Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants

Abstract

Until now oligonephropathy to indicate "too few nephrons" has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight < or = 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < or = 40 days vs. long survival > or = 40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with "basophilic S-shaped bodies" was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving > or =40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman's capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.

Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease

“…Indeed, extrauterine growth restriction was associated with significantly lower GFRs in VLBW children at a mean of 7.6 years of age, and conversely the odds of renal impairment was 33% lower at 6.4 years among VLBW children who had gained more weight in neonatal intensive care, demonstrating the importance of early nutrition on kidney development 41,42 . Nephron number was found to be lower in premature infants who developed renal failure before death, although whether this was a cause or consequence of low nephron number is unknown 40 .…”

“…Nephron number correlates with gestational age in premature infants in whom nephrogenesis may continue for a period after birth, although glomeruli are large and abnormal and renal maturation appears accelerated 16,40 . Consistent with these morphologic abnormalities, prematurity is a risk factor for acute kidney injury (AKI), which is an independent predictor of mortality and subsequent CKD in very low birth weight (VLBW) infants 12 .…”

“…Post-natal factors: Nephrogenesis in humans is complete at term, however ongoing nephrogenesis has been observed up to 40 days after birth in infants born before 30 weeks of gestation 40 . A window of vulnerability therefore exists in preterm infants in which kidney development can be impacted (Table 1).…”

“…As discussed above, especially in premature and LBW infants, post-natal malnutrition and clinical circumstances may impact nephrogenesis, childhood renal function and longterm renal disease risk (Figure 1) 12,40,42 . In LBW rats, low nephron numbers were restored to normal, and the development of hypertension abrogated by provision of adequate post-natal nutrition 58 .…”

Strategies to improve the understanding of long-term renal consequences after neonatal acute kidney injury

“…Infants born at <34 wk of gestational age may have a paucity of nephrons (10). If nephrogenesis is continuing after birth, the extrauterine environment may not allow for proper glomerular development (11). Thus, premature infants <34 wk are at risk for CKD due to lesser number of nephron.…”