Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State.

In vascular tissue engineering strategies, the addition of vascular-specific extracellular matrix (ECM) components may better mimic the in vivo microenvironment and potentially enhance cell-matrix interactions and subsequent tissue growth. For this purpose, the exact composition of the human vascular ECM first needs to be fully characterized. Most research has focused on characterizing ECM components in mature vascular tissue; however, the developing fetal ECM matches the active environment required in vascular tissue engineering more closely. Consequently, we characterized the ECM protein composition of active (fetal) and quiescent (mature) renal arteries using a proteome analysis of decellularized tissue. The obtained human fetal renal artery ECM proteome dataset contains higher levels of 15 ECM proteins versus the mature renal artery ECM proteome, whereas 16 ECM proteins showed higher levels in the mature tissue compared to fetal. Elastic ECM proteins EMILIN1 and FBN1 are significantly enriched in fetal renal arteries and are mainly produced by cells of mesenchymal origin. We functionally tested the role of EMILIN1 and FBN1 by anchoring the ECM secreted by vascular smooth muscle cells (SMCs) to glass coverslips. This ECM layer was depleted from either EMILIN1 or FBN1 by using siRNA targeting of the SMCs. Cultured endothelial cells (ECs) on this modified ECM layer showed alterations on the transcriptome level of multiple pathways, especially the Rho GTPase controlled pathways. However, no significant alterations in adhesion, migration or proliferation were observed when ECs were cultured on EMILIN1- or FNB1-deficient ECM. To conclude, the proteome analysis identified unique ECM proteins involved in the embryonic development of renal arteries. Alterations in transcriptome levels of ECs cultured on EMILIN1- or FBN1-deficient ECM showed that these candidate proteins could affect the endothelial (regenerative) response.

Development of the renal vasculature.

The kidney vasculature has a unique and complex architecture that is central for the kidney to exert its multiple and essential physiological functions with the ultimate goal of maintaining homeostasis. An appropriate development and coordinated assembly of the different vascular cell types and their association with the corresponding nephrons is crucial for the generation of a functioning kidney. In this review we provide an overview of the renal vascular anatomy, histology, and current knowledge of the embryological origin and molecular pathways involved in its development. Understanding the cellular and molecular mechanisms involved in renal vascular development is the first step to advance the field of regenerative medicine.

The morphogenesis of the renal plexus: Renal artery and sympathetic fibers.

To examine the origin and development of the renal plexus and its relationship to the renal vessels in embryos and early human fetuses. Serial sections of 34 human embryos (stages 16 to 23 of Carnegie, 4 or 5-8 weeks) and 38 fetuses (9-19 weeks) were analyzed. Throughout the embryonic period, the kidney was not innervated by the renal plexus. Those nerves appeared at the beginning of the early fetal period (9 weeks) as branches given off by the immature autonomic abdominal plexus. The renal nerves started to approach to the kidney during the early fetal period at 9-10 weeks of development. They were distributed in close proximity to the renal arteries and their branches. They were observed first with the settlement of the renal veins. The renal artery is present as a branch of the abdominal aorta at stage 19 (between 6 and 7 weeks) prior to development of the renal plexus. The renal veins were not present during the embryonic period but appeared at the start of the fetal period, along with the renal nerves that emerged from segmented sympathetic para-aortic bodies (SPBs). Clin. Anat. 32:272-276, 2019. © 2018 Wiley Periodicals, Inc.

The Embryonic Ascent of the Kidney Revisited.

Although the embryonic kidney's ascent is well established, the intermediate morphological changes that occur during the process are unclear. To evaluate the morphological events that accompany the kidney's ascent, we examined serial sagittal sections from 24 embryos at 5-7 weeks gestation. Six specimens had bilaterally ascending kidneys that were between the levels of the second to fifth lumbar vertebrae, and each kidney had a primitive renal cortex surrounding clusters of ampullae, which branched from the pelvis, and a dense tissue band that connected the renal cortex with the embryonic adrenal cortex or celiac ganglia, and there was no adipose capsule or renal artery. The tissue band contained abundant nerve twigs from the major splanchnic nerve; thus, it was conceivable that it was sufficiently rigid to support the length of the retroperitoneal tissue mass that included the embryonic adrenal cortex, celiac ganglia, and kidney. The lumbar vertebral body's height was much shorter than that of the ascending kidney. However, the lower vertebral column's curvature was often maintained, even when the kidneys had ascended. Therefore, vertebral column straightening was not the only factor required to drive the ascent. Together with the growth of the thorax and liver, the adrenal cortex, ganglia, and kidney appeared to change simultaneously at a position relative to the vertebrae. The renal artery established a connection to the renal cortex after the ascent. Evaluations of frontal sections from five additional specimens suggested that from its initial position, the kidney extended upwards between bilateral umbilical arteries. Anat Rec, 302:278-287, 2019. © 2018 The Authors. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology published by Wiley Periodicals, Inc. on behalf of Wiley-Liss, Inc.

Spatiotemporal heterogeneity and patterning of developing renal blood vessels.

The kidney vasculature facilitates the excretion of wastes, the dissemination of hormones, and the regulation of blood chemistry. To carry out these diverse functions, the vasculature is regionalized within the kidney and along the nephron. However, when and how endothelial regionalization occurs remains unknown. Here, we examine the developing kidney vasculature to assess its 3-dimensional structure and transcriptional heterogeneity. First, we observe that endothelial cells (ECs) grow coordinately with the kidney bud as early as E10.5, and begin to show signs of specification by E13.5 when the first arteries can be identified. We then focus on how ECs pattern and remodel with respect to the developing nephron and collecting duct epithelia. ECs circumscribe nephron progenitor populations at the distal tips of the ureteric bud (UB) tree and form stereotyped cruciform structures around each tip. Beginning at the renal vesicle (RV) stage, ECs form a continuous plexus around developing nephrons. The endothelial plexus envelops and elaborates with the maturing nephron, becoming preferentially enriched along the early distal tubule. Lastly, we perform transcriptional and immunofluorescent screens to characterize spatiotemporal heterogeneity in the kidney vasculature and identify novel regionally enriched genes. A better understanding of development of the kidney vasculature will help instruct engineering of properly vascularized ex vivo kidneys and evaluate diseased kidneys.

Perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios.

PURPOSE: The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios. METHODS: A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34 + 0-36 + 6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1-8 cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups. RESULTS: Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery <37 weeks, cesarean delivery for non-reassuring fetal heart-rate testing, meconium-stained amniotic fluid, Apgar 5 min <7, transient tachypnea of the newborn, respiratory distress syndrome, neonatal intensive care unit, and hyperbilirubinemia were not statistically different between the groups (p = .054, p = .134, p = .749, p = 0.858, p = .703, p = .320, p = .185, and p = .996, respectively). Although gestational age was full-term, induction of labor rates were significantly higher in the borderline AFI group (p = .040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p = .014). CONCLUSION: Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.

The renal parenchyma-evaluation of a novel ultrasound measurement to assess fetal renal development: protocol for an observational longitudinal study.

INTRODUCTION: Disorders of fetal growth, such as intrauterine growth restriction (IUGR) and large for gestational age (LGA), have been found to have a profound effect on the development of the fetal kidney. Abnormal kidney development is associated with hypertension and chronic kidney disease later in life. This study will use a novel ultrasound measurement to assess the renal parenchymal growth and kidney arterial blood flow in the fetus to evaluate the development of the fetal kidneys and provide an indirect estimate of nephron number. Measurements in normally grown, IUGR and LGA fetuses will be compared to determine if changes in renal parenchymal growth can be detected in utero. METHODS AND ANALYSIS: This longitudinal, prospective, observational study will be conducted over 12 months in the Ultrasound Department of the Townsville Hospital, Australia. The study will compare fetal renal parenchymal thickness (RPT) and renal artery Doppler flow between IUGR fetuses and appropriately grown fetuses, and LGA fetuses and appropriately grown fetuses between 16 and 40 weeks. The fetal RPT to renal volume ratio will also be compared, and correlations between RPT, renal parenchymal echogenicity, fetal Doppler indices and amniotic fluid levels will be analysed. ETHICS AND DISSEMINATION: This study was approved by the Townsville Health District Human Research Ethics Committee. The study results will form part of a thesis and will be published in peer-reviewed journals and disseminated at international conferences.

Fetal development of the mesonephric artery in humans with reference to replacement by the adrenal and renal arteries.

According to the classical ladder theory, the mesonephric arteries (MAs) have a segmental arrangement and persist after regression of the mesonephros, with some of these vessels becoming definitive renal arteries. To avoid interruption of blood flow, such a vascular switching would require an intermediate stage in which two or more segmental MAs are connected to a definitive renal artery. To examine developmental changes, especially changes in the segmental distribution of MAs, we studied serial paraffin sections of 26 human embryos (approximately 5-7 weeks). At 5-6 weeks, 1-2 pairs of MAs ran anterolaterally or laterally within each of the lower thoracic vertebral segments, while 2-5 pairs of MAs were present in each of the lumbar vertebral segments, but they were usually asymmetrical. The initial metanephros, extending along the aorta from the first lumbar to first sacral vertebra, had no arterial supply despite the presence of multiple MAs running immediately anterior to it. Depending on increased sizes of the adrenal and metanephros, the MAs were reduced in number and restricted in levels from the twelfth thoracic to the second lumbar vertebra. The elimination of MAs first became evident at a level of the major, inferior parts of the metanephros. Therefore, a hypothetical arterial ladder was lost before development of glomeruli in the metanephros. At 7 weeks, after complete elimination of MAs, a pair of symmetrical renal arteries appeared near the superior end of the metanephros. In conclusion, the MAs appear not to persist to become a definitive renal artery.

Doppler ultrasonographic assessment of maternal and fetal arteries during normal feline gestation.

The aim of this study was to describe Doppler parameters of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries, as well as fetal heart rate (FHR), during normal feline gestation. Fifteen, 1-4 years of age, weighing 2.5-3.9kg, domestic short-hair pregnant queens, which were born in our institutional cat colony were included in this study. Color and pulsed-wave Doppler evaluations of uterine arteries were performed every 10 days (Day 0, 10, 20, 30, 40, 50, 60) from mating. Fetal Doppler and M-mode ultrasonography were performed to assess umbilical, fetal abdominal aorta, fetal renal, fetal internal carotid arteries and FHR. Both peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine artery increased up to parturition (P<0.01), while resistance index (RI) decreased from Day 10 onwards (P<0.01). From Day 40 onwards, RI of umbilical artery diminished, while PSV and EDV augmented (P<0.01). Fetal abdominal aorta (P<0.01), renal (P<0.01) and internal carotid (P<0.01) arteries diminished their RI from Days 40, 60 and 40 onwards, respectively. Both PSV and EDV of these three arteries increased progressively. Fetal heart rate was first registered on Day 20 when it began to increase up to Day 40 and then diminished to the end of gestation (P<0.01). It is concluded that blood flow of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries progressively increased during normal feline pregnancy, while FHR rose to mid gestation and then decreased up to parturition.

An unusual renal accessory artery originating from the thoracic aorta and its potential clinical implications.

UNLABELLED: We report a case of an unsual anatomical vascular blood supply to the right kidney. In an analysis of kidneys, by dissection of 39 foetuses, additional renal arteries were found in 18 cases (46.15%). In only one case (2.5%) was it noticed that the right kidney was supplied with blood by three renal arteries, one main and two additional arteries. One of the additional arteries, marked as the upper pole artery of aortic origin, separated from the thoracic aorta at the level of T11 (the eleventh thoracic rib), 1.5 cm above the truncus coeliacus. This artery, after passing through the diaphragm, entered the renal hilus at its upper part and served to vasculate that part of the kidney. CONCLUSION: The importance of this study is seen in the fact that anatomic knowledge of variations in the vascularization of the kidneys is of exceptional practical importance. Also, this information may concern transplant surgeons involved in living donor nephrectomies.

Frequency of multiple renal arteries in human fetuses.

PURPOSE: The aim of the present study was to determine the frequency of occurrence of multiple renal arteries in human fetuses. METHODS: Sixty kidneys from human fetuses (32 males and 28 females) were used, fixed and kept in 10% formol solution. The fetal age was estimated from the hallux-calcaneus length and ranged from 20 to 37 weeks of gestation, with a mean of 25.63 weeks. The renal arteries were dissected without the aid of optical instruments, and their number, length, topographical layout in relation to their origins in the aorta walls and distribution according to gender and kidney (left or right) were determined. RESULTS: Out of the 60 kidneys investigated, 78.33% had a single renal artery and 21.67% had multiple renal arteries. Most of the renal arteries emerged from the lateral wall of the aorta between the levels of the lower third of the twelfth thoracic vertebra and the upper third of the first lumbar vertebra. The length ranged from 0.15 to 1.5 cm and was slightly greater in females. CONCLUSIONS: The frequency of findings of multiple renal arteries was 21.67%.

The morphometric development and arterial vascularization of bovine fetal kidneys in the prenatal period.

This study presents a morphometric developmental analysis of bovine kidneys and a demonstration of intrarenal arterial vascularization in the prenatal period. A total of 40 Holstein bovine fetuses constituted the material of the study. The fetuses were divided into three groups, according to the gestational stages they belonged to early, mid- and late stages, such that each group comprised 10 fetuses. Sixty kidneys and their renal arteries were evaluated using morphometric measurements. Furthermore, 10 bovine fetuses were injected with cast solution to demonstrate the intrarenal arteries. Data obtained in the present study were statistically analyzed. Although the right and left kidneys did not significantly differ from each other, significant differences existed between the different gestational stages (P<0.05). The kidney parameters, including length, width and thickness, were positively correlated with both the right and left kidneys as well as with gestational age. Four types of intrarenal arterial segmentation were demonstrated. Type I was observed in 10 kidneys (50%), type II in four kidneys (20%) as well as type III, and type IV in only two kidneys (10%). In the most frequent arterial segmentation type (type I), the renal artery divided into three segmental arteries, which supplied the cranial polar, medial and caudal polar regions of the kidney, after stemming from the abdominal aorta. Furthermore, cases of double and multiple renal arteries were also observed.

Changes in central and peripheral circulation in intrauterine growth-restricted fetuses at different stages of umbilical artery flow deterioration: new fetal cardiac and brain parameters.

OBJECTIVE: To evaluate changes in central and peripheral circulation, including new and standard parameters of the fetal brain and heart in fetuses with intrauterine growth restriction (IUGR) in relation to progressive deterioration of the umbilical artery (UA). METHODS: Seventy-two IUGR fetuses were studied longitudinally. IUGR was defined as an estimated fetal weight <10th centile for gestational age. Fetuses were classified according the UA pulsatility index (PI) as: group 1, normal UA-PI (<95th centile; <1.645 z-scores), group 2, UA-PI (≥95th centile and <99th centile; ≥1.645 and <3 z-scores), group 3, UA absent end-diastolic flow, and group 4, UA reversed end-diastolic flow. Middle cerebral artery (MCA), anterior cerebral artery segments 1 (ACA1) and 2 (ACA2), aortic isthmus blood flow index (IFI), modified myocardial performance index (Mod-MPI), ductus venosus (DV), renal artery (RA), femoral artery (FA) and amniotic fluid index (AFI) were weekly evaluated until delivery. RESULTS: A total of 263 scans were performed (median, 3 (range: 1-23) per patient). There were 6 intrauterine and 2 neonatal deaths. Although all cerebral arteries showed a reduction in the PI, ACA1 showed the earliest vasodilatation. From group 2 onwards, all cerebral vessels had a similar pattern of vasodilatation. Mod-MPI became abnormal at group 1 with no further changes. IFI and DV became constantly abnormal starting from group 2. No changes in the RA-PI or FA-PI were documented. CONCLUSION: The process of hemodynamic deterioration in IUGR fetuses seems to be earlier represented by the ACA1 and the Mod-MPI. Signs of further deterioration were observed in the DV, IFI and MCA. The peripheral blood in the RA and FA did not show any change. AFI showed a late deterioration process.

Renal artery variations: embryological basis and surgical correlation.

Understanding anatomy of the vascular variations of kidney is essential for the clinician to perform procedures such as renal transplantation, interventional radiological procedures and renal vascular operations more safely and efficiently. In order to facilitate the clinical approaches, we studied renal arterial pattern in 50 formalin-fixed cadavers, on 100 kidneys. We observed prehilar multiple branching patterns in 11 (11.66%) cases, duplication of renal artery in eight (8.33%) cases and superior polar artery in seven (6.66%) cases. In the present study findings discussed with its clinical correlation.

Suprarenal gland-arterial supply: an embryological basis and applied importance.

Variation arterial anatomy of suprarenal gland is significant for radiological and surgical interventions. Knowledge of anomalous suprarenal artery is required to avoid complications in surgical procedure. Arterial architecture of human suprarenal gland was studied in sixty-eight cadavers of adult male and female. In all cases, superior suprarenal artery on right side was normal in origin but on left side, 24% showed anomalous origin. The incidence of anomalous origin of middle suprarenal artery on right side was 47% and on left side 6%. Anomalous origin of inferior suprarenal artery on the right side was 29% and left side 35%. The superior suprarenal artery was present in all subjects. However, there was absence of right middle suprarenal artery in 29% and left inferior suprarenal artery in 35% subjects. The most variable group was inferior suprarenal artery. The study result is being described to report anomalous origin of suprarenal arteries in the light of surgical, radiological and embryological significances. Present study findings suggest, thorough knowledge of anomalous arterial anatomy of suprarenal gland is required for surgical and radiological interventions of retroperitoneal organs of upper abdomen to avoid complications.

Variations of the origin of renal arteries in the fetus identified on power Doppler and 3D sonography.

PURPOSE: To investigate anatomic variations of renal arteries (RAs) using 2-dimensional (2D)/3D power Doppler sonography (PDUS) in normal fetuses and in fetuses with renal anomalies. METHODS: The origin, direction, and distribution of RAs were studied in 120 fetuses without renal malformations using 2D/3D PDUS. Studies were performed between 14 and 17 weeks of gestation age on 64 male and 56 female fetuses. PDUS of the RAs was also performed in 12 fetuses with renal anomalies. RESULTS: In 117/120 fetuses, a single RA was found to originate from each side of the abdominal aorta. The origin of the right RA from the abdominal aorta was superior to, at the same level as, and inferior to that of the left RA in 47% (55/117), 25.5% (30/117), and 27.5% (32/117) of the cases, respectively. An accessory right RA was found in 3 cases. Bifurcation of the right RA was found in 2 cases. There were no variations of the origin of renal vessels in 69% of the cases (83/120), whereas the remaining 31% (37/120) had 1 or several variation patterns. Variations in renal vessels were found in 8 of the 12 fetuses with renal malformations: accessory artery in 3 cases, origin of the right RA from the iliac artery in horseshoe kidney and in 2 cases with pelvic kidney, and bifurcation in 2 of the fetuses with double collecting system. CONCLUSIONS: Variations in origin and distribution of fetal RAs are frequently observed in normal pregnancies. The majority of renal malformations are associated with such vascular variations.

Dual segmental arterial supply to a single renal lobule: a study using semi-serial sections of mid-term fetuses.

OBJECTIVE: To determine which and how many segmental arteries supply a single renal lobule especially at and near the segmental border, as no data are available on the arterial supply to a single renal lobule (a pyramid and its covering cortex) at the border between renal segments. MATERIALS AND METHODS: We studied semi-serial sections (100 microm intervals; haematoxylin and eosin staining) of 26 kidneys obtained from 13 mid-term human fetuses (20-30 weeks gestation). Eleven fetuses were used for horizontal sections and two for sagittal sections. Section to section, we first traced the renal pyramids using a pen to understand the lobular configuration. RESULTS: Fusion of the medullary pyramids was usually evident along the segmental borders, except for the border between the upper and middle segments. This fusion often accompanied a pair of arcuate arteries, each of which arose from a different renal segment, but shared a common corticomedullary junction to supply a single lobule. The incidence of fusion was high along the anterior border of the posterior segment as well as the border between the apical and upper segments. When the lower segmental artery entered the parenchyma distant from the renal hilus, fusion of pyramids occurred along the border between the posterior and lower segments in association with double arcuate arteries. CONCLUSIONS: A single lobule is most likely to be shared by double segments at or near the segmental border. This morphology seems to be a result of lobule fusion during development and growth. Thus, in adults, a dual segmental supply to a single lobule seems to be more frequent than in fetuses.

[Evaluation of blood flow in the fetal renal artery between the 22nd and 38th week in normal pregnancies]. / Avaliação do fluxo na artéria renal fetal entre a 22a feminine e a 38a feminine semana em gestações normais.

PURPOSE: to describe values found for the resistance index (RI), pulsatility index (PI) and the systole/diastole (S/D) ratio of fetal renal arteries in non-complicated gestations between the 22nd and the 38th week, and to evaluate whether those values vary along that period. METHODS: observational study, where 45 fetuses from non-complicated gestations have been evaluated in the 22nd, 26th, 30th and 38th weeks of gestational age. Doppler ultrasonography has been performed by the same observer, using a device with 4 to 7 MHz transducer. For the acquisition of the renal arteries velocity record, a 1 mm to 2 mm probe has been placed in the mean third of the renal artery for the evaluation through pulsed Doppler ultrasonography. The measurement of RI, PI and S/D ratio from three consecutive waves was performed with the automatic mode. To detect significant differences in the indexes' values along gestation, we have compared values obtained at the different gestational ages, through repeated measures ANOVA, followed by Tukey's post-hoc test. RESULTS: There were no significant differences between the right and left renal arteries, when the RI, IP and S/D ratio were compared. Nevertheless, a change in the values of these parameters has been observed between the 22nd week (RI=0.9 +/- 0.02; PI=2.4 +/- 0.02; S/D ratio=11.6 +/- 2.2; mean +/- standard deviation of the combined mean values of the right and left renal artery) and the 38th week (RI=0.8 +/- 0.03; PI=2.1 +/- 0.2; S/D ratio=8.7 +/- 2.3) of gestation. CONCLUSIONS: the parameters evaluated (RI, PI and S/D ratio) have presented decreasing values between the 22nd and 38th, with no difference between the fetus's right and left sides.

Multiple anomalies involving testicular and suprarenal arteries: embryological basis and clinical significance.

Variations in the origin of arteries in the abdomen are very common but with the invention of new operative techniques within the abdominal cavity, the anatomy of abdominal vessels has assumed much more clinical importance. During routine dissection of the abdominal cavity, we came across multiple arterial anomalies involving testicular and suprarenal arteries. On the right side, there was double testicular artery (medial and lateral) and the right inferior suprarenal artery aroused from the medial testicular artery. The right inferior phrenic artery (IPA) and middle suprarenal artery took origin from a common trunk just above the origin of right renal artery (RRA). On the left side, the left testicular artery was arching over the lower tributary of the left renal vein proper (LRVP). Apart from the developmental and morphological interest in arching gonadal arteries, they are of practical importance from a clinical and surgical viewpoint. The embryological and clinical significance of above variations has been described.