Growth and development of the human fetal kidney

Growth and development of human fetal kidney was studied with respect to anthropometric measurements, histological appearance and certain functional parameters. Upto 30 weeks of gestational age there was a proportional growth of the kidneys in respect of gestational age. The formation of the glomerular capsule was by a process of sequential development of the endo and epithelial cells rather than by an invaginative process. There comes a time in the development of the kidney when the developing nephrons appear to lie in pools of blood. Glomerular filtration appears earlier than tubular reabsorption. The process of tubular secretion was found to be associated with induction of specific proteins.     

Maternal protein restriction that does not have an influence on the birthweight of the offspring induces morphological changes in kidneys reminiscent of phenotypes exhibited by intrauterine growth retardation rats

Severe restriction of maternal protein intake to 6–8% protein diet results in intrauterine growth retardation (IUGR), low birthweight and high risk of metabolic syndrome in the adult life of the offspring. However, little information is available on the effects of maternal protein restriction on offspring under the conditions that does not have an influence on their birthweight of the offspring,. In the present study, pregnant rats were kept on a diet consisting of either 9% (low‐protein, Lp rats) or 18% (normal‐protein, Np rats) protein by weight/volume/etc. After birth, both Lp and Np rats were kept on a diet containing 18% protein. Neonatal body weight was significantly lower in Lp rats compared to Np rats from 4 days to 5weeks after birth. While glomerular number per unit volume (1 mm³) of the kidney (Nv) was comparable between Lp and Np rats 4 weeks after birth, the Nv was significantly decreased in Lp rats at 20 weeks after birth. Four and 20 weeks after birth, glomerular sclerosis index, interstitial fibrosis score, and ratio of ED1‐positive cell ratio were all significantly higher in Lp compared to Np rats. Transforming growth factor‐β1‐positive cells were observed in the distal tubules in the kidney of 4‐ and 20‐week‐old Lp rats kidneys, but not in those of age‐matched Np rats. Altogether, these findings revealed that maternal protein restriction that does not have an influence on the birthweight of the offspring, induces similar changes as those seen in the kidneys of IUGR neonates.     

肿瘤坏死因子-α在宫内急性缺氧缺血后胎鼠肾脏炎性反应发生中的作用

目的：探讨宫内急性缺氧缺血后肿瘤坏死因子α（TNF－α）在胎鼠肾脏炎性反应发生中的作用。方法：通过钳夹孕21日龄大鼠供应子宫的血管，制备胎鼠宫内不同程度缺氧缺血（HI）模型和再灌注不同时间模型；利用酶联免疫分析方法和化学方法测定胎肾组织匀浆中TNF－α和髓过氧化物酶（MPO）的变化；同时观察肾组织形态学改变。结果：1．宫内HI后胎肾TNF－α水平上升，在缺血35－45min时明显（P＜0．05），缺血15min后再灌注1h胎肾TNF－α水平即开始显著升高（P＜0．01），8h达高峰，30h接近假手术组。2．胎肾MPO活力随缺血程度加重而略渐升高，缺血45min时明显（P＜0．05），缺血15min再灌注4h时胎肾TNF－α水平即明显升高（P＜0．05），15h达高峰（P＜0．01），30h仍高于假手术组（P＜0．05），3．组织学改变，缺血15min再灌注15h病理改变最明显，肾组织普遍充血和渗出，可见中性粒细胞浸润，肾小管普遍空泡变性，伴细胞核模糊，细胞崩解，基底膜阶段性断裂，尤以近端小管明显。结论：宫内急性缺血和再灌注后胎肾存在炎症反应，TNF－α可能是启动该反应的重要媒介，而MPO可反映炎症反应程序。αα     

Effects of maternal uninephrectomy on the development of fetal rat kidney with special reference to the proliferative activity and epidermal growth factor (EGF).

ABSTRACT Immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and EGF receptor (EGFR) in the kidney of fetal rats from uninephrectomized mothers were examined. As the index of proliferative activity, PCNA positive cell ratios in glomeruli and proximal tubules were determined. In the fetuses from uninephrectomized mothers and sham-operated mothers, the PCNA positive cells were seen predominantly in the nephrogenic zone of the kidney. On fetal day 22, the PCNA positive cell ratio in the glomerulus of the fetus from uninephrectomized mothers (E fetus) was significantly lower than that in the glomerulus of the fetus from sham-operated ones (C fetus). The proximal tubular cells showed positive reaction to EGF and EGFR antibodies in both fetuses. On fetal day 22, the reactions of the proximal tubules to EGF and EGFR antibodies were stronger in E fetus than in C fetus.
These results indicate that maternal uninephrectomy causes decreased proliferative activity of the glomerulus and increased reactions of the proximal tubules to EGF and EGFR antibodies in fetal rat kidney, suggesting accelerated development of the kidney.     

Insulin deficiency: Effects on fetal growth and development

Insulin deficiency in either the mother or foetus has significant effects on fetal growth and development. In the human, maternal insulin deficiency, or diabetes mellitus, leads to macrosomia and increased adiposity of the foetus, while specific fetal hypo-insulinaemia is associated with intra-uterine growth retardation. When maternal diabetes is induced in experimental animals, no consistent increases in fetal bodyweight are observed although the body fat content of the foetus is increased in the majority of species studied. The magnitude of the fetal weight gain during maternal diabetes appears to be determined by the body fat content of the foetus, the severity and duration of the diabetes and by the temporal pattern of maternal hyperglycaemia observed during pregnancy. The latter factors, in particular, influence the level of insulin in the foetus which, in turn, regulates the rate of intra-uterine growth. By contrast, fetal insulin deficiency has a more uniform effect on fetal growth and leads to impaired growth in both experimental and naturally occurring hypo-insulinaemic conditions. Fetal insulin deficiency reduces fetal growth by decreasing nutrient uptake and utilization of the fetal tissues and by altering the circulating concentrations of the insulin-like growth factors. Consequently, deficiencies in either fetal or maternal insulin secretion during pregnancy can alter fetal growth and have important consequences for perinatal survival and postnatal morbidity.     

Becoming unique: A qualitative study of identity development of adolescent kidney recipients

Teenagers who receive a renal organ transplant have to take up the double challenge of identity development, the primary task of adolescence, and of overcoming the complexities of their illness. Previous qualitative studies found that adolescents felt that the organ transplant and its treatments mainly defined who they are. The relationship to the donor can be a source of concern for some of them, especially for those who received from a parent and feel an obligation to be obedient and grateful. While donor parents are known to interpret their gesture as giving life for a second time, no research to date has described how this particular gesture may influence adolescent development. The present article aims to examine and describe identity development of teenage kidney recipients in a context of parental or deceased donation. We used a qualitative design involving individual interviews with 10 adolescents. Five of them received from a donor parent, five from a deceased donor. Data were analyzed using IPA. Results suggest that identity development is influenced by similar concerns for all adolescents regardless of donor source: body image, social relationships, and anxiety about the future. One aspect that stood out from the discourse of those who received from a parent was feelings of guilt towards the donor when engaging in behaviors that could comprise graft survival, which was a challenge for identity development. Receiving the transplant freed teens from the struggle of just managing their illness and was a catalyst for exploration and engagement, which are crucial for identity development.     

Effects of maternal depression on cognitive development of children over the first 7 years of life

The effects of postnatal depression on cognitive test scores at 20 months and 4; 8 years of age as well as the timing (onset in the early postnatal period versus later), severity, number of episodes, duration of longest phase, recency, and chronicity of material depression on children's cognitive scores at 6; 3 years was investigated. In South Bavaria, Germany, 1,329 mothers of singletons were screened when the children were 6; 3 years of age for the presence of depressive symptoms since the birth of their infant. A standard interview (SADS-L) was used to ascertain DSM-IV diagnosis and details of depressive episodes. Ninety-two mothers were diagnosed as having suffered DSM-IV defined depression (7%). Seven hundred and twenty-one mothers had no depressive episodes or symptoms from their children's birth until 6; 3 years and were used as control group. The children had been assessed with the Griffiths Scales of Babies' Abilities (20 months), the Columbia Mental Maturity Scales (CMM) at 4; 8 years, and the Kaufman Assessment Battery for Children (K-ABC) at 6; 3 years. No significant main effects of severity, timing of onset, duration, or chronicity of depression of the child's cognitive development were found. Significant interactions of gender with chronicity of maternal depression (i.e. early-onset major and repeated episodes) were detected. Low SES boys or boys born at neonatal risk of mothers with chronic depression had lower Achievement Scores in the K-ABC at 6; 3 years than children of mothers with less severe depression or controls. It is concluded that maternal depression per se has negligible effects on children's cognitive development. Long-term effects may be found when maternal depression is chronic, the child is a boy and neonatal risk-born, or the family suffers other social risks.     

Impact of laparoscopic donor nephrectomy on allograft function in pediatric renal transplant recipients: a single-center report

Laparoscopic donor nephrectomy (LDN) is rapidly becoming the preferred technique for the procurement of living donor kidneys. An association of this technique with delayed graft function and higher risk for rejection has been reported in pediatric recipients. We reviewed our experience of 17 pediatric patients who received a living donor kidney, from 2002 to 2004, procured by LDN, and compared it with a matched group that received living donor kidneys harvested by the open technique. Patient demographics, etiology of renal failure, intra-operative events, length of stay, serum creatinine decline, and graft function were reviewed. Our experience confirmed the findings of earlier reports specifically in small pediatric recipients. The LDN group showed a significantly slower decline in creatinine in the immediate post-operative period and longer intra-operative time. However, there was no difference between the two groups in the length of hospital stay, and creatinine clearances at discharge, six, 12 and 24 months post-operatively. The incidence of acute rejection was similar in both groups. LDN is a safe procurement modality for pediatric patients. The risk for prolonged OR time and delay graft function has to be considered during the evaluation process.     

The timing of maternal depressive symptoms and child cognitive development: a longitudinal study

Background: Maternal depression is known to be associated with impairments in child cognitive development, although the effect of timing of exposure to maternal depression is unclear. Methods: Data collected for the Avon Longitudinal Study of Parents and Children, a longitudinal study beginning in pregnancy, included self‐report measures of maternal depression the Edinburgh Postnatal Depression Scale, completed on 6 occasions up to 3 years of age, and IQ of the index child (WISC) measured at aged 8 years. We used these data to assign women to 8 groups according to whether depression occurred in the antenatal, postnatal, preschool period, any combination of these times, or not at all. We compared a model comprising all patterns of depression (saturated model) with models nested within this to test whether there is a relationship between depression and child cognitive development and, if so, whether there is a sensitive period. We then investigated the relationship with child IQ for each model, following adjustment for confounders. Results: Six thousand seven hundred and thirty‐five of 13,615 children from singleton births (49.5%, of eligible core sample) attended a research clinic at 8 years and completed a WISC with a score ≥ 70. A total of 5,029 mothers of these children had completed mood assessments over the 3 time periods. In unadjusted analyses, all three sensitive period models were as good as the saturated model, as was an accumulation model. Of the sensitive period models, only that for antenatal exposure was a consistently better fit than the accumulation model. After multiple imputation for missing data (to n = 6,735), there was no effect of postnatal depression on child IQ independent of depression at other times [?0.19 IQ points, 95% confidence interval (CI) ?1.5 to 1.1 points]. There was an effect of antenatal depression (?3.19 IQ points, 95% CI: ?4.33 to ?2.06) which attenuated following adjustment (?0.64 IQ points, 95% CI: ?1.68 to 0.40). Conclusions: The postnatal period is not a sensitive one for the effect of maternal depression on child cognitive development.     

Structural maturation of the human fetal lung: a morphometric study of the development of air-blood barriers

To quantitatively follow the progressive capillarization of the fetal airway epithelium, we examined human lung tissue from nine fetuses ranging in gestational age from 18-26 wk. Our goals were to 1) determine the initial time of appearance of the air blood barrier (ABB) in the fetus; 2) follow the increase in the number of ABB per total epithelial airway surface (capillary load) with gestational age; and 3) measure the thickness of the ABB. Our results, obtained by using light and electron microscopy and an interactive computerized morphometry system, show that ABB first appear at 19 wk. Increasing gestation is accompanied by an exponential increase in the number of ABB (r = 0.96) and the total surface area that the ABB contribute to the total surface area of airway epithelium (r = 0.93). ABB thickness is comparable to the dimensions of minimal barrier thickness of the adult ABB. The structural development that we describe may be one of the factors determining preterm viability.     

Perinatal development of the rat hip joint with restrained fetal movement

ABSTRACT  We compared the structures of the femoral head (FH) of neonates between normal and operated legs with restrained fetal movement using an exo utero technique. At embryonic day (E) 16.5, one hind limb was sutured onto the embryonic membrane and the fetuses were allowed to develop exo utero until the term (E22.5). There was no significant difference in the largest diameter of the FH between the non-operated and operated side FH in the operated neonates and the FH of the non-operated neonates. By scanning electron microscopy, roughness and collagen fiber bundles, which were detected on the surface of the operated side FH at E18.5, disappeared at E22.5. However, the operated side FH was deformed and the surface cell arrangement was more irregular than that of the controls at E22.5 by light microscopy. These results suggest that the abnormality of cell arrangement caused by the restraint of fetal movement may induce the deformity and irregularity of the FH surface, although this operation may not disturb the basic cellular activities such as cell proliferation as well as the secretion of cartilage matrix and collagen fibers. To further investigate the recovery process in the operated newborns after releasing the restraint, we bred them artificially for a considerable period after birth. The operated side FH surface of the neonate bred for 45 hours was smoother than that at E22.5 and similar to that of the non-operated side FH. This result suggests that the proper movement of the extremities after birth may recover the deformity caused by restrained fetal joint movement     

Epidemiological appraisal of the literature on the fetal alcohol syndrome in humans

An evaluation of the evidence regarding the association between heavy maternal alcohol intake during pregnancy and the occurrence in offspring of that cluster of abnormalities called the Fetal Alcohol Syndrome is undertaken from an epidemiological perspective. Areas of concern in assessing the literature include the objectivity with which the maternal drinking history was obtained, the nature, systematic or not, of examination of offspring, the presence or absence of a comparison group, the control for potentially confounding factors and, perhaps most important of all, whether or not the identification of a case was made blind to knowledge of the maternal drinking history. While well-documented evidence that can implicate a hypothesized teratogen is difficult to obtain, the data available concerning the effects of in utero exposure to high doses of alcohol must be carefully and thoughtfully scrutinized so that valid inferences may be drawn. In this review particular attention is focused on the nature of the association between in utero alcohol exposure and mental retardation, certainly the most devastating of the FAS features.     

Multicystic kidney dysplasia: a prospective study on the natural history of the affected and the contralateral kidney

In a 6-year period, 41 young infants with multicystic kidney dysplasia were seen in our department. In 30 cases, the diagnosis had already been suspected by prenatal ultrasonography. A prospective protocol was proposed to the parents which comprised ultrasound evaluation every 3 months until the age of 24 months and renal function assessment at the age of 18 months. In 33 patients, the study was completed as scheduled. At the start of the study, the maximal diameter of the multicystic kidney was above the mean length of normal kidneys in all cases where precise measurement was possible. Within 24 months, 7 of the dysplastic kidneys disappeared, 20 regressed in size, 1 remained unchanged and only 5 increased in size. Between the age of 0 to 3 months, renal length of the contralateral kidney was within the normal range in 19 infants and above +2SD in 14 cases. At the age of 18 to 24 months, renal length was, with few exceptions, between 0 and +4SD. Inulin clearance was normal in all 33 individuals with a median value of 112 ml/min per 1.73 m². Conclusion As a rule, multicystic kidneys shrink in the first 2 years of life. In most cases the contralateral kidney maintains a normal renal function as a consequence of progressive compensatory hypertrophy. Received: 19 November 1997 / Accepted in revised form: 31 January 1998     

Prenatal developmental effects of pure 2,4-dichlorophe-noxyacetic acid (2,4-D) on the rat

ABSTRACT 2,4-Dichlorophenoxyacetic acid (2,4-D) a plant growth regulator, has been used worldwide as an herbicide. The phenoxyacetic acid herbicides contain both 2,4-D and 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) along with emulsifiers, solvents and contaminants; these have been recognized as teratogen in the rat and mouse. Although the high teratogenicity of phenoxyacetic herbicides has been attributed to the 2,4,5-T and the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the possibility that 2,4-D might play a role has not been clearly ruled out We designed this study to evaluate the effects of pure 2,4-D, and herein describe the precise fetal visceral malformations. We randomly distributed pregnant Wistar rats in to three main groups according to organogenesis during which pure 2,4-D was administered at different doses: l)-over all organogenesis (gestational days 6 to 15), 2)-early organogenesis (gestational days 6 to 10), and 3)-late organogenesis (gestational days 11 to 15). We found that the pure 2,4-D is maternally toxic and has a dose-related embryolethality. The visceral malformations induced in the fetuses included ureteric dilatations and hydronephrosis, as reported, in conjunction with the herbicide forms. In addition, we observed an association with renal and urogenital aplasia, which were observed in the early organogenesis period. We performed a histopatho-logical examination and discussed the mechanism of the pathological processes. We conclude that the pure 2,4-D itself is maternally toxic and embryolethal, and potential inducer of kidney and urogenital malformations in the rat. The types of kidney and urogenital malformations seen indicated that the 2,4-D interferes in the early developmental stage of the urogenital system.     

Effects of lactational cyclosporine A use on rat pups

Abstract:  We aimed to evaluate the structural and functional changes in the thymus and kidneys of rat pups whose mothers were given cyclosporine A (CsA) during lactational period. Six adult nursing Wistar rats and their 30 pups were studied. Rat pups were divided into four groups as follows: 21-day treated group and 21-day placebo group, each including 10 breastfeeding pups sacrificed on the 21st day, whose mothers were given CsA or placebo, respectively ( infancy groups ) and, 60-day treated group and 60-day placebo group, each including five breastfeeding pups sacrificed on the 60th day, whose mothers were given CsA or placebo, respectively ( puberty groups ). While CsA levels of mother rats were very high, CsA levels of 21-day treated group pups were zero. There were no renal histomorphometric differences between study and control pups in both age groups. Renal function parameters showed significant differences between study and control pups in the infancy group: the 21-day treated group pups had significantly lower urine volume, proteinuria, FE_Na and urinary NAG/creatinine ratio. GFR was also lower in the 21-day treated group, but the difference was not significant, and serum creatinine levels were also not different. Renal function differences were not present among the pubertal pups. Thymic corticomedullary ratio of the 21-day treated group was significantly higher than the 21-day placebo group, while there was no difference between the 60-day treated group and 60-day placebo group. There were no significant changes in the number and distribution of CD3+, CD4+, and CD8+ thymocytes between study and control pups in both age groups. In conclusion, breastfeeding by CsA-treated mother rats induced structural alterations in the thymus and functional changes in the kidneys of the rat pups during infancy. Disturbances in the kidneys and thymus mostly improved after CsA exposure was over.     

Effects of cyclosporin A on fetal development in the rat

The fetotoxicity of cyclosporin A (CsA) was examined in multiparous Sprague-Dawley rats given the drug (25 mg/kg/day) during different phases of gestation, the effects on the outcome of pregnancy being ascertained on day 19. CsA given from days 1 to 7 caused a small but significant reduction in litter size, with no significant increase in the number of resorptions. When the drug was administered from day 8 to 14 there was no significant change in litter size, but a very striking increase in the incidence of resorptions. This fetotoxic effect was also evident but less marked when the drug was withheld until day 15. Reduction in fetal weight was only present in the group given CsA from days 8 to 14. In surviving fetuses the presence of focal decidual necrosis was more frequent in mothers receiving CsA, suggesting a possible mechanism whereby CsA may mediate its fetotoxic effects.     

Maternal and fetal circulation of unusual bile acids: A pilot study

Background: Large amounts of unusual bile acids are synthesized by the fetal liver in late gestation. These compounds are mostly transferred from fetus to mother, although some are excreted into the amniotic fluid. We investigated the role of placental transfer of bile acids in fetal bile acid metabolism, particularly with respect to the unusual bile acids (1β‐hydroxylated and ketonic bile acids). Methods: We measured concentrations of bile acids in umbilical cord blood and urine of newborn infants, and in perinatal maternal serum and urine, using gas chromatography‐mass spectrometry. Serum and urine specimens from healthy non‐pregnant women were used as controls. Results: In newborn infants at delivery, cord blood and urine contained mostly primary and 1β‐hydroxylated bile acids, respectively. We also detected large amounts of ketonic bile acids in their urine, and the urinary concentration of total bile acids was elevated. Main maternal bile acids at 30 and 35 weeks of gestation and at delivery were 1β‐hydroxylated bile acids. After delivery, main bile acids changed from 1β‐hydroxylated bile acids to primary bile acids (P < 0.03), which also predominated in healthy non‐pregnant women. Conclusion: Fetally synthesized unusual bile acids were transported from fetus to mother. Pregnant women appear to excrete these bile acids into the urine, lowering both fetal and maternal serum bile acid concentrations.