Renal System - Abnormalities

Introduction

Obstructive Defect of the Renal Pelvis

How and why do things go wrong in development?

Some Recent Findings

Trisomy 21 newborn

Congenital urological anomalies diagnosed in adulthood "Despite worldwide availability of prenatal ultrasound, many patients are diagnosed in adult life with congenital anomalies such as ureteropelvic junction obstruction (UPJO), undescended testicle (UDT), ureterocele, hypospadias, vesicoureteral reflux (VUR) and primary obstructing megaureter (POM)." Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis "Mice lacking both Etv4 alleles and one Etv5 allele show either renal agenesis or severe hypodysplasia, whereas kidney development fails completely in double homozygotes. We identified several genes whose expression in the ureteric bud depends on Etv4 and Etv5, including Cxcr4, Myb, Met and Mmp14. Thus, Etv4 and Etv5 are key components of a gene network downstream of Ret that promotes and controls renal branching morphogenesis."

Australian Statistics

Statistics - Top Ten

Australian Data 1981-92

The ten most frequently reported birth defects in Victoria between 2003-2004 (More? Australian Statistics - Victoria)

1. Hypospadias
2. Obstructive Defects of the Renal Pelvis or Obstructive Genitourinary Defects
3. Ventricular Septal Defect
4. Congenital Dislocated Hip
5. Trisomy 21 or Down syndrome
6. Hydrocephalus
7. Cleft Palate
8. Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued.
9. Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%).
10. Cleft Lip and Palate - occur with another defect in 33.7% of cases.

Obstructive Renal Pelvis Defect

Obstructive Renal Pelvis Defect (obstructive defects of the renal pelvis, uteropelvic junction obstruction, pelvo-uterero junction obstruction) is a term describing a developmental renal abnormality due to partial or complete blockage of the drainage of the kidney pelvis requiring surgical correction.

The blockage can also have several causes including:

1. ureter twisting or bending
2. ureter compression by a blood vessel
3. malformations of the muscular wall

The blockage leads to an accumulation of urine in the affected region, with several potential effects: nephron damage from compression (hydronephrosis); decreased urine output leading to lack of amniotic fluid (oligohydramnios); respiratory development effects due to the lack of amniotic fluid. The most common type of obstruction is at the uteropelvic junction (UPJ), between the junction of the ureter and the kidney. Blockage lower as the ureter enters the bladder, the ureterovesicular junction (UVJ), usually involves only one kidney and the back flow enlarges the affected ureter (megaureter).

Renal Agenesis/Dysgenesis

In the complete form the child is not viable and dies within a few days of birth.

Features associated with this anomaly are:

• Oligohydramnios
• Amnion nodosum (small warty amnion with accretions of squamous cells on the inner wall). This is tangible evidence for oligohydramnios.
• Facial deformities: This results from uterine moulding around the head. The ears are low slung and simple, the mandible is small, the nose flattened and the eyes exhibit Pre-epicanthic folds. This is a horseshoe shaped flap of skin from the upper lid to the cheek in front of the epicanthus. (Downs syndrome has an epicanthic fold). Note that the genesis is occasionally incomplete allowing survival (e.g.) Causal factors are largely unknown although there is some familial predisposition. There has been described a mutation in the enzyme, heparan sulfate 2-sulfotransferase, that generates a similar phenotype in the mouse.

Note that upper G.I.T. obstruction is associated with POLYHYDRAMNIOS whereas failure of fetal micturition is associated with OLIGOHYDRAMNIOS with consequent firm uterine moulding on the fetus, leading to facial, locomotor and palatal deformities.

Links: OMIM - UROGENITAL ADYSPLASIA, HEREDITARY

Renal Fusion

Also described as 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.

Triad Syndrome

Also described as Prune Belly Syndrome.

The Triad is:

1. Agenesis of abdominal wall muscles
2. Bladder outflow obstruction
3. Bilateral undescended testes

The condition was first described by Frolichand then called "prune belly syndrome" as a descriptive, because the intestinal pattern is evident through the thin protruding abdominal wall in the infant.

Survival of the prune belly child depends on the number of functioning remaining nephrons at birth and the operability of the obstruction.

In some cases there are vestiges of muscle in the abdominal wall and it is not known whether this represents (a) destruction of muscle, or (b) failure of development of muscle. The causes of this malformation are little known, but maternal therapy with estrogens in the first trimester has been implicated frequently.

• 
• 
• 

  Prune_belly

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)

Nephroblastoma (Wilms' Tumor)

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

Urorectal Septum Malformation

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).

Clinically the condition is described as a urorectal septum malformation sequence (URSMS): female disorder of sexual development; ambiguous external genitalia; imperforate anus, vagina, and urethra; renal, colonic, and lumbosacral anomalies.

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).

Bladder

• absent or small bladder - associated with renal agenesis.

Ureterocele

The distal ureter balloons at the opening into the bladder and forms a sac-like pouch. Often associated with other ureter abnormalities.

Ureter and Urethra

Ectopic and dilated left ureter (small arrows) inserting ectopically into the obstructed left hemivagina (asterisk) on MR imaging in a 17-year-old girl.

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

See also Genital System - Abnormalities

References

Search Pubmed

Search Pubmed: Obstructive Renal Pelvis Defects | Renal Agenesis | hydronephrosis

Terms

cystic dysplasia - term used in renal dysplasia if cysts are present.

renal agenesis - complete absence of renal development.

renal dysgenesis - abnormal kidney development, which includes aplasia, hypoplasia, dysplasia, and cystic disease.

renal aplasia - rudimentary kidney without any functional nephrons.

renal hypoplasia - small non-dysplastic kidney that has less than the normal number of calyces and nephrons.

renal dysplasia - focal, diffuse, or segmentally arranged primitive structures, specifically primitive ducts, resulting from abnormal metanephric differentiation. Non-renal elements, such as cartilage, may be present.

renal adysplasia - term is used when aplasia and severe dysplasia are aspects of phenotypic spectrum.

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

---

Cite this page: Hill, M.A. (2024, May 9) Embryology Renal System - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Renal_System_-_Abnormalities

What Links Here?

© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G