Marked interindividual variability in renal maturation of preterm infants: lessons from autopsy

Abstract

The kidney of low birthweight preterm infants is characterized by a reduced number of mature nephrons at birth. The aim of the present study was to determine whether, in preterms, active glomerulogenesis occurs in the postnatal period and whether it may compensate the reduced number of nephrons developed during the intrauterine life. Kidney samples were obtained at autopsy from 8 human fetuses, 12 premature infants, and 3 term newborns. Glomerulogenesis, as measured by radial glomerular count (RGC), was markedly decreased in all preterm infants as compared with term newborns. A marked interindividual variability was detected in the level of glomerulogenesis, which, in the vast majority of cases, did neither correlate with the gestational age at birth nor with birthweight. Active glomerulogenesis, as demonstrated by the presence of S-shaped bodies in the subcapsular region, was present in all preterm infants in the perinatal period, but it ceased in a preterm surviving for 3 months. Our data show that active glomerulogenesis continues even after birth for a short period, although it is not able to compensate a marked oligonephronia at birth. As a consequence, the incomplete nephrogenesis typical of all extremely low birthweight preterm infants possibly results in a persistent oligonephronia which should likelihood represent a major risk factors of progressive renal disease in adulthood.

Neonatal Acute Kidney Injury

“…14,15 The impact of prematurity, intrauterine growth restriction, and AKI on nephrogenesis has not been fully delineated, but small studies suggest that the extrauterine environment and AKI are detrimental to optimal nephrogenesis. [16][17][18][19] There are significant changes in neonatal renal blood flow after birth that are relevant to the study of AKI in neonates. In comparison with the 20% to 25% of cardiac output received by the adult kidney, at birth the kidneys receive 2.5% to 4.0% of the cardiac output.…”

Preterm Birth and/or Factors that Lead to Preterm Delivery: Effects on the Neonatal Kidney

“…However, in that study many of the preterm infants were also IUGR; hence, in that study interpretation of the findings is difficult, because it is well known that IUGR leads to reduced nephron endowment (see later section). Likewise, in another autopsy study the number of glomerular generations was significantly reduced in preterm kidneys compared to terms [68]. Concomitant with these studies, we have also conducted a number of studies looking at the effect of premature birth in immature preterm kidneys, both in a non-human primate model of preterm birth and in autopsied kidneys of preterm infants.…”

A spatially-averaged mathematical model of kidney branching morphogenesis

“…There is additional evidence for an impact of a variety of in utero environmental stressors on nephron number, including protein deprivation, drug and ethanol consumption and altered glucocorticoid levels (Moritz et al, 2003). Premature birth appears to accelerate the cessation of nephron formation, resulting in reduced nephron number in such individuals (Faa et al, 2010).…”

“…The final nephrons form in the immediate postnatal period, arguably in both mouse (Rumballe et al, 2011) and humans (Faa et al, 2010).…”