5 Questions with Dr. Gefen

Summary

Blood, Sweat and Smears: 5 Questions with Dr. Ashley Geffen

Podcast: Blood, Sweat and Smears – A Machaon Diagnostics Podcast
Air Date: August 5, 2024
Host: Bjorn (standing in for Dr. Brad Lewis)
Guest: Dr. Ashley Geffen, Pediatric Nephrologist, Phoenix Children’s

---

Episode Overview

This episode features pediatric nephrologist Dr. Ashley Geffen, who responds to "Five Questions" about diseases at the intersection of nephrology and hematology, especially those involving complement dysregulation and rare kidney disorders. The conversation covers disease differentiation, the challenges of diagnosing and treating pediatric cases, the future of genetic testing, and advice for aspiring pediatric nephrologists.

---

Key Discussion Points and Insights

1. Comparing C3G and HUS

• Bjorn’s Question: “I once heard C3G described as a HUS, confined to the kidneys. To what extent is that description correct or off the mark?”
• Dr. Geffen’s Insight [01:43]:
  • The analogy is “mostly... off the mark.”
  • Commonality: Both involve complement dysregulation.
  • Key Distinction:
    • On biopsy, they look “totally different.”
    • C3GN is marked by C3 deposition in the kidneys.
    • HUS presents as a thrombotic microangiopathy.
  • Quote:

    “Even though they're both closely related to complement, they look totally different. … The kidney presentation is totally different.” — Dr. Geffen [01:59]

  • Genetics may overlap due to complement dysregulation, but the clinical manifestations and pathology differ greatly.

---

2. Acquired TTP in Pediatrics

• Bjorn’s Question: “Is it ever acquired TTP in pediatrics?”
• Dr. Geffen’s Insight [02:59]:
  • “Never say never, but... extremely rare.”
  • First consideration in children is almost always HUS.
  • Rare pediatric TTP cases seen are usually genetic/inherited, not acquired.
  • Plasma exchange is considered if presentation is unusual.
  • Quote:

    “Never say never, but highly unlikely from my experience.” — Dr. Geffen [03:28]

---

3. Making the Case for Pediatric Nephrology

• Bjorn’s Question: “How would you market pediatric nephrology to medical students?”
• Dr. Geffen’s Insight [03:48]:
  • If you like kids, pediatrics is fulfilling—“always brings a smile to my face.”
  • Offers tremendous variety: ICU, outpatient, chronic care, and genetics.
  • “The physiology of the kidneys is so complicated and involves so many transporters. And math, if you like math, probably right for you.”
  • Exposure to rare diseases is common—“I see rare disorders pretty much every day.”
  • Emphasizes intrinsic interest, variety, intellectual challenge, and patient connections.
  • Quote:

    “If you like variety, I think that's a great specialty.” — Dr. Geffen [04:49]
    “If you're someone who likes rare conditions… get bored doing the same thing every day, pediatric nephrology would be like a perfect thing for you and highly recommend it.” — Dr. Geffen [05:48]

---

4. Biggest Question Facing Pediatric Nephrology

• Bjorn’s Question: “What is the single biggest question facing pediatric nephrology?”
• Dr. Geffen’s Insight [06:14]:
  • Integration of genetic testing into daily practice.
  • Genetic testing has become more accessible in the last five years.
  • Pediatric nephrologists now have wider access and support for genetic counseling.
  • The ongoing question: How will genetic insights change care and therapy?
  • Potential for developing novel therapies targeting rare genetic kidney diseases.
  • Quote:

    “I really think that's going to make a huge difference over the next five to 10 years as to how we practice, and not only that, but potentially novel therapies for all these rare diseases that we see all the time.” — Dr. Geffen [07:23]

---

5. Most Important Tool When AHUS is on the Differential

• Bjorn’s Question: “When AHUS is on your differential, what is the most important tool in your toolbox?”
• Dr. Geffen’s Insight [07:52]:
  • Genetic testing is invaluable for long-term management and care planning.
  • Treatment decisions (e.g., eculizumab) are not delayed for genetic results.
  • A positive genetic finding informs prognosis: may justify lifelong complement inhibitor therapy.
  • Up to 50% of cases may not have a known variant—patients should be counseled accordingly.
  • Quote:

    “If a patient has genetic testing that clearly shows they have a variant [that] would predispose them to genetic HUS, that's super useful because then I know, okay, these patients are going to need complement inhibitors, likely lifelong.” — Dr. Geffen [08:23]

---

Bonus Question: Recommendation for Listeners

• Travel Recommendation:
  • Dr. Geffen recommends visiting Japan—recently spent a month there, traveling widely including Okinawa and Hokkaido.
  • “Japan is so interesting and such a great place to visit… the food is amazing. The culture is so different… but similar in a lot of ways too.”
  • Quote:

    “If you like to travel, take the opportunity to visit Japan. That would be my one recommendation.” — Dr. Geffen [09:43]

---

Notable Quotes & Memorable Moments

• On the difference between C3GN and HUS:

  “The pathology being so different, you can't really say they're like the same thing confined to the kidney because the kidney presentation is totally different.” — Dr. Geffen [02:16]

• On the appeal of pediatric nephrology:

  “You get a taste of the ICU… you're also sort of a primary care doctor for a lot of these kids, especially with chronic kidney disease… If you like variety, I think that's a great specialty.” — Dr. Geffen [04:20, 04:49]

• On genetic advances:

  “About five years ago, [there was] this sort of boom in genetics in nephrology... how is this going to affect what we do?” — Dr. Geffen [06:35]

---

Timestamps for Key Segments

• C3G vs HUS: 01:43 – 02:52
• Acquired TTP in Pediatrics: 02:52 – 03:34
• Marketing Pediatric Nephrology: 03:48 – 06:05
• Biggest Question Facing the Field: 06:14 – 07:44
• AHUS: Most Important Tool: 07:52 – 09:12
• Bonus Recommendation (Japan): 09:22 – 10:11

---

Summary

Dr. Ashley Geffen articulates both the scientific complexity and personal fulfillment she finds in pediatric nephrology, emphasizing the specialty’s diversity, intellectual excitement, and the dramatic impact emerging genetic tools will have on the diagnosis and management of rare kidney diseases. Her clinical approach is pragmatic and patient-centered—empowering families with information, leveraging genetic testing for long-term planning, and advocating for early and aggressive therapy when needed. Her enthusiasm for her field and life (with a plug for travel in Japan) makes this interview informative and inspiring for both clinicians and students considering this unique subspecialty.

Transcript

[A]

Hello and welcome to Blood, Sweat and Smears, a podcast produced by Macheon Diagnostics. In this podcast series, we will be discussing thrombosis and hemostasis from the perspective of our host benign hematologist and medical director of Macheon Diagnostics, Dr. Brad Lewis. Please remember to subscribe and leave a review. With that, I'll turn it over to Dr. Lewis. Brad, take it away.

[B]

Hi, my name is Bjorn, and I'm sitting in for Dr. Lewis for our series called Five Questions, where we pose five questions to physicians in and around the disease areas we work in. We hope you find these short interviews interesting, and if you don't, that's probably my fault. Today I'm joined by Dr. Ashley Geffen, who is a pediatric nephrologist specializing in genetic kidney diseases, tubular disorders, and kidney stone disease at Phoenix Children's, where, yes, it is hot, but it's a dry heat. Thank you for joining us today, Dr. Geffen.

[C]

Thank you. Yes, I've been spending pretty much all of my time indoors, so honestly haven't noticed the heat too much.

[B]

I looked at the weather today. It was horrifying. It is hot here in California. If you're outside of the bay Today here, it's high 80s, which I know would be an absolute dream for you.

[C]

Well, I used to live in the Bay Area, so I know it was always a little chilly over there.

[B]

So it can be today. Today it's pretty lovely. All right, so we're going to get right into it. Here's our first question. I once heard C3G described as a hus, confined to the kidneys. To what extent is that description correct or off the mark?

[C]

So I think mostly it's off the mark. I think that there is some grain of truth, but basically, I think the main thing that would be in common with them is complement dysregulation. Aside from that, they look totally different on biopsy. They're both related to complement dysregulation, but on biopsy they look totally different. C3GN is really just confined to the kidneys and you see C3 deposition in the kidneys. But then whereas with husband, as you guys well know, it's thrombotic microangiopathy. And so that's the sort of thing that you see on biopsy rather than C3 deposition. So even though they're both closely related to complement, they look totally different. And I think, you know, with the pathology being so different, you can't really say they're like the same thing confined to the kidney because the Kidney presentation is totally different. Could the genetics be related? Because again, the. The complement dysregulation. Totally, definitely. There's some overlap there and sort of background mechanism is similar, but totally different.

[B]

Question number two. Is it ever acquired TTP in pediatrics?

[C]

Never say never, but I think it's extremely rare. My first thought is always HUS in a child, although depending on the presentation, especially if it's a little bit unusual, then I always have to consider ttp. And in those situations, I would definitely do plasma exchange. But most of the time, almost always it's hus. And if it is ttp, the few cases I've seen have been genetic or inherited and not acquired. So never say never, but highly unlikely from my experience.

[B]

Question number three, across a lot of pediatric subspecialties, the number of new physicians is declining. If you were going to give a marketing spiel to convince medical students to consider pediatric nephrology, how might that go?

[C]

Well, first off, I would say that pediatrics is awesome. If you like kids. If you like kids, you're set in pediatrics. Because no matter what, even if you have a bad day, at the end of the day, you're like, oh, I saw these really cute kids. It, you know, it always brings a smile to my face, at least, because I just. I've always just loved kids. So that's one thing about pediatric nephrology, just pediatrics, period. But in terms of nephrology, I'm actually one of those people who's known, they wanted to be a pediatric nephrologist since medical school, which is kind of unusual. But I got to do a rotation really early, and I just fell in love with it. The things that I loved about it then and I still love about it now, are that you see such a wide variety of pathology and also acuity. And in that, you get a taste of the icu. You get to be in the ICU relatively often doing continuous kidney replacement therapy and consults there. But you're also sort of a primary care doctor for a lot of these kids, especially with chronic kidney disease, who you see just in your office, it's very relaxed. It's not the same thing at all as being in the icu. And then there's that middle ground of most pediatric nephrology centers have their own service, and so you get that kind of middle ground. So it's. If you like variety, I think that's a great specialty. But specifically why the kidneys? Well, I also think the pathology of the kidneys is the most Interesting. And of course I'm biased being that I've loved nephrology for a very long time, but the physiology of the kidneys is so complicated and involves so many transporters. And math, if you like math, probably right for you. If not, maybe not your first choice. But the pathology is so interesting, and we see so much genetic disease in pediatric nephrology compared to adult nephrology, where it's mostly hypertension, diabetes. I see rare disorders pretty much every day. And that's one of the things that I absolutely love about pediatric nephrology. So if you're someone who likes rare conditions that are super interesting and have super interesting pathology, get bored doing the same thing every day, pediatric nephrology would be like a perfect thing for you and highly recommend it. I've loved it so far.

[B]

Great. That leads right into question four, which is, what do you think is the single biggest question facing pediatric nephrology right now?

[C]

Being that my area of interest is genetics, I might be a little bit biased, but I think the biggest question facing pediatric nephrology right now is how do we integrate genetic testing into our daily practice? And how is that going to shape how we practice going into the future? Genetic testing wasn't really very readily available to most people until a few years ago, about five years ago. Before then, you know, you'd have to send testing often to, like, research labs or labs where it would take a very long time to get results. So it's not necessarily something you could take action on immediately. But about five years ago, in this sort of boom in genetics in nephrology, where now pretty much any pediatric nephrologist anywhere in the country, whether or not they're at a big center, can send genetics. And a lot of the places that do these genetics have support. Even if you don't know a whole lot about genetics, you have support from the company to help you with the counseling aspects of it. With it being so widely available, how is this going to affect what we do? I know it affects what I do all the time and every day. But again, I am biased in that this is my sort of favorite part of pediatric nephrology and the thing that I think about the most, but I really think that's going to make a huge difference over the next five to 10 years as to how we practice, and not only that, but potentially novel therapies for all these rare diseases that we see all the time.

[B]

Question number five. When AHUs is on your differential, what is the most Important tool in your toolbox.

[C]

So there's so many of them, so it's a. It's a bit hard to choose. I think again, me being biased in genetics world, I think that the genetic testing is extremely important. Will I wait on genetic testing to treat a patient? No. That it will. It is not my most important thing when I'm deciding do I use eclizumab or not or some sort of terminal complement inhibitor. No, that's not going to be my decision point. But when it comes to long term management of patients, if a patient has genetic testing that clearly shows they have a variant would predispose them to genetic hus, that's super useful because then I know, okay, these patients are going to need complement inhibitors, likely lifelong. If it's negative, though, I always counsel patients about this too. That 50% somewhere around there can have genetic causes of HUS, but we just don't have the answer yet. So if it's negative, it's not necessarily as helpful. But when it's positive, it gives a lot of information for us, for the families too, what, you know, the rest of the child's life is going to look like and again, what kind of medications they're going to need. So for me, that's something that's become extremely invaluable, especially again as genetic tests become more available over the last several years.

[B]

Great. That's our five questions. Now we have our bonus question, which is what is one thing, anything that you'd recommend?

[C]

Well, I am a big traveler. I love going all over the place. I don't know how many countries I've been to at this point, but. But I did spend about a month in Japan this past summer and I absolutely loved it. It was my second time there. But the first time I was there for a short period, this was a whole month where I got to go to Okinawa and go to Hokkaido, like the islands in the north part of the country. I would highly, highly recommend to anyone who likes to travel. Japan is so interesting and such a great place to visit. The food is amazing. The culture is so different from that of America, but similar in a lot of ways too. Actually, I just found it very fascinating. So I would say if you like to travel, take the opportunity to visit Japan. That would be my 1 recommendation.

[B]

Fantastic. That's great. And thank you very much for your time today, Dr. Geffen. And I hope it drops below 100 this week.

[C]

Yes, I will definitely be spending some time in the pool to cool down if I do go outside.

[B]

Fantastic. Take care that's it for us here.

[A]

At Blood, Sweat and Smears, a podcast produced by Matrion Diagnostics, your reference lab and CRO specializing in thrombosis, hemostasis, and rare disease. Thank you for listening, and if you have a question or comment or there's a topic you'd like Dr. Lewis to speak to, please send us an email to blood, sweat and smearsay that's M A C H A O N diagnostics.com youm can follow Macheon at twitteriondx. Be sure to subscribe to Stay in the know. Share this podcast with clinicians you think might appreciate it, and we hope you'll join us next time here at Blood, Sweat and Smears.