Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life.

Nephrogenesis occurs predominantly in late gestation at a time when preterm infants are already delivered. The aims of this study were to assess the effect of preterm birth and the effect of antenatal glucocorticoid treatment on nephrogenesis. Preterm baboons, which were delivered at 125 days gestation and ventilated for up to 21 days postnatally, were compared with gestational controls. A cohort of preterm baboons that had been exposed to antenatal glucocorticoids were compared with unexposed preterm baboons. The number of glomerular generations was estimated using a medullary ray glomerular-counting method, and glomerular number was estimated using unbiased stereology. CD31 and WT-1 localization was examined using immunohistochemistry and VEGF was localized using in situ hybridization. The number of glomerular generations was not affected by preterm birth, and total glomerular numbers were within the normal range. Kidneys were significantly enlarged in preterm baboons with a significant decrease in glomerular density (number of glomeruli per gram of kidney) in the preterm kidney compared with gestational controls. Neonates exposed to antenatal steroids had an increased kidney-to-body weight ratio and also more developed glomeruli compared with unexposed controls. Abnormal glomeruli, with a cystic Bowman's space and shrunken glomerular tuft, were often present in the superficial renal cortex of both the steroid-exposed and unexposed preterm kidneys; steroid exposure had no significant effect on the proportion of abnormal glomeruli. The proportion of abnormal glomeruli in the preterm kidneys ranged from 0.2 to 18%. In conclusion, although nephrogenesis is ongoing in the extrauterine environment, our findings demonstrate that preterm birth, independent of steroid exposure, is associated with a high proportion of abnormal glomeruli in some, but not all neonatal kidneys. Whether final nephron endowment is affected in those kidneys exhibiting a high proportion of abnormal glomeruli is yet to be confirmed.

The goal of this work was to nondestructively measure glomerular (and thereby nephron) number in the whole kidney. Variations in the number and size of glomeruli have been linked to many renal and systemic diseases. Here, we develop a robust magnetic resonance imaging (MRI) technique based on injection of cationic ferritin (CF) to produce an accurate measurement of number and size of individual glomeruli. High-field (19 Tesla) gradient-echo MR images of perfused rat kidneys after in vivo intravenous injection of CF showed specific labeling of individual glomeruli with CF throughout the kidney. We developed a three-dimensional image-processing algorithm to count every labeled glomerulus. MRI-based counts yielded 33,786 Ϯ 3,753 labeled glomeruli (n ϭ 5 kidneys). Acid maceration counting of contralateral kidneys yielded an estimate of 30,585 Ϯ 2,053 glomeruli (n ϭ 6 kidneys). Disector/fractionator stereology counting yielded an estimate of 34,963 glomeruli (n ϭ 2). MRI-based measurement of apparent glomerular volume of labeled glomeruli was 4.89 ϫ 10 Ϫ4 mm 3 (n ϭ 5) compared with the average stereological measurement of 4.99 ϫ 10 Ϫ4 mm 3 (n ϭ 2). The MRI-based technique also yielded the intrarenal distribution of apparent glomerular volume, a measurement previously unobtainable in histology. This work makes it possible to nondestructively measure whole-kidney glomerular number and apparent glomerular volumes to study susceptibility to renal diseases and opens the door to similar in vivo measurements in animals and humans. stereology; nephron; glomerulus count; nanoparticles; magnetic resonance imaging THE PURPOSE OF THIS WORK WAS to measure the number and size of all glomeruli in the entire, intact kidney using magnetic resonance imaging (MRI). Changes in the number and size of glomeruli have been linked to a number of renal and systemic diseases (5, 7). However, current techniques for counting and measuring glomeruli, such as acid maceration (4) and the dissector/fractionator stereology technique (3), require the destruction of the entire kidney. Furthermore, conventional histological techniques extrapolate the total number and size of glomeruli from a selected number of histological sections or isolated glomeruli. Current techniques are thus estimates rather than direct measurements and do not allow for localization of identified functioning glomeruli to specific parts of the kidney. A method for directly and nondestructively measuring the number and size of all glomeruli in the kidney would serve as a useful tool in animal studies and potentially in the clinic.Recently we demonstrated that intravenous injections of the iron-binding protein ferritin, functionalized with cationic amine groups (6), can be used to detect individual glomeruli both in vivo and ex vivo with MRI (1). This method is based on the electrostatic binding of cationic ferritin (CF) to the anionic macromolecules of the glomerular basement membrane (GBM) and subsequent perturbation of the magnetic field around the labeled GBM by ferritin, result...

Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension.

WE, Black MJ. Assessment of renal functional maturation and injury in preterm neonates during the first month of life.

MRI provides a new method for measuring these important microanatomical markers of disease risk and leads the way to in vivo analysis of these parameters, including longitudinal studies of animal models of CKD.

Because of the improved survival of premature neonates in recent years, it is important to investigate the effects of premature delivery on the kidney, in which nephrogenesis is still ongoing during the third trimester. Hence, an appropriate animal model that is similar to humans is essential. The aim of the current study is to determine the time course of nephrogenesis in the baboon, to establish whether it is a suitable model of human nephrogenesis. At the Southwest Foundation for Biomedical Research (San Antonio, TX), fetal baboons were delivered prematurely by cesarean delivery and at term by natural delivery. Fixed kidneys from 125-, 140-, 175-, and 185-d gestation baboons were assessed morphologically for evidence of a nephrogenic zone. Nephron number, kidney volume, and glomerular and corpuscle volume were also estimated using unbiased stereology. Morphologic assessment confirmed the presence of metanephric mesenchyme and immature glomeruli in the nephrogenic zone of the kidneys from the prematurely delivered fetuses at 125 and 140 d gestation. At 175 d gestation and at term, the nephrons seemed to be mature. Both kidney weight (R 2 ϭ 0.918, p ϭ 0.0002) and kidney volume (R 2 ϭ 0.837, p ϭ 0.001) were very strongly correlated with nephron number. There was also a direct relationship between gestational age (R 2 ϭ 0.589, p ϭ 0.03) and birth weight (R 2 ϭ 0.562, p ϭ 0.03) with nephron number. In conclusion, in this study, nephrogenesis in the baboon is complete before term by 175 d gestation, which is similar to humans. Hence, the baboon is a suitable model for future studies to investigate human kidney development. The incidence of premature delivery has increased substantially in the past decade, such that 6 -10% of all births in the Western world are premature (1). Moreover, as a result of marked advances in neonatal care, infants who are born as early as 26 wk gestation currently have an 80% chance of survival (2). Therefore, it is imperative to understand how organ development is affected in prematurely delivered individuals, especially in organs in which the ontogeny normally occurs before birth. For instance, infant respiratory distress syndrome and bronchopulmonary dysplasia are commonly observed in preterm neonates as a result of the immaturity of the lungs as pulmonary development is ongoing until term in the human (3). However, in recent years, neonatologists have been able to overcome respiratory complications to some extent by enhancing postnatal lung development, thus increasing survival of premature infants.Renal development is also rapidly occurring during the third trimester of pregnancy, and so the kidney may also be "at risk" after premature delivery. Indeed, renal failure affects~8 -24% of all preterm neonates as a result of the immature kidneys (4).Nephrogenesis, the formation of nephrons, commences at approximately the ninth week of gestation and continues until 36 wk in humans (5,6); hence, it is probable that nephrogenesis is affected in infants who are born before 36 wk gestation. Ne...

Physical inactivity is the third leading cause of the burden of disease for Australian Aboriginal adults. The neighborhood environment and social support are known to influence physical activity (PA) participation. This study examined these factors in relation to achieving PA recommendations in Aboriginal and non-Aboriginal Australians. Cross-sectional data from the 2010 Social, Economic, and Environmental Factor (SEEF) Study in New South Wales, Australia were used to estimate adjusted odds ratios (OR) for Aboriginal versus non-Aboriginal participants for PA-related attributes, including achieving PA recommendations. ORs for achieving PA recommendations were estimated in both groups. Overall, 63.1% of Aboriginal (n = 314) and 65.4% of non-Aboriginal (n = 59,175) participants met PA recommendations. Odds of healthy sleep duration were lower, and receiving GP advice to be active was higher, among Aboriginal versus non-Aboriginal participants. Aboriginal respondents had higher odds of reporting that the crime rate made it unsafe to walk and that local public transport was inaccessible. They had higher odds of disagreeing they have local shops, footpaths or free/low cost recreation facilities. PA correlates were similar in both groups. The factors relating to PA were similar in Aboriginal and non-Aboriginal people. Neighborhood and social features were less PA-favorable for Aboriginal participants suggesting multiple possible avenues for increasing PA in this older population group.