Renal System Development

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Introduction

Gray1127.jpg

The paired adult kidneys consist of a functional unit called the "nephron", that filters blood, excretes waste, reabsorbs water (and other compounds) and has endocrine functions. Each adult human kidney typically contains about 750,000 nephrons, though the total number can vary significantly from as few as 250,000 to as many as 2,000,000.[1][2]

In the embryo, nephron development, nephrogenesis, occurs through several stages involving classical epithelial/mesenchyme type of interactions. Nephrogenesis continues into the late fetal period (GA week 34–35) and while the fetal kidney does produce urine, not until after birth does the glomerular filtration rate (GFR) increases rapidly due to a postnatal drop in kidney vascular resistance and an increase in renal blood flow.

The urinary system is developmentally and anatomically associated with genital development, often described as the "urogenital system". (More? Genital System Development)


Renal Links: Introduction | Lecture - Renal | Lecture Movie | Urinary Bladder | Stage 13 | Stage 22 | Fetal | Renal Movies | Stage 22 Movie | Histology | Abnormalities | Molecular | Category:Renal
Historic Embryology - Renal  
1907 Urogenital images | 1911 Cloaca | 1921 Urogenital Development | 1915 Renal Artery | 1917 Urogenital System | 1925 Horseshoe Kidney | 1926 Embryo 22 Somites | 1930 Mesonephros 10 to 12 weeks | 1931 Horseshoe Kidney | 1932 Renal Absence | 1939 Ureteric Bud Agenesis | 1943 Renal Position

Some Recent Findings

Cloacal septation model[3]
Renal Nephron
  • Histone deacetylase 1 and 2 regulate Wnt and p53 pathways in the ureteric bud epithelium[4] "Histone deacetylases (HDACs) regulate a broad range of biological processes through removal of acetyl groups from histones as well as non-histone proteins. Our previous studies showed that Hdac1 and Hdac2 are bound to promoters of key renal developmental regulators and that HDAC activity is required for embryonic kidney gene expression. However, the existence of many HDAC isoforms in embryonic kidneys raises questions concerning the possible specificity or redundancy of their functions. We report here that targeted deletion of both the Hdac1 and Hdac2 genes from the ureteric bud (UB) cell lineage of mice causes bilateral renal hypodysplasia. One copy of either Hdac1 or Hdac2 is sufficient to sustain normal renal development."
  • Bmp7 functions via a polarity mechanism to promote cloacal septation[5] "During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood. ...Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations."
  • Size and location of the kidneys during the fetal period[6] "The level of the left kidney was higher than the level of the right kidney in the fetal period. The posterior surface relations to the ribs showed certain ascendance during gestation, corresponding to vertebral levels. However, fetal kidneys do not reach the same level as adults at full term. The kidneys move farther apart from the midline of the body during the fetal period. The dimensions, weight, and volume of the kidneys increased with gestational age during the fetal period. The ratio between kidney weights and fetal body weights were determined, and we observed that the ratio decreased during the fetal period. There were no sex or laterality differences in any parameter." (See also Fetal Development)
  • Characterization of Mesonephric Development and Regeneration Using Transgenic Zebrafish. [7] "The majority of previous studies have focused on the pronephros of zebrafish, which consists of only two nephrons and is structurally simpler than the mesonephros of adult fish and the metanephros of mammals. To evaluate the zebrafish system for more complex studies of kidney development and regeneration, we investigated the development and post-injury regeneration of the mesonephros in adult zebrafish." (See also Zebrafish Development)
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Renal Embryology

Karthik Gadabanahalli, Venkatraman Bhat Thoracic Origin of Single Right Renal Artery: Some Interesting Facets. Int. J. Angiol.: 2017, 26(4);264-266 PubMed 29142495

Yousuf M Al Suleimani, Aly M Abdelrahman, Turan Karaca, Priyadarsini Manoj, Mohammed Ashique, Abderrahim Nemmar, Badreldin H Ali The effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on gentamicin nephrotoxicity in mice. Biomed. Pharmacother.: 2017, 97;1102-1108 PubMed 29136947

Ahmed M Kabel, Aliaa Atef, Remon S Estfanous Ameliorative potential of sitagliptin and/or resveratrol on experimentally-induced clear cell renal cell carcinoma. Biomed. Pharmacother.: 2017, 97;667-674 PubMed 29101811

Lara De Tomasi, Pierre David, Camille Humbert, Flora Silbermann, Christelle Arrondel, Frédéric Tores, Stéphane Fouquet, Audrey Desgrange, Olivier Niel, Christine Bole-Feysot, Patrick Nitschké, Joëlle Roume, Marie-Pierre Cordier, Christine Pietrement, Bertrand Isidor, Philippe Khau Van Kien, Marie Gonzales, Marie-Hélène Saint-Frison, Jelena Martinovic, Robert Novo, Juliette Piard, Christelle Cabrol, Ishwar C Verma, Ratna Puri, Hubert Journel, Jacqueline Aziza, Laurent Gavard, Marie-Hélène Said-Menthon, Laurence Heidet, Sophie Saunier, Cécile Jeanpierre Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice. Am. J. Hum. Genet.: 2017, 101(5);803-814 PubMed 29100091

Simone Sanna-Cherchi, Kamal Khan, Rik Westland, Priya Krithivasan, Lorraine Fievet, Hila Milo Rasouly, Iuliana Ionita-Laza, Valentina P Capone, David A Fasel, Krzysztof Kiryluk, Sitharthan Kamalakaran, Monica Bodria, Edgar A Otto, Matthew G Sampson, Christopher E Gillies, Virginia Vega-Warner, Katarina Vukojevic, Igor Pediaditakis, Gabriel S Makar, Adele Mitrotti, Miguel Verbitsky, Jeremiah Martino, Qingxue Liu, Young-Ji Na, Vinicio Goj, Gianluigi Ardissino, Maddalena Gigante, Loreto Gesualdo, Magdalena Janezcko, Marcin Zaniew, Cathy Lee Mendelsohn, Shirlee Shril, Friedhelm Hildebrandt, Joanna A E van Wijk, Adela Arapovic, Marijan Saraga, Landino Allegri, Claudia Izzi, Francesco Scolari, Velibor Tasic, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna-Materna Kiryluk, Shrikant Mane, David B Goldstein, Richard P Lifton, Nicholas Katsanis, Erica E Davis, Ali G Gharavi Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. Am. J. Hum. Genet.: 2017, 101(5);789-802 PubMed 29100090

Objectives

Stage 13 kidney sections.jpg
  • Understand the 3 main stages of kidney development.
  • Understand development of the nephron and renal papilla.
  • Brief understanding of the mechanisms of nephron development.
  • Understand the development of the cloaca, ureter and bladder.
  • Brief understanding of abnormalities of the urinary system.

Textbook References

  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 13 p303-346
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 10 p261-306

Renal Movies

Renal Development

Urogenital sinus 001 icon.jpg
 ‎‎Renal Overview
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Renal 001 icon.jpg
 ‎‎Nephron
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Urogenital septum 001 icon.jpg
 ‎‎Urogenital Septum
Page | Play
Trigone 001 icon.jpg
 ‎‎Trigone
Page | Play
Stage13-GIT-icon.jpg
 ‎‎GIT Stage 13
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Stage22-CNS-icon.jpg
 ‎‎Urogenital
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Renal blood 01 icon.jpg
 ‎‎Renal Vascular
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Background

  • Mesoderm then intermediate mesoderm
  • Vascular Development
  • Gastrointestional
  • Cloacal development
  • Endocrine - covered in future lecture/lab

Kidney Anatomy

Adult nephron structure
  • Nephron - Functional unit of kidney
  • Humans up to 1 million
  • Filtration of waste from blood
  • Endocrine
  • Blood pressure regulation

The key structure of the adult nephron is the glomerulus (renal corpuscle), which represents the initial vascular/renal interface.

Related Images: Nephron histology overview | glomerulus structure | vascular and renal poles


Ureter

  • Bladder - Urine storage
  • Endoderm allantois

Mesoderm

  • Intermediate mesoderm - Lies between somites and lateral plate

Intermediate Mesoderm

Stage7 intermediate-mesoderm.jpg

Week 3 - Stage 7 dorsal view
intermediate mesoderm (orange lateral strips)

Mesoderm-cartoon4.jpg

Cross-section showing mesoderm regions

  • development occurs laterally symmetrical (left right)
  • intermediate mesoderm lying beside the dorsal aorta
  • initially form mesonephric tubules (epithelial)
  • these tubules connect to a common duct, mesonephric duct
  • the mesonephric duct then extends within the mesoderm, rostro-caudally
  • eventually making contact with the cloaca

Mesonephric Duct

Later in development, both the mesonephric duct and the cloaca both continue to differentiate and undergo extensive remodelling (and renaming)

Ureteric Bud

Mouse E12.5 kidney in vitro
  • arise near the cloacal connection of the mesonephric duct
  • branch from the mesonephric duct laterally into the intermediate mesoderm
  • induce the surrounding mesoderm to differentiate - metanephric blastema
    • this mesoderm will in turn signal back to differentiate the ureteric bud

Epithelial - mesenchymal interaction

Ureteric Bud forms - ureter, pelvis, calyces, collecting ducts

Metanephric Blastema

  • forms glomeruli, capsule, nephron tubules
  • this development continues through fetal period

Nephros Development

Three pairs appearing in sequence within intermediate mesoderm during development.

  1. pronephros
  2. mesonephros
  3. metanephros

Pronephros

  • week 4 few cells in cervical region fish
  • Human E18, Mouse E7.5pronephric duct forms first with associated nephrogenic mesenchyme
  • grows rostro caudally cervical -> cloaca
  • E22 nephrogenic mesenchyme differentiates to form pronephroi not functional in mammals degenerates rapidly

Mesonephros

Human E24, Mouse E9.5 caudal to pronephros
  • forms by induction from pronephros
  • pronephric duct now becomes mesonephric duct (also called Wolffian Duct)
  • extends downwards in intermediate mesoderm towards cloaca, later urogenital sinus
Stage 13 kidney sections 2.jpg

Week 5 - Stage 13 mesonephros
(extending the length of the body)

Stage22 mesonephros.jpg

Week 8 - Stage 22 mesonephros
(now degenerating)

Metanephros

Early fetal kidney (week 10)
  • Human E35-37, Mouse E11 epithelia bud at end of mesonephric duct ureteric bud and associated metanephric mesenchyme

Ureteric Bud

  • induced by metanephric mesenchyme to differentiate
  • forms collecting tubules, renal pelvis, ureter
  • metanephric mesenchyme induced by ureteric to differentiate forms nephron

Nephron

In humans, nephrogenesis only occurs before birth, though nephron maturation continues postnatally. Mean glomerular number shown to level at 36 weeks, increasing from about 15,000 at 15 weeks to 740,000 at 40 weeks. Gray1128.jpg

Adult nephron structure

Nephron histology.jpg

Nephron histology

Renal 001 icon.jpg
 ‎‎Nephron
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Nephron development has four identifiable developmental stages:

  1. Vesicle (V) stage (13-19 weeks, second trimester)
  2. S-shaped body (S) stage ( 20-24 weeks, second trimester)
  3. Capillary loop (C) stage (25-29 weeks, third trimester)
  4. Maturation (M) stage (infants aged 1-6 months, neonatal and postnatal)
  • disorganised mesenchymal cells become a highly organised epithelial tubule
  • Condensation - groups of about 100 cells condense tightly together to form a distinct mass
  • Epithelialisation - condensed cells lose their mesenchymal character and gain epithelial
  • At end of this period formed a small epithelial cyst complete with a basement membrane, cell-cell junctions and a defined cellular apico-basal polarity.
Nephron development 01.jpg

Nephron development[8]

  • a - condensed aggregate forms
  • b - renal vesicle forms
  • c - S-shaped body (red), renal progenitors are localised, at this stage podocyte-committed progenitors (red + blue) as well as tubular-committed progenitors (orange) can already be seen.
  • d - mature nephron, renal progenitors (red), podocyte-committed progenitors (red + blue), as well as tubular-committed progenitors (orange) are distributed along the nephron.
  • e - glomerulus, renal progenitors (red) are localized at the urinary pole of the Bowman capsule. Podocyte-committed progenitors (red + blue) localize along the Bowman capsule.
  • cyst invaginates twice to form a comma
  • then a S-shaped body one invagination site later becomes the glomerular cleft
  • At about this time blood vessel progenitors invade cleft to begin construction of vascular component of glomerulus
  • Tubule maturation specialised transporting segments of nephron differentiate complex of convoluted tubules is created
  1. ureteric bud (gray) extends from the mesonephric (Wolffian) duct
  2. upon contact with the metanephric mesenchyme (red), reciprocal signaling induces both bud bifurcation and condensation of the mesenchyme to generate the cap mesenchyme.
  3. blastemal mesenchyme then undergo a MET to generate the renal vesicle
  4. renal vesicle continues to form the comma-shaped and S-shaped body
  5. distal end fuses with the ureteric bud (which forms the collecting duct)
  6. proximal end joins to form the glomerulus, generating the mature nephron (dark orange).
Renal development cartoon01.jpg

Renal Development Interactions[9]

Embryonic Kidney

Embryonic stage descriptions based on Carnegie collection embryos.[10]

Week 4

  • 12 - 29 somite embryo mesonephros tubules begin at the level of somite 8 and are distinct as far caudally as somite 20, whence they extend as a continuous nephrogenic cord to t he level of somite 24. Opposite each somite there are two or more tubules. Thus they are not metameric, any more than the mesonephric duct is metameric, or the umbilical vein. The number of nephric vesicles is being increased by progressive differentiation caudally from the nephrogenic cord.[11] The mesonephric duct at first ends blindly immediately short of the cloaca, but soon becomes attached to the cloaca (i.e., to the terminal part of the hindgut) and acquires a lumen.
  • 13 - Mesonephros glomeruli begin to develop, and nephric tubules become S-shaped.[12] A ureteric bud may possibly be present in some specimens[13] fig. 4), although further confirmation is needed. The mesonephric duct, which becomes separated from the surface ectoderm except in its caudal portion, is fused to the cloaca, into which it may open. A urorectal cleavage line is apparent.

Week 5

  • 14 - In embryos of this stage the mesonephros is well along in its organogenesis. The steps in this process are made easier to follow by the fact that the development occurs progressively in a rostrocaudal direction. Here again is an organ in which the epithelial elements constitute its primary tissue and seem largely to determine its form. The non-epithelial mesonephric elements, though necessary complements for epithelial-mesenchymal interaction, give the appearance of being subsidiary. It has already been seen that the coelomic surface cells possess various inherent potentialities. The surface of the coelom can be mapped in definite areas in accordance with the distribution of these various kinds of surface cells. Running along each side of the median plane is a narrow strip of coelom where, by the proliferation and delamination of its surface cells, there is produced a longitudinal series of epithelial tubules that constitute the units of the mesonephros. This follows the manner in which nephric elements were formed in previous stages, and it is now about to be repeated, with certain modifications, in the development of the metanephros, which is still in the primordial state of a budding ureter with its nephrogenic capsule (fig. 14-6). One can go a step further in regard to the inherent constitution of these coelomic epithelial tubules. Not only do they become tubules, but from the beginning they show regional differentiation. The proximal end promptly blends with and opens into the mesonephric duct, and this part of the tubule persists as a collecting duct. The distal free end at the same time begins its expansion into a highly specialized part of the tubule, namely the mesonephric corpuscle. The intervening central segment of the tubule becomes the convoluted secretory portion. Embryos in this stage are especially favorable for the study of the process of formation of the mesonephric corpuscle. The proliferation of the tubular epithelium at the free end results in its maximum expansion. This occurs in such a way as to produce an indented flattened vesicle, known as a glomerular capsule. As seen in section, it has an arched floor-plate several cells thick and a thin, single-layered roof membrane. The two are continuous with each other but are very different in their potentialities. The roof membrane becomes attenuated as an impermeable membrane. The floor plate continues active proliferation and many of its cells were believed by Streeter to delaminate and apparently become angioblasts, participating in the formation of the vascular glomerulus and its supporting tissues. It is now maintained, however, that the glomerular capillaries (in the metanephros) come from adjacent vessels and never develop in situ from epithelial cells (Potter, 1965). Further details of renal development have been provided by several authors (e.g., Potter, 1972). The residual cells facing the capsular lumen in the mesonephros at stage 14 are reduced in the more advanced phases to a single layer, covering and conforming everywhere to the tabulations of the underlying capillary tufts. Angiogenesis around the secretory part of the tubule is not far advanced. Angiogenic strands connect with the caudal cardinal vein, and throughout the mesonephros there are isolated clumps of angioblasts, particularly around the capsules. These show the typical difference in complexity of the three parts of the tubule: (1) collecting duct, (2) secretory segment, and (3) glomerular capsule.
  • 15 - The ureteric bud is longer, and its tip is expanded as the pelvis of the ureter (fig. 15-10). The primary urogenital sinus is distinguishable.

Week 6

  • 16 - The metanephros, which is now reniform, is still sacral in level. The ureter is elongating and, in more advanced embryos, the pelvis of the ureter divides into rostral and caudal poles. The urorectal septum, the formation of which is disputed, is well marked.
  • 17 - The mesonephros shows epithelial plaques in the visceral layer of the glomerular capsule and hence can produce urine (Silverman, 1969)[14]. The pelvis of the ureter usually shows three main divisions, and calices appear. The urogenital sinus presents a pelvic part (vesico-urethral canal) and a phallic part (definitive urogenital sinus).

Week 7

  • 18 - Collecting tubules develop from the calices at stages 17 and 18. They are surrounded by sharply outlined condensed primordia in the process of forming secretory tubules. Renal corpuscules are not yet present. By stage 18 the mesonephric duct and the ureter open almost independently into the vesico-urethral canal[12]: i.e., the common excretory duct is disappearing. The cloacal membrane is ready to rupture.

Week 8

  • 20 - The external surface of the metanephros is said to be slightly lobulated. A reconstruction of the urinary system has been published by Shikinami[12] (fig. 5).
  • 21 - Metanephros is spoon-shaped glomerular capsules are developing, but no large glomeruli are present yet.
  • 22 - Metanephros has a few large glomeruli present.
  • 23 - Comparison between the mesonephros and the metanephros in staged embryos is lacking. In metanephros, the kidneys have ascended from a sacral level at stages 13–15 to a lumbar level at stages 17–23. At stage 23 they are generally at the level of lumbar vertebrae 1–3..

Fetal Kidney

Fetal kidney MRI 01.jpg MRI appearance of normal fetal kidney.[15] Sagittal T2- SSFSE of a fetal abdomen at GA 25 week. Adequate volume of the amniotic fluid and the developing lungs indicate good renal function.


  • two arrowheads - note the size and the signal appearance of the normal kidney.
  • white arrow - the fluid-filled urinary bladder
  • black arrow - the developing lung.

Note that the urinary bladder can occupy a considerable portion of the abdomen as a normal finding.


Links: Magnetic Resonance Imaging
Fetal nephron development[8]
Fetal nephron development 01.jpg

After nephron development has completed and concomitant with the development of the renal papilla in the newborn, the thin ascending limb of Henle’s loops is generated as an outgrowth from the S3 segment of the proximal tubule and from the distal tubule anlage of the nephron.

Endocrine Kidney

Covered also in Endocrine Development lecture

  • Renin - Increase Angiotensin-aldosterone system
  • Prostaglandins - decrease Na+ reabsorption
  • Erythropoietin - Increase Erythrocyte (rbc) production
  • 1,25 (OH)2 vitamin D - Calcium homeostasis
  • Prekallikreins - (plasma protein inactive precursor of kallikrein) Increase kinin production (altered vascular permeability)

Cloaca

File:Endoderm development

  • hindgut region ending at the cloacal membrane
  • divided (ventro-dorsally) by the urogenital septum
    • ventral - common urogenital sinus
    • dorsal - rectum
Urogenital septum 001 icon.jpg
 ‎‎Urogenital Septum
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Common Urogenital Sinus

  • superior end continuous with allantois
  • common urogenital sinus and mesonephric duct fuse (connect)
  • differentiates to form the bladder
  • inferior end forms urethra
    • this will be different in male and female development

Urinary Bladder

Adult bladder
Trigone 001 icon.jpg
 ‎‎Trigone
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  • early origins of the bladder at the superior end of the common urogenital sinus
  • 8 open inferiorly to the cloaca and superiorly to the allantois
  • Septation of the claoca - divides the anterior region to the primordial bladder component from the posterior rectal component.
  • associated ureters and urethra

Dorsal view of developing bladder

  • Ultrasound measurement of the bladder size can be used as a diagnostic tool for developmental abnormalities.

Bladder Structure

Bladder histology

Can be described anatomically by its 4 layers from outside inward:

  • Serous - the superior or abdominal surfaces and the lateral" surfaces of the bladder are covered by visceral peritoneum, the serous membrane (serosa) of the abdominal cavity, consisting of mesthelium and elastic fibrous connective tissue.
  • Muscular - the detrusor muscle is the muscle of the urinary bladder wall.
  • Submucosa - connects the muscular layer with the mucous layer.
  • Mucosa - (mucus layer) a transitional epithelium layer formed into folds (rugae).

Detrusor Muscle

  • The adult detrusor muscle consists of three layers of smooth (involuntary) muscle fibres.
    • external layer - fibres arranged longitudinally
    • middle layer - fibres arranged circularly
    • internal layer - fibres arranged longitudinally

Ureter Development

  • The adult ureter is a thick-walled muscular tube, 25 - 30 cm in length, running from the kidney to the urinary bladder.
  • Anatomically can be described in two parts the abdominal part (pars abdominalis) and pelvic part (pars pelvina).
  • The ureter is composed of three layers: outer fibrous layer (tunica adventitia), muscular layer (tunica muscularis) and mucous layer (tunica mucosa).
  • The muscular layer can also be subdivided into 3 fibre layers: an external longitudinal, a middle circular, and an internal longitudinal.

Trigone Development

Trigone 001 icon.jpg
 ‎‎Trigone
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Kidney Ascent

early fetal kidney
Renal blood 01 icon.jpg
 ‎‎Renal Vascular
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  • Pro-, Meso-, Meta- Early development descending
  • Metanephros - initially pelvic, beside aorta
  • Growth and straightening of body - Kidneys in abdomen and displace laterally

Renal Arteries

  • Arise with ascent and inferior branches lost
  • Sequential, 25% population have 2 or more renal arteries
  • branch of abdominal aorta, divides into 4-5 branches
    • each gives off small branches to suprarenal glands, ureter, surrounding cellular tissue and muscles

Note: Frequently a second renal artery (inferior renal) from abdominal aorta at a lower level, supplies lower portion of kidney

Abnormalities

Australian renal abnormalities

There are many different forms of renal development abnormalities associated with kidney, ureters, bladder and urethra. There are many genetic disorders associated with failure or abnormal renal development. Prenatal diagnosis of obstructive and renal agenesis/dysgenesis disorders are also important for early reproductive decisions by the parents. For example, with bilateral renal agenesis, failure of both kidneys to development, is not compatible with fetal/neonatal survival. Because of their close developmental association, often described as the urogenital system, there can be an associated genital abnormalities.


More detailed information is available on the links below.


Links: Renal Abnormalities | Genital Abnormalities

Horseshoe Kidney

Horseshoe kidney
  • fusion of the lower poles of the kidney.
  • During migration from the sacral region the two metanephric blastemas can come into contact, mainly at the lower pole.
  • The ureters pass in front of the zone of fusion of the kidneys.
  • The kidneys and ureters usually function adequately but there is an increased incidence of upper urinary tract obstruction or infection.
  • Some horseshoe variations have been described as having associated ureter abnormalities including duplications.

Urorectal Septum Malformation

  • thought to be a deficiency in caudal mesoderm which in turn leads to the malformation of the urorectal septum and other structures in the pelvic region.
  • Recent research has also identified the potential presence of a persistent urachus prior to septation of the cloaca (common urogenital sinus).

Bladder

  • absent or small bladder - associated with renal agenesis.

Bladder Exstrophy

Bladder_Exstrophy
  • developmental abnormality associated with bladder development.
  • origins appear to occur not just by abnormal bladder development, but by a congenital malformation of the ventral wall of abdomen (between umbilicus and pubic symphysis).
  • There may also be other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).

Ureter and Urethra

  • Ureter - Duplex Ureter
  • Urethra- Urethral Obstruction and Hypospadias


Polycystic Kidney Disease

Multicystic kidney
  • diffuse cystic malformation of both kidneys
  • cystic malformations of liver and lung often associated, Often familial disposition
  • Two types
    • Infantile (inconsistent with prolonged survival)
    • Adult (less severe and allows survival)
  • Autosomal dominant PKD disease - recently identified at mutations in 2 different human genes encoding membrane proteins (possibly channels)

Wilms' Tumor

  • (nephroblastoma) Named after Max Wilms, a German doctor who wrote first medical articles 1899
  • most common type of kidney cancer children
  • WT1 gene - encodes a zinc finger protein
  • Both constitutional and somatic mutations disrupting the DNA-binding domain of WT1 result in a potentially dominant-negative phenotype
  • some blastema cells (mass of undifferentiated cells) persist to form a ‘nephrogenic rest’
  • Most rests become dormant or regress but others proliferate to form hyperplastic rests
  • any type of rest can then undergo a genetic or epigenetic change to become a neoplastic rest
  • can proliferate further to produce a benign lesion (adenomatous rest) or a malignant Wilms’ tumour


Prune Belly Syndrome

  • lower urinary tract obstruction
  • mainly male
  • fetal urinary system ruptures leading to collapse and "prune belly" appearance.

Renal Cysts

The Bosniak classification system (Category I - IV) was designed to separate identified cystic renal masses by analysis of computed tomography (CT) features into surgical and nonsurgical categories.[16] Named after Morton Bosniak, Yale University School of Medicine, the developer of this classification system.

Molecular

Abbreviation Growth Factor Renal Development Expression Location
BMP4 Bone Morphogenetic Protein 4 prevents ectopic ureteric bud outgrowth and extra ureteric bud divisions mesenchymal cells surrounding mesonephric duct and stromal mesenchyme surrounding steric bud stalks
BMP7 Bone Morphogenetic Protein 7 survival of metanephric mesenchyme metanephric mesenchyme
Fgf8 Fibroblast Growth Factor 8 transition of the induced cap mesenchyme into RVs cap mesenchyme
GDNF Glial-cell derived neurotrophic factor induces steric bud outgrowth from mesonephric duct, interacts with Ret metanephric mesenchyme
VEGF Vascular endothelial growth factor promotes endothelial cell proliferation, differentiation s-shaped body
Wnt4 Wingless-Type MMTV Integration Site Family, Member 4 mesenchymal-to-epithelial transition cap metanephric mesenchyme, pre-tubular aggregate, nephron progenitors
Wnt5a Wingless-Type MMTV Integration Site Family, Member 5a nephrogenesis induction, ectopic bud formation steric bud, metanephric mesenchyme
Wnt9b Wingless-type MMTV integration site family, Member 9B renewal and differentiation of nephron progenitors and normal ureteric bud branching, mesenchymal-to-epithelial transition steric bud stalk epithelial cells
  • Foxd1 - (Brain Factor-2) transcription factor that is a renal stroma specific gene.
Links: Renal System - Molecular | OMIM Foxd1

References

  1. J R Nyengaard, T F Bendtsen Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat. Rec.: 1992, 232(2);194-201 PubMed 1546799
  2. M F Schreuder, J Nauta Prenatal programming of nephron number and blood pressure. Kidney Int.: 2007, 72(3);265-8 PubMed 17495859
  3. Kun Xu, Xinyu Wu, Ellen Shapiro, Honging Huang, Lixia Zhang, Duane Hickling, Yan Deng, Peng Lee, Juan Li, Herbert Lepor, Irina Grishina Bmp7 functions via a polarity mechanism to promote cloacal septation. PLoS ONE: 2012, 7(1);e29372 PubMed 22253716
  4. Shaowei Chen, Xiao Yao, Yuwen Li, Zubaida Saifudeen, Dimcho Bachvarov, Samir S El-Dahr Histone deacetylase 1 and 2 regulate Wnt and p53 pathways in the ureteric bud epithelium. Development: 2015, 142(6);1180-92 PubMed 25758227
  5. Kun Xu, Xinyu Wu, Ellen Shapiro, Honging Huang, Lixia Zhang, Duane Hickling, Yan Deng, Peng Lee, Juan Li, Herbert Lepor, Irina Grishina Bmp7 functions via a polarity mechanism to promote cloacal septation. PLoS ONE: 2012, 7(1);e29372 PubMed 22253716
  6. Osman Sulak, Gülnur Ozgüner, Mehmet Ali Malas Size and location of the kidneys during the fetal period. Surg Radiol Anat: 2011, 33(5);381-8 PubMed 21110022
  7. Weibin Zhou, Rudrick C Boucher, Frank Bollig, Christoph Englert, Friedhelm Hildebrandt Characterization of mesonephric development and regeneration using transgenic zebrafish. Am. J. Physiol. Renal Physiol.: 2010, 299(5);F1040-7 PubMed 20810610
  8. 8.0 8.1 Paola Romagnani, Laura Lasagni, Giuseppe Remuzzi Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol: 2013, 9(3);137-46 PubMed 23338209
  9. Peter Hohenstein, Kathy Pritchard-Jones, Jocelyn Charlton The yin and yang of kidney development and Wilms' tumors. Genes Dev.: 2015, 29(5);467-82 PubMed 25737276
  10. O'Rahilly R. and Müller F. Developmental Stages in Human Embryos. Contrib. Embryol., Carnegie Inst. Wash. 637 (1987).
  11. Torrey TW. The early development of the human nephros. (1954) Contrib. Embryol., Carnegie Inst. Wash. Publ. 603, 35: 175-197.
  12. 12.0 12.1 12.2 Shikinami J. Detailed form of the Wolffian body in human embryos of the first eight weeks. (1926) Contrib. Embryol., Carnegie Inst. Wash. Publ. 363, 18: 46-61.
  13. Wells LJ. Development of the human diaphragm and pleural sacs. (1954) Contrib. Embryol., Carnegie Inst. Wash. Publ. 603, 35: 107-134.
  14. H Silverman [The development of the epithelial plaques in the renal corpuscles of the human embryonic kidney]. [Uber die Entwicklung der Epithelplatten in den Corpuscula renalia der menschlichen Urniere.] Acta Anat (Basel): 1969, 74(1);36-43 PubMed 5374935
  15. Sahar N Saleem Fetal MRI: An approach to practice: A review. J Advanc Res: 2014, 5(5);507-23 PubMed 25685519 | J Adv Res.
  16. Gary M Israel, Morton A Bosniak How I do it: evaluating renal masses. Radiology: 2005, 236(2);441-50 PubMed 16040900 | Radiology

Textbooks

  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 13 p303-346
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 10 p261-306
  • Before We Are Born (5th ed.) Moore and Persaud Chapter14 p289-326
  • Essentials of Human Embryology, Larson Chapter 10 p173-205
  • Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 p134-152

Online Textbooks

Search Bookshelf intermediate mesoderm | kidney development | renal development | ureteric bud | nephron development | bladder development

Reviews

Peter Hohenstein, Kathy Pritchard-Jones, Jocelyn Charlton The yin and yang of kidney development and Wilms' tumors. Genes Dev.: 2015, 29(5);467-82 PubMed 25737276

Melissa Little, Kylie Georgas, David Pennisi, Lorine Wilkinson Kidney development: two tales of tubulogenesis. Curr. Top. Dev. Biol.: 2010, 90;193-229 PubMed 20691850

Gregory R Dressler Advances in early kidney specification, development and patterning. Development: 2009, 136(23);3863-74 PubMed 19906853

Odyssé Michos Kidney development: from ureteric bud formation to branching morphogenesis. Curr. Opin. Genet. Dev.: 2009, 19(5);484-90 PubMed 19828308

Kimberly J Reidy, Norman D Rosenblum Cell and molecular biology of kidney development. Semin. Nephrol.: 2009, 29(4);321-37 PubMed 19615554

Susan E Quaggin, Jordan A Kreidberg Development of the renal glomerulus: good neighbors and good fences. Development: 2008, 135(4);609-20 PubMed 18184729

Andrea Brenner-Anantharam, Cristina Cebrian, Richard Guillaume, Romulo Hurtado, Tung-Tien Sun, Doris Herzlinger Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling. Development: 2007, 134(10);1967-75 PubMed 17442697

Forefronts Symposium on Nephrogenetics: from development to physiology March 8-11, 2007 Danvers, MA A meeting to synthesize an integrated view of the normal development and function of the kidney from the genetic standpoint.

Frank Costantini Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation: 2006, 74(7);402-21 PubMed 16916378


Articles

Mor Grinstein, Ronit Yelin, Doris Herzlinger, Thomas M Schultheiss Generation of the podocyte and tubular components of an amniote kidney: timing of specification and a role for Wnt signaling. Development: 2013, 140(22);4565-73 PubMed 24154527

Malin M Rhodin, Brian J Anderson, A Michael Peters, Malcolm G Coulthard, Barry Wilkins, Michael Cole, Etienne Chatelut, Anders Grubb, Gareth J Veal, Michael J Keir, Nick H G Holford Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr. Nephrol.: 2009, 24(1);67-76 PubMed 18846389


Search PubMed

Search Pubmed: Renal System Development | Renal Development | intermediate mesoderm | kidney development | renal development | ureteric bud | nephron development | bladder development

Additional Images

Terms

Open table below to see list of renal terms.

Renal Terms  
  • bladder exstrophy - A congenital malformation with bladder open to ventral wall of abdomen (between umbilicus and pubic symphysis) and may have other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).
  • blastema - Term used to describe a mass of undifferentiated cells. (More? Wilm's tumour)
  • Bowman's capsule - (capsula glomeruli, glomerular capsule) Surrounds the glomerulus within the nephron with a vascular and urinary pole and is the beginning of the tubular component. Named in 1842 after Sir William Bowman (1816 – 1892) an English surgeon and anatomist.
  • Brenner hypothesis - a clinical hypothesis that states, individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure. Developed in the 1980's by Barry Brenner at the Brigham and Women's Hospital, this also fits with the DOHAD hypothesis. (More? PubMed 3063284 | Barry Brenner)
  • capillary loop - (C stage) The third stage in nephron development between 25-29 weeks. (stage sequence: V - S - C - M)
  • diabetes insipidus - The disorder is related to the hormone antidiuretic hormone (ADH, also called vasopressin) its synthesis, secretion, receptors and signaling pathway. In diabetes insipidus there is an excretion of large amounts (up to 30 litres/day) of a watery urine and an unremitting thirst.
  • fenestrated capillary - Specialised capillaries containing circular pores (fenestrae) that penetrate the endothelium, may be closed by a thin diaphragm.
  • glomerulus - The capillary network (tuft) within Bowman's capsule of the nephron enters at the vascular pole (afferent and efferent arteriole).
  • hydronephrosis - (congenital hydronephrosis, Greek, hydro = water) A kidney abnormality due to partial or complete obstruction at the pelvi-ureteric junction. This leads to a grossly dilated renal pelvis causing extensive renal damage before birth.
  • hyperplastic rests - In kidney development, embryonic blastema cells can persist and proliferate to form a pool of cells, which under either genetic or epigenetic influence can then change to become a neoplastic rest. Normally the majority of nephrogenic rests either regress or become dormant.
  • juxtaglomerular cells - Cells located at the vascular pole that secrete renin and form a part of the juxtaglomerular complex.
  • loop of Henle - Nephron region spanning from the proximal convoluted tubule to the distal convoluted tubule. Named after Named after Friedrich Gustav Jakob Henle (1809–1885) a German anatomist.
  • macula densa - Columnar cell cluster appearing as a dense row of cell nuclei where the straight portion of the distal tubule contacts the glomerulus. Region also in close contact with the efferent and afferent arterioles of the glomerulus and involved in sodium chloride regulation. (More? image)
  • maturation stage - (M stage) The forth stage in nephron development in infants aged 1-6 months. (stage sequence: V - S - C - M)
  • mesangial cells - Cells in the nephron glomerulus that form the connective tissue giving structural support to podocytes and vessels.
  • mesonephros - The second temporary stage of kidney development (pro-, meso-, meta-). The intermediate mesonephros develops and disappears with the exception of its duct, the mesonephric duct, which will form the male reproductive duct system. In males, the mesonephric tubules go on to form the ducts of the testis. In females, these degenerate. A few mesonephric tubules remain as efferent ductules in the male and vestigial remnants in the female.
  • mesonephric duct - (= Wollfian duct) An early developing urogenital duct running the length of the embryo that will differentiate and form the male reproductive duct system. In females this duct degenerates (some remnants may remain associated in broad ligament).
  • metanephros - The adult kidney, third stage of mammalian kidney (pro-, meso-, meta-) development within the intermediate mesoderm.
  • metanephric cap - (metanephric blastema) The intermediate mesoderm which surrounds the ureteric bud and will contribute most of the adult nephron.
  • multicystic kidney - There is no functional kidney tissue present in the kidney and it is replaced by a multilocular cyst. This is non-familial and is produced by atresia of a ureter and is always unilateral.
  • neoplastic rest - In kidney development, a neoplastic rest can develop under either genetic or epigenetic influence from a hyperplastic rest, originating from an embryonic blastema cell. Normally the majority of nephrogenic rests either regress or become dormant.
  • nephrogenic rest - Used to describe the embryonic blastema cells which persist and under either genetic or epigenetic can change to become a neoplastic rest. These neoplastic rests can develop postnatally as a benign form (adenomatous rest) or a malignant Wilm's tumour form. The rests are further characterised by the time of generation leading to different anatomical kidney locations: early intralobar nephrogenic rests (within the renal lobe) and late pelilobar nephrogenic rests (periphery of the renal lobe)
  • nephron - (Greek, nephros = kidney) The functional unit of the adult kidney.
  • nephros - (Greek, nephros = kidney) Term used to describe features associated with the kidney. (pronephros, mesonephros, metanephros, nephric, nephron, nephroblastoma).
  • parietal layer - Cells of the outer of Bowman's capsule that form a simple squamous epithelium. The inner layer is the visceral layer.
  • podocyte - (visceral epithelial cell) kidney glomerulus cell forming the main component of the glomerular filtration barrier. (glomerular podocyte) Kidney epithelial cell type in the nephron (kidney functional unit) located in the glomerulus. Podocytes form the visceral layer of Bowman's capsule and are at the filtration barrier between capillary blood and the nephron tubular system and function to ultrafiltrate blood, and support glomerular capillary pressures. The differentiation of podocytes involves the formation of cellular foot processes and then the slit membrane. (More? image)
  • podocyte specific proteins - podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2).
  • pronephros - (Greek, pro = before) The first temporary stage of kidney development (pro-, meso-, meta-). This forms the kidney of primitive fish and lower vertebrates. Kidney development occurs within the intermediate mesoderm interacting with endoderm. In humans, this very rudimentary kidney forms very early at the level of the neck. It is rapidly replaced by the mesonephros, intermediate stage kidney, differentiating in mesoderm beneath.
  • proteinuria - The abnormal presence of protein in the urine and an indicator of diesease including diabetic kidney disease (DKD, diabetic nephropathy).
  • proximal tubule - Portion of the nephron duct between Bowman's capsule to the loop of Henle, divided into the proximal convoluted tubule (PCT) and the proximal straight tubule (PST).
  • renal - (Latin, renes = kidney) Term used in relation to the kidney and associated structures (renal pelvis, renal artery)
  • S-shaped body - (S stage) The second stage in nephron development between 20-24 weeks. (stage sequence: V - S - C - M)
  • transitional epithelium - (urothelium) Histological term to describe the epithelium lining the ureters and urinary bladder. (More? image)
  • trigone - refers to the urinary bladder triangular region formed by the two ureters and the urethra.
  • ureter - The two ureters are hollow tubes that link the kidney and the bladder and carry urine. They develop from the ureteric bud and are lined by a transitional epithelium with an outer muscular wall.
  • urethra - The single muscular tube that links and carries urine from the bladder to the exterior. In humans, the urethral length differs between the sexes (male longer, female shorter).
  • vascular pole - The side of nephron Bowman's capsule where the afferent arteriole and efferent arteriole enter the glomerulus. image
  • visceral layer - Cells (podocytes) of the inner of Bowman's capsule that form extremely complex shapes. Cytoplasm form a fenestrated epithelium around the fenestrated capillaries of the glomerulus. The outer layer is the parietal layer.
  • vesicle stage - (V stage) The first stage in nephron development between 13-19 weeks. (stage sequence: V - S - C - M)
  • urinary - Term used to describe all components of the kidney system including the bladder, ureters and urethra.
  • urinary pole - The side of nephron Bowman's capsule where the proximal convoluted tubule starts. image
  • urine - Term used to describe the liquid waste produced by the kidney, stored in the bladder and excreted from teh body through the urethra.
  • urorectal septum - (URS) The structure which develops to separate the cloaca (common urogenital sinus) into an anterior urinary part and a posterior rectal part.
  • Wilms' tumour - A form of kidney/renal cancer (nephroblastoma) named after Dr Max Wilms who first described the tumor. This childhood kidney cancer is caused by the inactivation of a tumour suppressor gene (BRCA2) or Wilms tumor-1 gene (Wt1) and is one of the most common solid tumors of childhood, occurring in 1 in 10,000 children and accounting for 8% of childhood cancers. Wt1 also required at early stages of gonadal development. (More? OMIM - Wilm's tumour | Dr Max Wilms)
  • Wilms' tumor 1-associating protein - (WTAP) protein expressed in extraembryonic tissues and required for the formation of embryonic mesoderm and endoderm.
  • Wolffian duct - (= mesonephric duct, preferred terminology), runs from the mesonephros to cloaca, differentiates to form the male vas deferens and in the female regresses. Named after Caspar Friedrich Wolff (1733-1794), a German scientist and early embryology researcher and is said to have established the doctrine of germ layers. (More? Caspar Friedrich Wolff)
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Cite this page: Hill, M.A. 2017 Embryology Renal System Development. Retrieved November 23, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Renal_System_Development

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