Genetics, Cyst Formation, and Inheritance Patterns of Polycystic Kidney Disease

Exon Publications, Brisbane, Australia


Polycystic Kidney Disease (PKD) is a genetic disorder characterized by the formation of numerous cysts in the kidneys. This chapter explores the genetic mutations, cyst formation, molecular mechanisms of cyst formation, inheritance patterns, and the role of genetic testing and counseling for PKD. ADPKD (Autosomal Dominant Polycystic Kidney Disease) and ARPKD (Autosomal Recessive Polycystic Kidney Disease) are the two main types of PKD, each caused by mutations in different genes and inherited in different ways. Understanding the molecular pathways affected by these mutations, such as cAMP signaling and mTOR pathways, helps in comprehending how the disease progresses. Genetic testing can confirm a diagnosis of PKD, while genetic counseling provides crucial support and information for individuals and families.

Keywords: Genetic counseling for polycystic kidney disease; Genetic testing benefits for PKD; Inheritance patterns of PKD; Molecular pathways in polycystic kidney disease; Mutations in PKD1 and PKD2 genes; Pathways involved in PKD cyst formation; Polycystic kidney disease gene therapy research; Role of calcium signaling in PKD; Understanding cAMP pathway in PKD; Vasopressin pathway in polycystic kidney disease

Correspondence: Exon Publications, Brisbane, Australia. books@exonpublications.com

Cite as: Genetics, Cyst Formation, and Inheritance Patterns of Polycystic Kidney Disease. In: Polycystic Kidney Disease: Public Education. Brisbane (AU): Exon Publications; 2024. Online first 2024 May 28. ISBN: 978-0-6458663-8-4.

Doi: https://doi.org/10.36255/polycystic-kidney-disease-genetics-cyst-formation-inheritance

Copyright: Exon Publications.

License: This article is published under Attribution-NonCommercial-NoDerivatives license (BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/


Polycystic Kidney Disease (PKD) affects millions of people worldwide and is one of the most common genetic disorders. It is characterized by the growth of numerous cysts in the kidneys, which can lead to kidney enlargement and loss of function. PKD is primarily caused by genetic mutations that disrupt normal kidney cell functions. Understanding the genetic basis of PKD, including the specific mutations and inheritance patterns, is crucial for diagnosis and management. Additionally, knowledge of the molecular pathways involved in PKD, such as the cAMP signaling and mTOR pathways, provides insights into how the disease progresses. Genetic testing and counseling play vital roles in diagnosing PKD, understanding its implications, and providing support to affected individuals and their families. This chapter aims to present these aspects in an accessible way, helping readers understand the genetic and molecular foundations of PKD and the importance of genetic testing and counseling (111).


PKD is a genetic condition, which means it is caused by changes in our DNA. Our DNA contains genes, which are like instruction manuals for our bodies, telling them how to grow and function. In PKD, certain genes have mutations, or changes, that cause problems in the kidneys. There are two main types of PKD, each caused by different genetic mutations: Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Autosomal Recessive Polycystic Kidney Disease (ARPKD). The genes responsible for ADPKD are PKD1 and PKD2. The gene responsible for ARPKD is called PKHD1. Mutations in these genes cause the formation of cysts in the kidneys and sometimes in other organs as well. PKD1 mutations are more common and tend to cause more severe disease than PKD2 mutations.


The PKD1 gene produces a protein called polycystin-1, while the PKD2 gene produces polycystin-2. These two proteins work together and are found on the surface of kidney cells. They are part of a structure called the primary cilium, which acts like an antenna on the cell surface, sensing mechanical and chemical signals from the environment. This sensing is important for maintaining the normal function and structure of the kidney.

When there is a mutation in either PKD1 or PKD2, the polycystin proteins do not function properly. This disrupts the signaling pathways that control cell growth, division, and the formation of cysts. As a result, the cells start to behave abnormally, leading to the growth of fluid-filled cysts. These cysts can grow and multiply over time, causing the kidneys to enlarge and lose their ability to function properly.

The PKHD1 gene, which is involved in ARPKD, produces a protein called fibrocystin. Like polycystin-1 and polycystin-2, fibrocystin is also involved in the function of the primary cilium. Mutations in the PKHD1 gene lead to defects in fibrocystin, which also disrupts normal cellular signaling and leads to cyst formation.

As these cells continue to grow and divide abnormally, they start to form small sacs filled with fluid. These sacs are the early cysts. Over time, these cysts can grow larger and larger. One of the reasons they grow is because of an increase in fluid secretion into the cysts. The cells lining the cysts pump fluid into the sacs, causing them to expand. This fluid is not the same as urine; it is a different kind of liquid that builds up inside the cysts.

As cysts grow, they compress the surrounding kidney tissue, leading to further damage and loss of kidney function. This is why PKD is a progressive disease, meaning it gets worse over time. The growing cysts not only impair the kidneys' ability to filter waste from the blood but can also cause pain and other complications.

Molecular pathways are involved in cyst formation

Several key pathways in the cells contribute to this process. One important pathway is the cyclic AMP (cAMP) signaling pathway. In healthy cells, cAMP helps regulate various functions, including fluid balance. In PKD, the levels of cAMP are abnormally high, which promotes fluid secretion into the cysts and stimulates further cell growth. This is why targeting the cAMP pathway is a focus for developing new treatments for PKD.

Another important pathway is the mTOR pathway. This pathway regulates cell growth, proliferation, and survival. In PKD, the mTOR pathway becomes overactive, further contributing to the growth and expansion of cysts. Inhibitors of the mTOR pathway are being studied as potential treatments to slow down cyst growth.

Calcium signaling also plays a crucial role in cyst formation. Polycystin-1 and polycystin-2 help regulate calcium levels inside the cells. When these proteins are not working properly, calcium signaling is disrupted, which contributes to abnormal cell growth and cyst formation.

Inflammation and oxidative stress are additional factors that promote cyst growth in PKD. The abnormal cellular environment in the kidneys leads to chronic inflammation, which can damage kidney tissue and promote the expansion of cysts. Oxidative stress, caused by an excess of harmful molecules called free radicals, further exacerbates this process.


ADPKD is the most common form of PKD. In this type, if one parent has ADPKD, there is a 50% chance that the child will inherit the disease. This is because ADPKD is caused by a mutation in one of two genes, PKD1 or PKD2, and only one copy of the mutated gene is needed to cause the disease. If a parent has the mutated gene, they have a 50% chance of passing it on to each child, regardless of gender. This pattern is called "autosomal dominant" because the gene responsible for the disease is located on one of the autosomes (non-sex chromosomes) and only one copy of the mutated gene is necessary for the disease to occur.

In families where ADPKD is present, multiple generations are often affected, meaning that grandparents, parents, and children can all have the disease. Because of this, ADPKD is sometimes called a "familial" disease.

ARPKD is much rarer than ADPKD and follows a different pattern of inheritance. For a child to inherit ARPKD, both parents must carry a copy of the mutated gene, even though they may not show any symptoms of the disease themselves. When both parents are carriers, there is a 25% chance that the child will inherit two copies of the mutated gene (one from each parent) and develop the disease. There is a 50% chance that the child will inherit only one copy of the mutated gene and become a carrier like the parents, without developing symptoms. Finally, there is a 25% chance that the child will inherit two normal copies of the gene and neither develop the disease nor be a carrier.

This pattern is called "autosomal recessive" because the gene responsible for the disease is located on one of the autosomes and two copies of the mutated gene (one from each parent) are necessary for the disease to occur. ARPKD typically presents symptoms in infancy or early childhood and can cause serious health problems at a young age.


Understanding the inheritance patterns of PKD is crucial for affected families. Depending on your condition, your doctor may refer you for genetic testing and genetic counseling. Genetic testing is a process that looks for specific changes or mutations in a person's DNA. For PKD, this means looking for mutations in the PKD1, PKD2, and PKHD1 genes.

There are different types of genetic tests available for PKD. The most common ones are blood tests or saliva tests, where a sample is taken and sent to a laboratory for analysis. The lab examines the DNA in the sample to check for mutations in the PKD genes. This testing can be done at any age, and it is especially useful for people who have a family history of PKD and want to know if they have inherited the condition.

Genetic counseling is a service that helps individuals and families understand the results of genetic tests. A genetic counselor is a healthcare professional with specialized training in genetics and counseling. They work with people to interpret test results, understand the implications, and provide support.

When you go for genetic counseling, the counselor will review your medical and family history to assess your risk of having or passing on PKD. They will explain the genetic testing process, what the results might mean, and help you decide whether to proceed with testing. If you choose to have genetic testing, the counselor will help you understand the results when they come back.

For individuals with a confirmed diagnosis of PKD, genetic counseling can provide valuable information about the progression of the disease, potential symptoms, and management options. This knowledge can help in planning for regular check-ups, lifestyle adjustments, and treatment choices.

Prenatal testing is another option for expecting mothers who have a family history of PKD. This testing can determine whether the baby has inherited the condition. Tests such as amniocentesis or chorionic villus sampling (CVS) can be performed during pregnancy to analyze the baby's DNA for PKD mutations. These tests carry some risks, and the decision to undergo prenatal testing should be made with careful consideration and guidance from a genetic counselor.


PKD is a complex genetic disorder with significant implications for affected individuals and their families. Understanding the genetic mutations and inheritance patterns of PKD, including the differences between ADPKD and ARPKD, is essential for accurate diagnosis and effective management. The molecular pathways disrupted by these genetic mutations, such as cAMP signaling and mTOR pathways, are critical to understanding how cysts form and grow in the kidneys. Genetic testing provides a definitive diagnosis, while genetic counseling offers invaluable support and information, helping individuals make informed decisions about their health and family planning.


This article is part of our public education series. It was written by professional medical writers for the public using simple terms based on our medical book Polycystic Kidney Disease and articles indexed in PubMed, and further peer-reviewed for factual accuracy by independent experts. It is intended solely for informational purposes and is not to be considered medical advice. The views and opinions expressed in this article are believed to be accurate at the time of publication, but the publisher, editors, or authors cannot be held responsible or liable for any errors, omissions, or consequences arising from the use of the information contained in this article. The publisher makes no warranties, implicit or explicit, regarding the contents of this article or its use.


The copyright of this article belongs to Exon Publications (Publisher). The electronic version is published under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 (BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/. What does this mean? BY: Credit must be given to the Publisher as the original source. NC: Only noncommercial uses of the work are permitted. ND: No derivatives or adaptations of the work are permitted. For commercial purposes, please contact the Publisher.


  1. Li X, Editor. Polycystic Kidney Disease. Brisbane (AU): Exon Publications, 2015. https://doi.org/10.15586/codon.pkd.2015
  2. Harris PC, Rossetti S. Molecular diagnostics for autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2010;6(4):197-206. https://doi.org/10.1038/nrneph.2010.18
  3. Torres VE, Harris PC. Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol. 2014;25(1):18-32.https://doi.org/10.1681/ASN.2013040398
  4. Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2002;13(9):2384-2398. https://doi.org/10.1097/01.ASN.0000028643.17901.42
  5. Ong AC, Harris PC. Molecular pathogenesis of ADPKD: the polycystin complex gets complex. Kidney Int. 2005;67(4):1234-1247. https://doi.org/10.1111/j.1523-1755.2005.00201.x
  6. Wilson PD. Polycystic kidney disease. N Engl J Med. 2004;350(2):151-164. https://doi.org/10.1056/NEJMra022161
  7. Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet. 2019;393(10174):919-935. https://doi.org/10.1016/S0140-6736(18)32782-X
  8. Bergmann C, et al. Polycystic kidney disease. Nat Rev Dis Primers. 2018;4:50. https://doi.org/10.1038/s41572-018-0047-y
  9. Reed B, et al. Variation in age at ESRD in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2008;51(2):173-183. https://doi.org/10.1053/j.ajkd.2007.10.037
  10. Rossetti S, et al. The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol. 2002;13(5):1230-1237. https://doi.org/10.1097/01.ASN.0000013300.11876.37
  11. Chapman AB, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015;88(1):17-27. https://doi.org/10.1038/ki.2015.59