Knowledge is Power
The more known about the cause of a person’s disease, the better equipped we are to potentially delay or treat disease as it progresses. Genetic kidney research has advanced significantly in the last decade with new genes associated with kidney disease being identified.
By means of a single blood or spit test, we leverage the latest DNA sequencing technology to test for alternation in DNA in genes known to cause kidney disease
Less than a decade ago there were about 300-400 genes associated with kidney disease and now there are over 600. Using this approach, we find a genetic cause of kidney disease in about one-third of individuals we see in clinic.
As of yet, there are no formal guidelines but if you have a certain type of kidney disease, certain clinical features such as other family members with kidney disease or if following full clinical assessment, you don’t know the cause of your kidney disease, you may benefit from a genetic assessment. More recently it is suggested that if you have a negative or inconclusive genetic result but your healthcare provider suspects a genetic cause for your kidney disease, that you undergo reanalysis every 2 to 3 years. Reanalysis allows for incorporation of new information that becomes available over time into your genetic analysis which can sometimes figure out the cause of your kidney disease.
If we can understand the genetic factors at play in your family’s kidney disease, we can develop a care routine personalized for you – and keep you updated on new therapies and treatment options available now and as they emerge.
It is important to remember that not everyone needs genetic testing. If you have a family history of kidney disease, if the cause of your kidney disease is unclear, if you developed kidney disease at a young age, and if you developed kidney failure before the age of 50, you may benefit from getting tested.
Advantages of Genetic Testing
Confirm or rule out a suspected genetic disease and eliminate uncertainly about your kidney health- Identify what is causing yours or your family’s kidney disease
- Allow for early intervention to potentially prevent or mitigate the onset of kidney disease
- Develop a personalized treatment plan that incorporates the most appropriate medicines or treatments for your specific disease
- Benefit from new medications and treatments as they become available
- Assist with family planning decisions
- Learn from and receive support of other patients with the same or similar conditions
- Personal empowerment associated with finally knowing the true cause of your disease.
Definite guidelines have not yet been established to answer the question of who with kidney disease should undergo genetic testing, but work is ongoing.
Before Getting Tested
Overall, undergoing genetic testing can provide valuable information about your health and help you make informed decisions about your healthcare.
However, it’s important to discuss the risks and benefits of genetic testing with a healthcare professional and to understand the limitations of the test. It’s important to note that genetic testing is not appropriate for everyone.
Additionally, the results of genetic testing may not always provide a definitive diagnosis or predict the course of the disease, as many factors can influence how a particular genetic mutation affects an individual.
If you are undergoing genetic testing, there are several things you should know:
Risks and Benefits of the Test
Genetic testing can provide valuable information about your health, but it also has potential risks, such as the psychological impact of receiving information about your risk of developing a particular condition. It’s important to discuss the risks and benefits of genetic testing with a healthcare professional before undergoing the test.
Accuracy of the Test
Genetic testing is not always 100% accurate, and false positives and false negatives can occur. It’s important to understand the limitations of the test and what the results mean.
Confidentiality
Genetic testing involves sensitive information about your health and genetic makeup. It’s important to understand who will have access to the test results and how the information will be used.
Follow-up Care
If you receive a positive result from genetic testing, you may need to undergo additional testing or monitoring, or make changes to your lifestyle or healthcare plan. It’s important to discuss any necessary follow-up care with a healthcare professional.
We understand in the importance of education and outreach and providing patients with the information and resources they need to make informed decisions about their kidney health and genetic testing options.
Types of Genetic Kidney Disease
Our lab is currently working with patients with all causes of genetics kidney disease. GeneReviews is an international point-of-care resource which provides clinically relevant and medically actionable information for inherited or genetic conditions covering diagnosis, management, and genetic counseling for patients and their families.
Some of the most common genetic kidney disease we diagnose include:
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)
ADTKD is a group of genetic disorders, each of which cause progressive decline in kidney function because of a specific gene mutation. All types of ADTKD have an autosomal dominant inheritance. This means that one of your parents had a mutated gene causing chronic kidney disease and passed it on to you. If a parent has the disease, there is a 50% chance they will pass it on to a child. Impaired kidney function may appear in the teenage years, although the age when kidney failure occurs is highly variable, usually between the ages of 20 and 70 years. They usually do not develop any symptoms until the disease is very advanced. Two genetic conditions account for most cases of ADTKD:
Mucin-1 Kidney Disease, ADTKD-MUC1 or MKD
This type of disease is caused by a mutation in the MUC1 gene which makes the protein mucin-1. It accounts for approximately 30% of ADTKD and lacks distinguishing characteristics other than kidney failure.
Uromodulin Kidney Disease, ADTKD-UMOD or UKD
UKD is caused by a mutation in the UMOD gene which makes the protein uromodulin. This is the most common subtype of ADTKD. Many individuals with UKD also experience gout.
Congenital Anomalies of the Kidney and Urinary Tract
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a group of kidney disorders that result in changes or defects in the number, size, shape, structure or function of the kidney and/or genitourinary tract. As they are usually present from birth, they are considered congenital and are the most common cause of kidney failure before the age of 30 years. Although present from birth, many individuals may be unaware that they have CAKUT as many cases are asymptomatic. For example, if an individual is born with one kidney, they may not know about it until they have a scan performed for another reason. Some individuals with reflux may present earlier due to recurrent kidney infections. It is estimated that 10-15% of cases of CAKUT are genetic in origin.
CKD of Unknown Cause
Chronic Kidney Disease of unknown cause (CKDu) is the term used to describe the situation where after undergoing a full medical assessment and testing (which may include a kidney biopsy), the cause of kidney disease remains unclear. It is estimated that anywhere between 10-30% of all individuals with kidney disease may have an unknown cause of kidney disease. Chronic kidney disease is largely a silent disease which means that patients may not seek medical attention until they have advanced kidney disease. In these cases, the kidneys may be small due to chronic scarring and in these cases a kidney biopsy is not possible. If a kidney biopsy is performed often the only finding is chronic scarring of the kidney which cannot reveal the cause of damage to the kidney. In families who have kidney disease of unknown causes, research has now shown that genetic testing can in some cases be helpful in finally determining the initial cause of disease.
Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities
ZMYM2 is a gene that when mutated results is a clinical spectrum termed Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities. Mutations in this gene were first described Dr Connaughton and Dr Hilderbrandt in patients with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). This group identified in 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Since then, several other individuals have discovered they carry mutations in this gene. There is ongoing research work aiming to better understand exactly how this disease occurs.
Link to paper: Am J Hum Genet. 2020 Oct 1;107(4):727-742. Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations PMID 32891193
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