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This episode of Butts & Guts features Dr. Xiangling Wang, a Staff Physician in Cleveland Clinic's Genomic Medicine Institute in the Department of Kidney Medicine. She discusses genetic testing and kidney disease management with the podcast's host, Dr. Scott Steele. Listen and learn more about genetic testing, who should consider having a genetic evaluation for kidney disease, and the type of care you can expect from Dr. Wang and the renal genetics program team at Cleveland Clinic.

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Genetic Testing & Kidney Disease Management

Podcast Transcript

Dr. Scott Steele: Butts & Guts, a Cleveland Clinic podcast exploring your digestive and surgical health from end to end.

Dr. Scott Steele: Hi everyone, and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, the Chair of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. Today we're going to talk about something that we have not talked about a whole lot, and that's genetic testing and kidney disease management. I'm extremely pleased to have Dr. Xiangling Wang, who is a Staff Physician in Cleveland Clinic's Genomic Medicine Institute in the Department of Kidney Medicine. Dr. Wang, thanks so much for joining us here on Butts and Guts.

Dr. Xiangling Wang: Thank you so very much for having me. It's a great pleasure to be here.

Dr. Scott Steele: We always like to start out with you telling us a little bit about yourself.

Dr. Xiangling Wang: Sure, absolutely. Well, I actually came through a long journey. I did my medical training in China and actually practiced as a nephrologist for about two years in Shanghai before I moved to this beautiful country. After I moved here, I did my training in both clinical and research nephrology. During my research training with Dr. Lieske at the Mayo Clinic on genetic kidney stone disorders, I realized my interest was in genetics. So, I moved forward and completed additional training in medical genetics at the Mayo Clinic. Also, I finished my training in clinical nephrology in the UT Southwestern Medical Center, Dallas, and Loma Linda University. So now, I became one of very few double-trained nephrologists and medical geneticists in this country.

Dr. Scott Steele: Well, we're super glad that you're here at the Cleveland Clinic and all the expertise that you bring. So on this episode, we're going to discuss genetic testing in kidney disease management. To start, can you tell us a little bit about what goes on in Cleveland Clinic's genetic testing program for kidney disease, or renal genetics program?

Dr. Xiangling Wang: Absolutely. We started the renal genetics program in January 2019, which is one of very few programs available in the country, and rarely led by a double-trained nephrologists and medical geneticists. Our team includes nephrologists, the geneticists, and very dedicated renal genetic counselors. Since we started, our patient volume has jumped up tenfold. Before the start of our program we had about 10 renal genetic patients in our genetic clinic per year, and now we have 25 to 30 patients per week.

Dr. Scott Steele: Wow.

Dr. Xiangling Wang: Yeah, we have seen more than 400 patients so far, referred from 15 different specialties, from both internally and externally, with a diagnosis yield of 50%. For those patients with a positive genetic testing result, 60% of patients received a new diagnosis or a change in their diagnosis. And more than 30 patients received a significant change in their management, including initiation or discontinuation of any medications. We have been doing really well, we have received tremendous positive feedback from our patients, their families, and the referring providers. I'm very proud that our renal genetic program received the Caregiver Celebration Excellence Award at Enterprise Level in 2021. We have been doing really good. I'm very excited and proud of our progress of our program.

Dr. Scott Steele: So there's a lot of patients out there that have kidney disease, and I know what genetic testing is. Who should consider having a genetic evaluation for kidney disease?

Dr. Xiangling Wang: That's a great question. Studies should nearly 10% of patients with chronic kidney disease have a genetic disorder. In our clinic, actually, we have seen patients with variable presentations, from glomerular disease presenting with hematuria, proteinuria, to cystic kidney disease, to congenital anomalies of kidneys, urinary tract, to electrolytes, these things like potassium, magnesium, phosphorus, calcium, et cetera, added to kidney stones or calcinosis, which means the calcium deposits in both kidneys. So I would say usually the indications for referral to a renal genetic clinic, the indication is broad. For any patients with chronic kidney disease or unknown etiology, genetics evaluations should be considered, particularly for those with a family history of kidney disease. Our studies have clearly shown that patients with a family history of kidney disease, they are strongly associated with a positive genetic testing result.

Dr. Scott Steele: What does genetic testing process entail? If a patient's going to come in and see you, what can they expect during that visit?

Dr. Xiangling Wang: Sure. Yeah. When a patient comes to our clinic, he or she will see a renal genetic counselor first to collect the history, particularly the three-generation family history. Then the patient will be evaluated by a physician with a physical exam, and then a genetic testing will be decided after the evaluation. So the results will then be wrapped by the team and the patient will receive a pre-test counseling, including the genetic testing pros and cons of the genetic testing, and what the possible result the patient may anticipate. If the patient agrees to proceed with the genetic testing, we will submit insurance pre-authorization. If that is approved, we will initiate the test, and usually the patient will anticipate the result in about three weeks. If we have the positive result, we will possibly schedule a follow-up for the patient to go through the result in detail. We will contact the patient and report the result to them.

Dr. Scott Steele: Just to clarify, that not everybody that you see is actually having an indication to get a genetic testing. A patient may go there with the idea they're going to get that, but after your first evaluation, you may say, "This isn't really warranted in you."

Dr. Xiangling Wang: Yeah, that's true. Yeah. Not all patients, they are indicated for the genetic testing, so a thorough evaluation by an expert in renal genetics is needed. Actually, we have around 10% of patients, we say, "Hey, no, we don't think you need a genetic testing." And some of patients will say, "Well, I really want to confirm." So I am very proud to say, we have a 100% negative predicting rate. When we see you don't have that, all the genetic testing comes back negative.

Dr. Scott Steele: That's fantastic, and that leads right into my next question. How accurate is genetic testing?

Dr. Xiangling Wang: I would say genetic testing is very accurate. If you have a positive genetic testing result, a genetic diagnosis is made. However, I would point out that if the patient has a negative genetic testing result, that does not mean genetic kidney disease is ruled out. That possibly means the patient still has a genetic kidney disease, but that is caused by some new genes that we have not discovered yet. So in this kind of patient, if our clinical suspicion for a genetic disorder is very high, we should continue to follow up the patient, and reanalyze our data, and may do additional testing.

Dr. Scott Steele: That kind of leads right into my next question, so how do you discern these results? And how do these results then influence your approach to either further testing or treatment?

Dr. Xiangling Wang: Sure. In the lab, they follow the guideline of the American College of Medical Genetic and Genomics, and the Association of Molecular Pathology to interpret the genetic awareness. The words are classified into five categories, which include pathogenic, likely pathogenic, variant of unknown significance, likely benign, or benign. So the classification are based on criteria using evidence, including population data, computational data, functional data, and separate patient data. So the testing results often have implications of management.

One example I would like to say is, for one disorder, it's called Focal Segmental Glomerulosclerosis, is a common cause for chronic kidney disease and often being treated with steroids and immunosuppression. However, if the patient is diagnosed with a genetic form of FSGS, they should not be treated with steroids and immunosuppression, because they will not respond to that, but suffer the side effects of that. So when the patient have that positive genetic testing result, they should be discontinued with this treatment.

And besides the immediate change in the management for our patients, the whole family actually benefits from the genetic testing result. I would say the family could benefit from two ways. One is, we will give them an accurate recurrent risk for their children, and all other at-risk family members. And second is that for the presymptomatic or asymptomatic at-risk family members, they can have an early diagnosis using the familial variant test.

Dr. Scott Steele: We talk a lot about genetic testing and the results with the family, like you just talked about. Can you talk a little bit about age? Is there any age limitations to that? Or if somebody comes back positive, should their kids be tested, regardless, even if they're infants or young kids?

Dr. Xiangling Wang: Oh, that's a good question. Yes, patients can have a genetic evaluation at any age. In our clinic, actually, we have some newborn babies, and we have same patients in their eighties or nineties. But also I would like to point out, based on the genetics guideline, usually for the pediatric patients, if for the adult-onset genetic disorder, we usually counsel the family to make sure that they understand the chance of potential discrimination because of the genetic information. We have to make sure the family fully understands the consequence of the genetic testing. Yes, the genetic testing can be offered for patients at any age, but they have to fully understand the potential consequence.

Dr. Scott Steele: You gave one example of a disease, and there's a lot of kidney diseases that are out there. But once early detection of kidney disease genes are found, are there preventative measures that a patient can take place to minimize their risk of developing further disease? Or is that disease-dependent? Is it the glomerulosclerosis nephritis or something? Is that specific, and the other one not? Or how does it all work?

Dr. Xiangling Wang: I would say, generally the answer is yes, also it depends on the disorder. I would say the majority of the patients will benefit from an early diagnosis. The patient with kidney disease, they often benefit from lifestyle and dietary change. One example I would show is for patients with some dominant possibilities of getting kidney disease, there’s a significant benefit from adequate water intake, low sodium diet, limit their caffeine intake, and monitoring of their blood pressure and control. I would say these measures can slow down the progression of their kidney disease, so early diagnosis with genetic testing is very helpful.

Dr. Scott Steele: Truth or myth? Genetic testing is the most accurate method of early detection for kidney disease, truth or myth?

Dr. Xiangling Wang: This is an interesting question. I would say yes, but I would add that it is true if the genetic cause is known in the family. Then we can diagnose patients with familiar variant test, even before they start to present with clinical or laboratory abnormalities such as proteinuria or hematuria. We are not in the stage where we can offer a screening genetic testing for asymptomatic or presymptomatic patients to detect a kidney disease, but obviously, it might be the part of our future practice.

Dr. Scott Steele: Truth or myth? Genetics only play a part of the role in whether someone has kidney disease. Other factors that you mentioned, diet, exercise, can also be a big factor.

Dr. Xiangling Wang: Yes, truth.

Dr. Scott Steele: Truth or myth? The variants of unknown significant typically go on to become a known genetic defect.

Dr. Xiangling Wang: The data in renal genetics is not clear, but from other specialty studies show that upfront certain patients with variant of unknown significance, they will be reclassified, and the majority of them will be downgraded to benign.

Dr. Scott Steele: Great. What's on the horizon for you and your team here in this field of renal genetics?

Dr. Xiangling Wang: Well, renal genetics is a relatively new, but very exciting field. With the new technology and new discovery of a number of new genes related to kidney disease, and more excitingly, gene therapy becoming available in our practice, we really have the opportunity to practice nephrology in a fashion of precision medicine. I, and our team, are very proud to be part of this field. Our team has worked hard with the focus on three major areas.

First, we continue to analyze our own experience in the clinical practice to share with colleagues around the world, to help others build up their own programs. We hope our experience, particularly the diagnostic algorithm, could help guide the practice in renal genetics of others.

Second, we have received philanthropy funding to build up a renal genetics training program. With this program, we aim to train our next-generation nephrologists, geneticists, and genetic counselors, with a focus in renal genetics. We will provide a unique, one-month rotation for trainees nationwide with hands-on experience in diagnosing and managing patients with genetic kidney disease. This unique program will be open to accept applicants this year.

And third, we have been very active in a number of clinical trials of genetic kidney disease, and we will continue to do so. Furthermore, our researchers have been working tirelessly on new gene discovery tactical therapy for patients with genetic kidney disease. Indeed, I'm very excited and proud about the future of this field.

Dr. Scott Steele: That's fantastic stuff. Now it's time for our quick hitters, a chance to get to know you a little bit better. First of all, what is your favorite sport?

Dr. Xiangling Wang: Ah, basketball.

Dr. Scott Steele: Fantastic. Got a favorite team?

Dr. Xiangling Wang: Of course, Cleveland, come on.

Dr. Scott Steele: There we go. What's your favorite meal?

Dr. Xiangling Wang: Ah, that's, I'm a foodie. I love all.

Dr. Scott Steele: That's fantastic. If you had a bucket list of a place that you'd like to travel to, where would that be?

Dr. Xiangling Wang: I’ve always wanted to go back to my hometown, Shandong.

Dr. Scott Steele: Fantastic. And then finally, tell us something, you've obviously lived around the world, something that you like about living here in Northeast Ohio.

Dr. Xiangling Wang: The beautiful full seasons, and colorful change.

Dr. Scott Steele: Fantastic. Me, too. What's the final take-home message for our listeners regarding this field of renal genetics?

Dr. Xiangling Wang: I would say renal genetics is really changing the landscape of nephrology practice, believe it or not. Genetic testing is becoming more accessible and affordable to our patients. All patients with a suspected genetic disorder should have a genetic evaluation for accurate diagnosis and management. Please do not be hesitant to contact us. If you have any questions, our team is here to help you.

Dr. Scott Steele: That's fantastic, and so for more information on Cleveland Clinic's Renal Genetics program, please call 216,636.1768, that's 216.636.1768. You can also visit the website,, that's Dr. Wang, thanks so much for joining us on Butts & Guts.

Dr. Xiangling Wang: Thank you.

Dr. Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.

Butts & Guts

Butts & Guts

A Cleveland Clinic podcast exploring your digestive and surgical health from end to end. You’ll learn how to have the best digestive health possible from your gall bladder to your liver and more from our host, Colorectal Surgery Chairman Scott Steele, MD.
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