis is completed at 36 weeks' gestation,2 and these nephrons last for a lifetime. In premature infants, nephrogenesis continues until 40 days after birth, but does not reach the level of mature infants.3 Manalish et al. investigated neonates who died within 2 weeks of birth and found that low birthweight (LBW) infants had a significantly lower glomerular count and larger glomerular volume than normal birthweight infants.4 Brenner demonstrated that human glomerular counts, which are influenced by prematurity, are related to subsequent onset of chronic kidney disease (CKD).5 When the glomerular count is low, individual glomeruli may expand to increase the filtration area to maintain the glomerular filtration rate (GFR), leading to a state of hyperfiltration. This causes glomerular damage due to glomerular hypertension, which results in glomerular sclerosis. The glomerular count decreases further and thereby leads to a vicious cycle. Therefore, LBW infants have been suggested as having a risk of developing CKD in adulthood.6
With advancement in medical technology, more extremely low birthweight (ELBW; <1000 g) infants are surviving. The number of CKD patients whose condition is related to LBW or prematurity is also expected to increase. There is increasing evidence that some children with LBW already have decreased renal function. We reported some LBW infants who showed proteinuria and glomerular hypertrophy from childhood.8 Frankfurt et al. showed that infants with lower birthweight and gestational age had a reduced estimated GFR (eGFR) based on cystatin C (CysC) levels (CysC‐eGFR) at 3 years of age.9 Furthermore, not all LBW infants develop CKD, and certain prognostic factors are likely to affect the onset of CKD. However, no such factors have been clarified yet.
The present study aimed to investigate CysC‐eGFR in school‐age children who were ELBW infants and to determine risk factors predictive of decreased eGFR.
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