|Other names: Renal agenesis|
|Symptoms||One kidney: None, high blood pressure, kidney failure|
Both kidneys: Poor lung development, death shortly after birth
|Usual onset||Present at birth|
|Risk factors||Genetic mutation, diabetes or certain medication during pregnancy|
|Diagnostic method||Medical imaging|
|Differential diagnosis||Kidney dysplasia, surgical removal|
|Treatment||Regular monitoring, treatment of high blood pressure|
|Frequency||1 in 2,000 (one kidney), 1 in 8,500 (both kidneys)|
Kidney agenesis is a birth defect in which one or both kidneys fail to develop. If only one kidney is involved, many people have no symptoms, though some develop high blood pressure and kidney failure. If both kidneys are absent, the lungs will fail to develop and the child will die shortly after birth.
A number of genetic mutations, such as in the RET proto-oncogene, can result in the condition. Some cases run in families in either an autosomal dominant or autosomal recessive pattern. Other risk factors include diabetes and the use of certain medication during pregnancy. Diagnosis may occur before or after birth via medical imaging.
Among those with a single kidney, regular monitoring of kidney function and blood pressure is recommended. If high blood pressure is present ACE inhibitors may be recommended. About 1 in 2,000 people have a single kidney affected and about 1 in 8,500 have both kidneys are affected. Both kidneys are affected more often in males than females.
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, blocked menstrual flow (hematocolpos), increased need for Caesarean sections, or other problems. Herlyn-Werner-Wunderlich syndrome is one such syndrome in which unilaterial 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.
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.
Bilateral renal agenesis is a condition in which both kidneys of a fetus fail to develop during gestation. It is incompatible with life. It is one causative agent of Potter sequence. This absence of kidneys causes oligohydramnios, 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, and is more common in infants born to one or more parents with a malformed or absent kidney.
Unilateral and bilateral kidney 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.
In 2008 researchers found autosomal dominant mutations in the RET and GDNF 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 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, Kallmann syndrome, branchio-oto-renal syndrome and others.
The prevalence of unilateral renal agenesis in the population is approximately 1 in about 1000 people. Bilateral agenesis occurs in 1 in about 2500 fetuses.
- "Renal agenesis | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 18 March 2021. Retrieved 24 January 2021.
- "Solitary or Single-functioning Kidney | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Archived from the original on 9 January 2021. Retrieved 24 January 2021.
- "Renal Agenesis, Bilateral". NORD (National Organization for Rare Disorders). Archived from the original on 19 February 2017. Retrieved 24 January 2021.
- Lote, Christopher J. (2012). Principles of Renal Physiology, 5th edition. Springer. p. 22.
- Ahmad, Zohra; Goyal, Ankur; Das, Chandan J; Deka, Dipika; Sharma, Raju (2013-01-01). "Herlyn–Werner–Wunderlich syndrome presenting with infertility: Role of MRI in diagnosis". The Indian Journal of Radiology & Imaging. 23 (3): 243–246. doi:10.4103/0971-3026.120283. ISSN 0971-3026. PMC 3843333. PMID 24347855.
- Daoub, Ahmed; Drake, Thomas M. (2014-01-01). "Congenital abnormalities of the urogenital tract: the clue is in the cord?". BMJ Case Reports. 2014: bcr2014208172. doi:10.1136/bcr-2014-208172. ISSN 1757-790X. PMC 4256657. PMID 25465462.
- Sharp, DS; Ross, JH (2002). "Kay". R. 168 (4): 1811–1815. doi:10.1016/s0022-5347(05)64420-5. Archived from the original on October 18, 2014. Retrieved October 11, 2014.
- Kiprov, DD; Colvin, RB; McCluskey, RT (March 1982). "Focal and segmental glomerulosclerosis and porteinuria associated with unilateral renal agenesis". Laboratory Investigation; A Journal of Technical Methods and Pathology. 46 (3): 275–81. PMID 7062725.
- Brophy PD, Rasmussen M, Parida M, Bonde G, Darbro BW, Hong X, Clarke JC, Peterson KA, Denegre J, Schneider M, Sussman CR, Sunde L, Lildballe DL, Hertz JM, Cornell RA, Murray SA, Manak JR (September 2017). "A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans". Genetics. 207 (1): 215–228. doi:10.1534/genetics.117.1125. PMC 5586373. PMID 28739660.
- Online Mendelian Inheritance in Man (OMIM): 191830
- Rosenblum S, Pal A, Reidy K (April 2017). "Renal development in the fetus and premature infant". Seminars in Fetal & Neonatal Medicine. 22 (2): 58–66. doi:10.1016/j.siny.2017.01.001. PMC 5387761. PMID 28161315.
- Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ (February 2008). "Renal aplasia in humans is associated with RET mutations". American Journal of Human Genetics. 82 (2): 344–51. doi:10.1016/j.ajhg.2007.10.008. PMC 2427293. PMID 18252215.
- Jeanpierre C, Macé G, Parisot M, Morinière V, Pawtowsky A, Benabou M, et al. (July 2011). "RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects" (PDF). Journal of Medical Genetics. 48 (7): 497–504. doi:10.1136/jmg.2010.088526. PMID 21490379. Archived (PDF) from the original on 2019-05-03. Retrieved 2019-06-30.