Published on June 14, 2022 | With polycystic kidney disease, there is a 50% chance of passing the disease to children. Due to the high chance of passing PKD to future generations, many have questions about genetic testing. To better understand the role of genetic testing in people with ADPKD, we sought advice from an expert.
Neera Dahl, M.D., Ph.D., is the director of the Nephrology Clinical Trials Program at Yale School of Medicine in New Haven, Connecticut. Her expertise is in the diagnosis and management of inherited kidney disease, with a focus on ADPKD and other cystic kidney diseases that mimic ADPKD.
Why is genetic testing important for people with ADPKD?
ADPKD is primarily diagnosed on clinical grounds. When we see a patient who has a family history of the disease and then look at their imaging and see cysts in the kidneys, we typically make the diagnosis. But it may still be important to consider genetic testing because there are other inherited diseases that can cause cysts but that have a very different risk for end-stage kidney disease (ESKD).
For instance, autosomal dominant polycystic liver disease (ADPLD) also causes liver and kidney cysts. But we think the mutations that cause ADPKD (but not ADPLD) are those responsible for the progression to kidney failure. So, genetic testing may be important to provide information about the likely course of the disease.
Are there any other reasons for doing testing?
The other times to look at genetic testing is if someone in the family had a very different disease course than others. For instance, if your parent was in their 70s when they developed ESKD, but you’re 30 and already facing dialysis, then you may benefit from genetic testing to find out what’s behind that. Or if you have liver fibrosis (scarring) rather than cysts, that could be related to a mutation in some other gene besides PKD1 or PKD2, which cause ADPKD.
We also recommend testing for the 10% to 15% of patients with ADPKD who have no known family history. It’s important to make a genetic diagnosis to ensure that we’re dealing with ADPKD and not something that looks like it.
How does genetic testing affect treatment decisions?
Right now, our treatments are based on the risk of progression. Those at highest risk are the ones treated most aggressively and who may benefit from tolvaptan. However, the genetic diagnosis can also be very helpful in assessing the risk of progression based on the specific mutation and some clinical features.
Are there any negatives to doing genetic testing?
Our genetic information is protected by the Genetic Information Nondiscrimination Act. Genetic testing results cannot be used to determine medical insurance costs or availability. However, the law doesn’t protect against discrimination for life or disability insurance, which may require a review of all your medical information.
Is testing being used to tailor treatments?
Yes, and that’s one of the really exciting parts of where the field is going. There are therapies in development that will increase the expression of polycystin-1 or -2 proteins, which are defective or missing in ADPKD. Going forward, we may be doing genotyping (genetic testing) to determine which families will benefit from which therapies.
Where does preimplantation genetic testing come in?
This is something we discuss with all our young patients, because if one parent has ADPKD, they have a 50% chance of having a child with the disease. In preimplantation genetic testing, in vitro fertilization occurs, and before the embryo or embryos are implanted, they’re genetically tested for evidence of ADPKD. Those embryos without the genetic mutation are implanted. This allows the couple the opportunity to feel they’re doing everything they can to prevent the disease in the next generation.
Want to see more articles like this? Read the full issue of our magazine, PKD Life, and subscribe to future issues here. Also, be sure to register for PKDCON 2022 to attend Dr. Dahl’s session, “Understanding Polycystic Liver Disease.”
Hi, I had genetic testing as I have PKD with no family history. I’m in my 40’s watching my kidney function decline. Mine came back negative. My doctor said that 10% come back negative but I probably still have ADPKD based on my clinical presentation. I’ve tried to research other disease that causes PKD but can’t find anything apart from the liver disease you mention but my liver is not involved. So I’m guessing there is a 10% error in genetic testing, giving false negatives. Is this correct? I feel that the genetic testing didn’t give me any answers, in fact I’m more unsure now as prior to testing it was presumed ADPKD and now it’s still just presumed I guess, especially with no family history.
Hi Emma! Actually, a small portion (10%) of people diagnosed with ADPKD have no family history of the disease, with the disease developing as a spontaneous (new) mutation.
You can learn more about what causes ADPKD here: https://pkdcure.org/what-is-adpkd/what-causes-adpkd/
Emma, have you had an abdominal ultrasound? My case of ADPKD was diagnosed after my primary care doctor was doing my annual internal exam and felt something peculiar, so she ordered an ultrasound. I turned out I had cysts on both kidneys and also some liver cysts. I notified my siblings and my brother also was diagnosed with ADPKD. I was 50 when I found out and it was about 13 or14 years later I started dialysis. I did dialysis for 4 years before I was fortunate to get a living donor kidney transplant. My brother also did dialysis and 3 years later had a transplant. I had genetic testing done for the breast cancer genes (which was negative) since both my mother and sister had breast cancer. We assume it was my father who had carried the PKD gene, although he never knew it and died young from a final heart attack.
Thanks Christine, yes I’ve had an ultrasound and they said both my kidneys have so many cysts there were too many to count. So I guess with so many cysts ADPKD is probably correct even without family history and no identified gene. Thank you for sharing your story
Emma, I’m 56 w/ unclear family history of PKD. I was diagnosed in 2000 & now have very large cystic kidneys. Just got my genetic results & was also negative. Dr told me there are still unidentified mutations so I guess we’re in the same club. I was hoping to get my son tested but without a specific gene to look for, results are not guaranteed. I am doing another round of more specific gene tests. Ask your dr about doing this. Good luck!
what this means is that one of your parents is not your real parent. that is the 10% right there.
there has to be a family history hence why it does not skip generations. one parent has only to be the carrier not both , so if u have ADPKD and both “known” parents each dont have it , conclusiin , one of your parents is not really yours ,
If you have ADPKD and you receive Chemotherapy for Colon Cancer how does that impact your ADPKD progression?
Unfortunately, we do not have a resource that addresses Chemotherapy and PKD. We highly recommend that you contact your health care provider to ensure you get the right information for your specific situation.
I am a 38 year old female with a mother and brother with PKD. I’ve had several kidney ultrasounds and no cysts found. My family doctor says I probably would have had cysts by now if I had pkd. My question is I have done ivf and we are looking at doing an embryo transfer. The clinic has suggested we do genetic testing (which I heard requires 3 pkd family members testing). They say we can then do genetic testing on the embryos to determine which have pkd. This will take many months and is also costly. I was also told by the imaging tech based on my ultrasound I do not have pkd.
Is it pretty safe to rule out pkd by age almost 39 no cysts or symptoms? I haven’t been able to find much definitive info on this. I’m just torn with whether to looking into the genetic testing route before our embryo transfer as I don’t want to pass on.
Hi, please, I would like some help. Why do some ADPKD experts not suggest preimplantation evaluation with in vitro fertilization for couples with one of the affected partners? Are there major technical difficulties regarding this technique related to the genes of this disease? What are the success/failure rates of these procedures, and what are the rates of gene transmission even performing the preimplantation analysis? Thanks.
Hi there, please keep in mind that we can not give out specific medical advice. We highly recommend you connect with your healthcare provider so you receive the most accurate information. Thank you.
How do you get the insurance to cover ADpKD genetic testing? Only 1 of 3 daughters might qualify as a living donor but cannot start anything without a genetic test first. She’s 26 now and told anyone under 30 must have genetic testing done.
What is the specific name of the test for PKD that shows if you are recessive or dominant?