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Renal agenesis is a medical condition in which one (unilateral) or both (bilateral) fetal
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s fail to develop. Unilateral and bilateral renal agenesis in humans, mice and zebra fish has been linked to mutations in the gene GREB1L. It has also been associated with mutations in the genes '' RET'' or '' UPK3A'' in humans and mice respectively.


Type


Bilateral

Bilateral renal agenesis is a condition in which both
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s of a fetus fail to develop during
gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregn ...
. It is incompatible with life. It is one causative agent of
Potter sequence Potter sequence is the atypical physical appearance of a baby due to oligohydramnios experienced when in the uterus. It includes clubbed feet, pulmonary hypoplasia and cranial anomalies related to the oligohydramnios. Oligohydramnios is the dec ...
. This absence of kidneys causes
oligohydramnios Oligohydramnios is a medical condition in pregnancy characterized by a deficiency of amniotic fluid, the fluid that surrounds the fetus in the abdomen, in the amniotic sac. It is typically diagnosed by ultrasound when the amniotic fluid index (A ...
, a deficiency of amniotic fluid in a pregnant woman, which can place extra pressure on the developing baby and cause further malformations. The condition is frequently, but not always the result of a
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
, and is more common in infants born to one or more parents with a malformed or absent kidney.


Unilateral

This is much more common, but is not usually of any major health consequence, as long as the single kidney is healthy. However, this kidney tends to be hypertrophied, ectopic and prone to infection and damage. It may be associated with an increased incidence of Müllerian duct abnormalities, which are abnormalities of the development of the female reproductive tract and can be a cause of
infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal stat ...
, blocked menstrual flow ( hematocolpos), increased need for Caesarean sections, or other problems. Herlyn-Werner-Wunderlich syndrome is one such syndrome in which unilateral renal agenesis is combined with a blind hemivagina and uterus didelphys. Up to 40% of women with a urogenital tract anomaly also have an associated renal tract anomaly. Adults with unilateral renal agenesis have considerably higher chances of
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
(high blood pressure). People with this condition are advised to approach contact sports with caution. A possible complication later in life of unilateral renal agenesis is Focal Segmental Glomerular Sclerosis (FSGS) which will cause nephrotic syndrome, potentially resulting from glomerular overload.


Genetics

In 2008 researchers found
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
mutations in the RET and
GDNF Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particul ...
genes to be linked to renal agenesis in unrelated stillborn fetuses through PCR and direct sequence analysis. In the study, DNA from 33 stillborn fetuses were sequenced for mutations in RET, GDNF and GFRA1. Nineteen of the fetuses had BRA, ten had URA and 4 had congenital renal dysplasia. Seven of the 19 BRA fetuses were found to have a mutation in the RET gene (37%), while two of the ten URA fetuses did (20%). One of the URA fetuses had two RET mutations and one GDNF mutation. There were no GFRA1 mutations found. However, the results of Skinner et al. study were questioned by a more recent study with a larger number of cases. In this study 105 fetuses were analyzed. Sixty-five fetuses had BRA while 24 had URA with an abnormal contralateral kidney. Mutations in the RET gene were only found in seven of the fetuses (6.6%). In 2014 researchers found
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...
mutations in
ITGA8 Integrin alpha-8 is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reac ...
in three members of two unrelated families utilizing
Exome Sequencing Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome (known as the exome). It consists of two steps: the first step is to select only the subset ...
. One of the families was
consanguineous Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor). Many jurisdictions have laws prohibiting people who are related by blood f ...
. In 2017 researchers identified heritable autosomal dominant mutations in the gene GREB1L in two unrelated families as being the cause of both BRA and URA utilizing Exome Sequencing and direct sequencing analysis. This is the first reported genetic lesion implicated in the activation of Retinoic Acid Receptor (RAR) Targets that has been associated with renal agenesis in humans. The researchers found two different GREB1L mutations, each being unique to their respective pedigrees. In total, there were 23 individuals analyzed between the two families, four of which had BRA and five of which had URA. GREB1L mutations were identified in all of the affected individuals as well as in three unaffected family members, demonstrating incomplete penetrance and variable expressivity. There are several hundred to perhaps several thousand genes that, if they had the right kind of mutation, could lead to renal agenesis in humans. It is possible that each individual or family experiencing renal agenesis has a unique gene or genetic mutation causing the condition due to the fact that there are so many genes that are critical to proper renal development. Chromosomal anomalies have been associated with BRA in certain cases (chromosomes 1, 2, 5 and 21), but these anomalies were not inherited and have not been observed in subsequent cases. Additionally, neither extreme substance abuse or environmental factors (high power line, mercury, ground water issues, etc.) have been reported to be linked to an increased incidence of BRA or other cause of Potter sequence. However, renal agenesis and other causes of oligohydramnios sequence have been linked to a number of other conditions and syndromes to include
Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
, Kallmann syndrome,
branchio-oto-renal syndrome Branchio-oto-renal syndrome (BOR) is an autosomal dominant genetic disorder involving the kidneys, ears, and neck. It often has also been described as Melnick-Fraser syndrome. Signs and symptoms The signs and symptoms of branchio-oto-renal syndrom ...
and others.


Prevalence

The prevalence of unilateral renal agenesis in the population is approximately 1 in about 1000 people. Bilateral agenesis occurs in 1 in about 2500 foetuses.


References


External links

{{DEFAULTSORT:Renal Agenesis Kidney diseases Congenital disorders of urinary system