Ureteric Branching Research Articles

Robotic piver class III hysterectomy with preserving ureteral branch of uterine artery on early-stage invasive cervical cancer.

Robotic piver class III hysterectomy with preserving ureteral branch of uterine artery on early-stage invasive cervical cancer.

Surgical technique of robotic Piver class III hysterectomy with preserving ureteral branch of uterine artery on early-stage invasive cervical cancer

Surgical technique of robotic Piver class III hysterectomy with preserving ureteral branch of uterine artery on early-stage invasive cervical cancer

Embolization of pseudoaneurysms in the ureteral branch of the renal artery

BackgroundAlthough transcatheter arterial embolization for pseudoaneurysms is already well-established, ureteral artery pseudoaneurysm embolization is extremely rare. The present case shows a successful transcatheter arterial embolization for pseudoaneurysms in the ureteral branch of the renal artery due to ureteral invasion from gastric cancer.Case presentationA 57-year-old female presented with gross hematuria after treatments for poorly differentiated gastric adenocarcinoma. A contrast-enhanced computed tomography revealed pseudoaneurysms around the right ureter with a massive hematoma in the right ureter and bladder. The diagnosis was ureteral branch pseudoaneurysms resulting from possible retroperitoneal invasion due to pelvic lymph node metastasis of gastric cancer. Transcatheter arterial embolization was performed using gelatin particles, successfully controlling her hematuria without complications.ConclusionsUreteral branch artery embolization, although extremely rare, may be an effective and safe treatment option.

Horseshoe Kidney with Surplus Renal Arteries, Veins, and Roots of the Ureters

We report the anatomical findings of a kidney discovered in a 92‐year‐old male during a routine dissection of the abdominal viscera performed by medical students at the Oakland University William Beaumont School of Medicine. The lower poles of the kidney are fused together, forming an isthmus anterior to the aorta and inferior vena cava at the L3‐L4 vertebral level. The right and left kidneys ascend past the isthmus, forming a “U” shape, the defining feature of a horseshoe kidney. The left kidney stops prematurely, approximately 3.2 cm below the inferior mesenteric artery at the level of the left inferior renal artery. The right kidney drains into superior, inferior, and middle renal arteries which have three, two, and one branches respectively. Due to the size and position of the hilum, five separate roots extend outside the kidney into the right ureter. The left side is supplied by a superior and inferior renal artery, each dividing into two branches. The left inferior renal artery branches off the ventral face of the descending aorta. The left renal vein notably has three prominent tributaries from the kidney and an additional branch of the left adrenal vein. Six roots extend from the left hilum and drain into the left ureter. In total, the kidney has nine veins, six arteries, and eleven ureteric branches draining into the left and right ureters. These findings will be useful in regard to research and surgery on other horseshoe kidneys.

Current practice with grafts with multiple renal arteries in kidney transplantation: role of the methylene blue in the lower pole.

Kidneys with multiple renal arteries (MRAs) from different patches, may provide to the surgeon additional technical difficulties that make kidney transplants very challenging. MRAs have been largely debated over the years whether to be anastomosed or not due to the disappointing outcomes when it comes to inappropriate ligation or anastomosis. Some authors empirically reassure that smaller branches can be safely ligated and dissected without intraoperative and postoperative complications or compromising the functional recovery of the graft. Literature is poor about the possible differences in the management of superior and inferior polar arteries. Inferior polar arteries represent a topic of great interest as they may also supply the proximal ureter. The aim of this article is to merge the current knowledge about the management of inferior polar arteries and to highlight if there is any role of the methylene blue dye (MB) in the study of the ureteral vascularization in kidney transplantation. MB can be considered a safe and simple tool of vascular perfusion assessment in kidney transplantation. By injecting the dye-solution into the inferior MRA hidden ureteral branches can be unmasked and guide the surgeon to preserve important vessels. In view of their fundamental role in the vascularization of the ureter, the lower polar arteries of the graft, should be invariably studied by MB. It provides an objective, simple and fast tool for the evaluation of the ureteral vascularization when injected through the inferior MRA of the graft. (www.actabiomedica.it)

Structural and functional changes in the kidney caused by adverse fetal and neonatal environments

Health and disease risk in the adulthood are known to be affected by the early developmental environment. Kidney diseases are one of these diseases, and kidneys are altered both structurally and functionally by adverse pre- and perinatal events. The most known structural change is low nephron number seen in subjects born low birth weight and/or preterm. In various animal models of intrauterine growth restriction (IUGR), one of the causes of low birth weight, the mechanism of low nephron number was investigated. While apoptosis of metanephric mesenchyme has been suggested to be the cause, I showed that suppression of ureteric branching, global DNA methylation, and caspase-3 activity also contributes to the mechanism. Other structural changes caused by adverse fetal and neonatal environments include peritubular and glomerular capillary rarefaction and low podocyte endowment. These are aggravated by postnatal development of focal glomerulosclerosis and tubulointerstitial fibrosis that result from low nephron number. Functional changes can be seen in tubules, endothelium, renin-angiotensin system, sympathetic nervous system, oxidative stress, and others. As an example, I reported that aggravated nitrosative stress in a rat IUGR model resulted in more severe tubular necrosis and tubulointerstitial fibrosis after unilateral ureteral obstruction. The mechanism of various functional changes needs to be clarified but may be explained by epigenetic modifications.

Clearly imaging and quantifying the kidney in 3D

For decades, measurements of kidney microanatomy using 2-dimensional sections has provided us with a detailed knowledge of kidney morphology under physiological and pathological conditions. However, the rapid development of tissue clearing methods in recent years, in combination with the development of novel 3-dimensional imaging modalities have provided new insights into kidney structure and function. This review article describes a range of novel insights into kidney development and disease obtained recently using these new methodological approaches. For example, in the developing kidney these approaches have provided new understandings of ureteric branching morphogenesis, nephron progenitor cell proliferation and commitment, interactions between ureteric tip cells and nephron progenitor cells, and the establishment of nephron segmentation. In whole adult mouse kidneys, tissue clearing combined with light sheet microscopy can image and quantify the total number of glomeruli, a major breakthrough in the field. Similar approaches have provided new insights into the structure of the renal vasculature and innervation, tubulointerstitial remodeling, podocyte loss and hypertrophy, cyst formation, the evolution of cellular crescents, and the structure of the glomerular filtration barrier. Many more advances in the understanding of kidney biology and pathology can be expected as additional clearing and imaging techniques are developed and adopted by more investigators.

Caspase-3 regulates ureteric branching in mice via cell migration

Inhibition of caspase-3 (Casp3) reduces ureteric branching in organ culture but the mechanism remains unclear. Since Casp3 has non-apoptotic functions, we examined whether Casp3 regulates ureteric branching by promoting cell migration, using a ureteric bud (UB) cell line and Casp3-deficient (Casp3−/−) mice. Also, we examined whether Casp3 plays a role in the reduced ureteric branching of metanephroi from nutrient restricted mothers, in which Casp3 activity is suppressed. A Casp3 inhibitor Ac-DNLD-CHO reduced FGF2-induced cord formation of UB cells in 3D culture. UB cell migration assessed by Boyden chamber and wound healing assays was inhibited by Ac-DNLD-CHO. Glomerular number was reduced by ≈ 30%, and ureteric tip number was lower in Casp3−/− mice compared with controls. Maternal nutrient restriction decreased ureteric tip number in controls but not in Casp3−/−. In conclusion, Casp3 regulates ureteric branching by promoting UB cell migration. Inhibited ureteric branching by maternal nutrient restriction may be mediated by Casp3.

Comparative histological studies on the renal medulla in broiler chicken and broiler duck

Kidneys of six each of adult broiler chicken and broiler ducks were used in the present study. In the histological studies, the kidneys of all studied birds showed two zones, the cortex and medulla. The medulla occupied only a small portion of the kidney. In chicken a greater number of distinct cone-shaped medullary lobules were seen among cortical lobules while in duck they were lesser in number, more rounded in outline and were not cone shaped as in chicken. In the case of chicken more than one cortical lobule drained into a medullary lobule. Mammalian type of nephrons that occupied the juxta medullary region presented loop of Henle that was located within the medullary cone. Collecting ducts from different medullary lobules united together to form several large collecting ducts within the medulla which in turn united to form ureteral branches.

Quercetin treatment reduces the severity of renal dysplasia in a beta-catenin dependent manner.

Renal dysplasia, the major cause of childhood renal failure, is characterized by defective branching morphogenesis and nephrogenesis. Beta-catenin, a transcription factor and cell adhesion molecule, is markedly increased in the nucleus of kidney cells in human renal dysplasia and contributes to its pathogenesis by altering target genes that are essential for kidney development. Quercetin, a naturally occurring flavonoid, reduces nuclear beta-catenin levels and reduces beta-catenin transcriptional activity. In this study, we utilized wild type and dysplastic mouse kidney organ explants to determine if quercetin reduces beta-catenin activity during kidney development and whether it improves the severity of renal dysplasia. In wild type kidney explants, quercetin treatment resulted in abnormal branching morphogenesis and nephrogenesis in a dose dependent manner. In wild type embryonic kidneys, quercetin reduced nuclear beta-catenin expression and decreased expression of beta-catenin target genes Pax2, Six2, and Gdnf, which are essential for kidney development. Our RDB mouse model of renal dysplasia recapitulates the overexpression of beta-catenin and histopathological changes observed in human renal dysplasia. RDB kidneys treated with quercetin resulted in improvements in the overall histopathology, tissue organization, ureteric branching morphogenesis, and nephrogenesis. Quercetin treatment also resulted in reduced nuclear beta-catenin and reduced Pax2 expression. These improvements were associated with the proper organization of vimentin, NCAM, and E-cadherin, and a 45% increase in the number of developing and maturing nephrons. Further, our results show that in human renal dysplasia, beta-catenin, vimentin, and e-cadherin also have abnormal expression patterns. Taken together, these data demonstrate that quercetin treatment reduces nuclear beta-catenin and this is associated with improved epithelial organization of developing nephrons, resulting in increased developing nephrons and a partial rescue of renal dysplasia.

Folic acid supplementation alleviates reduced ureteric branching, nephrogenesis, and global DNA methylation induced by maternal nutrient restriction in rat embryonic kidney.

We previously reported that maternal nutrient restriction (NR) inhibited ureteric branching, metanephric growth, and nephrogenesis in the rat. Here we examined whether folic acid, a methyl-group donor, rescues the inhibition of kidney development induced by NR and whether DNA methylation is involved in it. The offspring of dams given food ad libitum (CON) and those subjected to 50% food restriction (NR) were examined. NR significantly reduced ureteric tip number at embryonic day 14, which was attenuated by folic acid supplementation to nutrient restricted dams. At embryonic day 18, glomerular number, kidney weight, and global DNA methylation were reduced by NR, and maternal folic acid supplementation again alleviated them. Among DNA methyltransferases (DNMTs), DNMT1 was strongly expressed at embryonic day 15 in CON but was reduced in NR. In organ culture, an inhibitor of DNA methylation 5-aza-2 '-deoxycytidine as well as medium lacking methyl donors folic acid, choline, and methionine, significantly decreased ureteric tip number and kidney size mimicking the effect of NR. In conclusion, global DNA methylation is necessary for normal kidney development. Folic acid supplementation to nutrient restricted dams alleviated the impaired kidney development and DNA methylation in the offspring.

Arteria renal doble en Cerdocyon thous

Objective. The aim of this study was explored the duplicity of renal artery in a specimen of Cerdocyon thous, focusing on the possibilities of clinical-surgical implication of this anatomical variation. Materials and Methods. Were dissected 32 specimens of Cerdocyon thous, obtained from the collections of the Laboratório de Ensino e Pesquisa em Morfologia dos Animais Domésticos e Selvagens do Departamento de Anatomia Animal e Humana, da Universidade Federal Rural do Rio de Janeiro e Laboratório de Anatomia Animal da Universidade Federal do Pampa. Results. Were observed a numerical variation in the left renal artery in an adult female cadaver. The left kidney had two renal arteries, one cranial and another caudal. The first renal artery of the left kidney, measuring 2.25 cm in length, originated laterally from the abdominal aorta at the level of the third lumbar vertebra. Moreover, it emanated two pre-hilar branches, one dorsal and one ventral, with the ventral branch supplying also to the adrenal gland. The second renal artery also originated laterally from the abdominal aorta at the level of the third lumbar vertebra and measured 2.36 cm in length. It also emitted two pre-hilar branches, one cranial and another caudal, which emitted the ureteral branch. Conclusions. Numerical variations of the renal arteries should be considered in the execution of surgical, radiological and experimental procedures in order to avoid mistakes made due to lack of knowledge of the possibility these variations both in domestic and wild animals.

Blood supply formation of the upper urinary tract in the prenatal period of human ontogenesis

Objective — to clarify peculiarities of blood supply of the upper urinary tract in the fetal period of human ontogenesis.Material and methods. The study was conducted on 58 specimens of human fetuses 81,0–375,0 mm of the parietal-coccygeal length (PCL) (4–10th months of the intrauterine development). A complex of morphological examinations was applied including anthropometry, morphometry, vascular injection followed by radiography and dissection, microscopy, graphic reconstruction and statistical analysis.Results. Definitive topography of the blood vessels of the upper urinary tract is established at the beginning of the fetal period. The abdominal part of the ureter is supplied by the ureteric branches of the testicular (ovarian) artery, the branches of the renal and capsular arteries. In the proximal ureter their anastomosis is determined. Variations of blood supply to the abdominal part of the ureter are arterial branches from the aorta and common glomerular arteries. At the end of the fetal period of human ontogenesis the shape of the ureter’s arteries becomes twisty that coinciding with the accelerated growth rate of their length and the slower increase of the ureter’s length. The paraureteral tissue in the surrounding layers of the retroperitoneal fascia, especially it is more prominent behind the abdominal part of the ureter, is clearly defined in the fetal period of the development. Venous outflow from the abdominal part of the ureter occurs proximally in the kidney, distally — in the ureter, capsular, testicular (ovarian) veins. An arcuate vein is clearly defined on the lateral surface of the pelvic-ureteral segment. It probably plays the role of a venous circular circle between different ways of blood outflow from the abdominal part of the ureter.Conclusions. 1. Blood supply of the abdominal segment of ureter in fetuses is ensured by the branches of the ureteral, testicular (ovarian) and renal capsular arteries. 2. The parapelvic ureteral segment is characterized by the availability of the three intraparietal venous plexuses located in the submucous, muscular and adventitial tunics anastomosing between themselves due to permeable veins. 3. A venous collector of the abdominal segment of ureter is arcuate vein located on its lateral wall. Venous outflow occurs in two directions: cranially — in the capsular and renal veins, caudal — in the capsular, ureteral and testicular (ovarian) veins. 4. 4–5 months of the development are critical periods of the abdominal ureter. This is a time for possible occurrence of congenital defect variants of blood vessels syntopia.

Intermittent Urinary Incontinence Secondary to Inverted-Y Ureteral Duplication With Perianal Ectopia

Inverted-Y ureteral duplication is one of the rarest anomalies of ureteral branching, which has been found to be more prevalent in females.2 Females commonly present with urinary incontinence often associated with distal limb ectopia to the bladder neck, uterus, or vagina.2 We present the case of a 7-year-old female with intermittent urinary incontinence who was found to have an inverted-Y ureteral duplication with perianal ectopia. We highlight the role of magnetic resonance urography in the evaluation of females with urinary incontinence and a normal renal/bladder ultrasound who are refractory to behavioral therapy.

Indocyanine Green Angiography for Preserving Ureteral Branch of Uterine Artery in Radical Hysterectomy

Indocyanine Green Angiography for Preserving Ureteral Branch of Uterine Artery in Radical Hysterectomy

Gen1 Modulates Metanephric Morphology Through Retinoic Acid Signaling.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end-stage renal disease in children. Our group has discovered that Holliday Junction resolvase gene Gen1 is a potential candidate gene for CAKUT. Gen1 mutant mice showed CAKUT phenotypes similar to those observed in retinoic acid (RA)-deficient models. The expression of Raldh2, which encodes the key enzyme in RA synthesis, was reduced in Gen1 mutant metanephros through RNA sequencing. By real-time reverse transcription-PCR, the expression of both Raldh2 and downstream Ret was reduced in embryonic day (E) 11.5 Gen1 mutant ureters and E13.5 kidneys, and expression of RA receptor alpha was decreased in E13.5 Gen1 mutant ureters and kidneys. Further studies showed that all-trans retinoic acid (ATRA) rescued solitary kidney phenotype and improved ureteric branching; ATRA should be administered after ureteric budding to avoid increasing the incidence of ectopic budding in Gen1 mutants. Luciferase intensity of RA response element was lower in CHO-K1 cells transfected with Gen1 siRNA than in those transfected with scrambled RNA, and this inhibitory effect could be reversed by ATRA. These findings indicate that Gen1 mutation can result in renal malformation through RA signaling and Gen1-loss-induced CAKUT can be partly rescued by ATRA.

Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment.

A normal endowment of nephrons in the mammalian kidney requires a balance of nephron progenitor self-renewal and differentiation throughout development. Here, we provide evidence for a novel action of ureteric branch tip-derived Wnt11 in progenitor cell organization and interactions within the nephrogenic niche, ultimately determining nephron endowment. In Wnt11 mutants, nephron progenitors dispersed from their restricted niche, intermixing with interstitial progenitors. Nephron progenitor differentiation was accelerated, kidneys were significantly smaller, and the nephron progenitor pool was prematurely exhausted, halving the final nephron count. Interestingly, RNA-seq revealed no significant differences in gene expression. Live imaging of nephron progenitors showed that in the absence of Wnt11 they lose stable attachments to the ureteric branch tips, continuously detaching and reattaching. Further, the polarized distribution of several markers within nephron progenitors is disrupted. Together these data highlight the importance of Wnt11 signaling in directing nephron progenitor behavior which determines a normal nephrogenic program.

An optimal serum-free defined condition for in vitro culture of kidney organoids

Kidney organoid is an emerging topic of importance for research in kidney development and regeneration. Conventional culture systems for kidney organoids reported thus far use culture media containing serum, which may compromise our understanding and the potential clinical applicability of the organoid system. In our present study, we tested two serum-free culture conditions and compared their suitability for the maintenance and growth of kidney organoids in culture. One of the serum-free culture conditions was the combination of keratinocytes serum free medium (KSFM) with knockout serum replacement (KSR) (KSFM + KSR), and the other was the combination of knockout DMEM/F12 (KD/F12) and KSR (KD/F12 + KSR). With cell aggregates derived from E12.5 mouse embryonic kidneys, we found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2+ nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis. With KD/F12 + KSR, we found that lower concentrations of KSR at 5–10% were superior to a higher concentration (20%) in promoting the growth of aggregates without affecting the expression levels of NPC marker genes. We also found that NPC in aggregates retained their differentiation potential to develop nephron tubules through mesenchyme-to-epithelial transition (MET), after being maintained in culture under these conditions for up to 7 days. In conclusion, we have identified a defined serum-free culture condition suitable for the maintenance and growth of kidney organoids that retain the differentiation potential to develop nephron structures. This defined serum-free culture condition may serve as a useful platform for further investigation of kidney organoids in vitro.

Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number

The regulation of final nephron number in the kidney is poorly understood. Cessation of nephron formation occurs when the self-renewing nephron progenitor population commits to differentiation. Transcription factors within this progenitor population, such as SIX2, are assumed to control expression of genes promoting self-renewal such that homozygous Six2 deletion results in premature commitment and an early halt to kidney development. In contrast, Six2 heterozygotes were assumed to be unaffected. Using quantitative morphometry, we found a paradoxical 18% increase in ureteric branching and final nephron number in Six2 heterozygotes, despite evidence for reduced levels of SIX2 protein and transcript. This was accompanied by a clear shift in nephron progenitor identity with a distinct subset of downregulated progenitor genes such as Cited1 and Meox1 while other genes were unaffected. The net result was an increase in nephron progenitor proliferation, as assessed by elevated EdU (5-ethynyl-2'-deoxyuridine) labeling, an increase in MYC protein, and transcriptional upregulation of MYC target genes. Heterozygosity for Six2 on an Fgf20-/- background resulted in premature differentiation of the progenitor population, confirming that progenitor regulation is compromised in Six2 heterozygotes. Overall, our studies reveal a unique dose response of nephron progenitors to the level of SIX2 protein in which the role of SIX2 in progenitor proliferation versus self-renewal is separable.

Endothelial marker-expressing stromal cells are critical for kidney formation.

Juvenile Flk1ST-/- kidneys displayed renal papillary hypoplasia and a paucity of collecting ducts. Twenty-four-hour urine collections revealed that postnatal Flk1ST-/- mice had urinary-concentrating defects. Thus, while lineage-tracing revealed that the renal cortical stroma gave rise to a small subset of endothelial progenitors, these Flk1-expressing stromal cells are critical for patterning the peritubular capillaries. Also, loss of Flk1 in the renal stroma leads to nonautonomous-patterning defects in ureteric lineages.