Episode 5: COVID-19 and Acute Kidney Injury:  What We Know Today and Potential Long-Term Impacts with Dr. Ted Toffelmire
As the COVID-19 pandemic continues, its impacts on the body continue to be understood. Dr. Ted Toffelmire, the Senior Director of Medical Affairs in Canada for Fresenius Medical Care North America, joins Field Notes to discuss a potential link between the devastating virus and acute kidney injury.

Brad Puffer: Welcome everyone to this episode of Field Notes. I'm Brad Puffer on the medical office communications team at Fresenius Medical Care North America, and your host for this discussion today. Here, we interview the experts, researchers, physicians, and caregivers who bring experience, compassion, and insight into the work we do every day.

There is mounting evidence that COVID-19, not only damages the lungs, but also the kidneys, often resulting in emergency dialysis. A recent study by the Feinstein Institute for Medical Research suggests that more than a third of patients hospitalized for COVID-19 suffered kidney damage in New York City. The study published in Kidney International also suggests that patients with respiratory failure were more likely to develop acute kidney injury with almost 15% of those patients requiring emergency dialysis.

In response to this crisis, Fresenius Medical Care rush dialysis machines and supplies into hospitals across the US to meet this demand along with dialysis nurses who travel to support the hardest hit areas. Despite this major health issue, fewer than one in five Americans know that COVID-19 can cause renal damage according to a survey conducted in June by the National Kidney Foundation. So we all have a lot to learn.

That's why we want to dive deeper into this important issue today with one of our company's leading nephrologists. Dr. Ted Toffelmire is the senior director of medical affairs in Canada for Fresenius Medical Care in North America. He has spent the last several months, looking closely at all the research that are showing the impact of COVID-19 on the kidneys. Dr. Toffelmire, welcome to Field Notes.

Dr. Ted Toffelmire: Thank you very much, Brad. It's my pleasure to be here. I'm looking forward to our chat.

Brad Puffer: First, for anybody listening who may not be a nephrologist, what exactly is acute kidney injury and how is it different than what most people think about as kidney disease?

Dr. Ted Toffelmire: That's an interesting question because it could take a couple of books to go over, but the short answer is that what most people hear about with kidney disease, patients being on dialysis, et cetera is what we call chronic kidney disease. It's kidney disease where the kidneys have suffered irreparable damage and permanently will not get better again. Acute kidney injury is a completely different animal.

And from a kidney perspective or from a physician perspective, we really hope to be able to detect acute kidney injury early on in its course because it's synonymous with could be improved, could recover almost totally. So somebody with acute kidney injury may be able to recover their injury and get back almost to normal kidney function.

And with that in mind, how quickly does that happen? It may happen within minutes or hours or possibly days, possibly up to a week and if we can detect it in that period of time, hopefully, we can treat it to prevent it from getting any worse.

Brad Puffer: So instead of a disease that's taking time to develop and finally, the kidneys are not functioning anymore, this could be something that happens suddenly. It could be an accident, for example, or it could be a disease like COVID-19.

Dr. Ted Toffelmire: That's exactly it. It might be an accident where the kidney injury happens in a period of minutes or it could be a drug or a poison or a disease process like this, which may cause kidney injury gradually over a period of days, which hopefully, we can detect and then allow recovery.

Brad Puffer: So when it comes to COVID-19, then what do we now know about how significantly this coronavirus is impacting the kidneys? And how big a concern is this?

Dr. Ted Toffelmire: Yeah, that's a tough question and I got to say it's tough because we only have six months experience with this virus. A certain amount of what we know about this virus is based on what we knew about SARS and MERS from 10, 20 years ago.

And certainly, we've learned lots of the last six months about what coronavirus can do with the kidneys. And I guess, it's for that reason that much of the data that we can see in the literature or on the news can be quite variable. It's only because we've only had six months of experience with it.

The short answer is that coronavirus can certainly damage kidneys. It appears that it can damage kidneys possibly directly by the virus invading the kidney and more often and more commonly, just by the disease process in the body itself causing a major inflammatory process, which then causes basically collateral damage in the kidney, which causes the acute kidney injury.

Brad Puffer: So it sounds like there's possibly two things going on here. You're talking about the disease causing multi-organ failure, which impacts the kidneys but you also mentioned that the virus could be actually attacking the kidneys themselves. How would that happen? How does that work?

Dr. Ted Toffelmire: That's certainly an area that nephrologists are particularly interested in. And we get down into the molecular levels and at this point, we don't have firm evidence that the virus actually causes damage within the kidney but we are certainly collecting pieces of the jigsaw puzzle that look like the picture is going to be put together in that direction.

What happens is that the virus itself like other coronaviruses have a spike on the outside of the virus, which is then recognized by some of the cells in our body. This spike protein is recognized by the protein in our body called ACE2, which stands for angiotensin-converting enzyme number 2. And some of the cells in our body that have lots of that enzyme on the outside of it-- lots of that protein on the inside it can be found in our nose or our throat, a little bit in our lungs, certainly in our brain and our nerves. And some on our kidney and some on our muscles.

So when that virus finds a cell with this ACE2 on the outside of it, that virus spike and the cell ACE2 then come together. And that allows the virus to then be sucked into or enveloped into the cell. Once that virus is inside the cell, for example, inside the kidney cell, that virus can then take over the metabolic machinery in that cell and develop, create new viruses, new copies of itself.

And then, put those copies into the blood to make the infection worse. Obviously, when it does that, that cell can no longer function as it was designed to function. So one would think that if that's happening in the kidney, then some of the kidney cells which are designed to get rid of poisons and toxins from our blood, concentrate urine, get rid of urine-- that sort of thing. Some of those cells may then not work as they were designed to function. If it's acute kidney injury that we might be able to reverse that.

Brad Puffer: Well, sounds like we still have a lot to learn, but really interesting to think about just how this virus is going after the kidneys potentially. My understanding is that a lot of nephrologists were surprised by just how much acute kidney injury was happening in New York City, for example. So are some people more susceptible to AKI resulting from COVID-19 than others? Why would there be such a dramatic difference in some areas of the world to others?

Dr. Ted Toffelmire: Yeah, Brad. That's a hard question. And the reason is because none of us expected a high degree of acute kidney injury from COVID-19 because other coronaviruses that have infected humans have had a relatively low impact on kidneys even though they've had a similar spike protein that has resulted in the infection.

Certainly, part of the issue is the type of health care, the health care systems, for example. Italy had a high degree of kidney disease and I think that largely that was related to the fact that their health care system really was overrun. I'm not sure about the numbers in China, whether they were overrun or whether they address the patients very quickly.

We certainly get into the genetics of the patients. And the reason why genetics rises is because the ACE2 protein is on our X chromosomes. So we each have a little bit of a different ACE2 protein.

Females have two different ACE2 proteins in general. One for each of the X chromosomes. Males have one. And so one of the questions is, are males getting sicker, are males dying faster with COVID because they've got only one X chromosome, one type of ACE2 rather than the females.

Certainly, there's genetic differences with these two around the world. And we're certainly looking into whether the COVID-19 virus has better attachment to some of those ACE2's than others. But we don't have evidence to support that just yet. We're certainly looking into it very carefully.

The virus also is changing. It's evolved since it was first seen in December. So that it has a number of different mutations on it.

And one of the thoughts now is that maybe this evolved newer virus is more susceptible, more efficacious at causing damage within kidneys or within human cells. So come back to me in six months. We'll probably have more information on along this line as to whether there's genetic susceptibility, whether there's ethnic changes, whether there's differences across the nations.

Brad Puffer: Well, for those people who end up at the hospital with COVID and then, also progressed to acute kidney injury, how are we treating those patients? And what are the best options for patients?

Dr. Ted Toffelmire: This goes back to the basics of medical care. So a physician, when they see a patient, we'll certainly be keeping an eye on their kidneys and certainly because we know COVID-19 can affect kidneys. We certainly watch for any type of kidney abnormality, kidney damage, deterioration of kidney function.

And when we're looking for that, if we see some deterioration, if we can see that there's acute kidney injury going on, then the very first thing that we do regardless of the disease is try to figure out what the cause of the acute kidney injury is in this specific patient, in this specific instance. And even in the patients with COVID-19, there are a variety of different reasons why they might have kidney injury.

Some of the patients in New York were found to be quite dehydrated when they first came to the hospital. And so the dehydration could be a cause of the kidney injury. Some of the medications that we're giving them may cause some deterioration in kidney function.

So the first job of the nephrologist at the bedside or the physician at the bedside is to identify what the cause or potential causes of the acute kidney injury is. And then, remove those causes so if the patient's dehydrated, give them some fluid, either intravenously or to drink. If it's a medication that they're taking, then take away that medication.

If it's because of the inflammatory response to the disease itself, then the best option there is to treat the disease itself. Try to reduce the inflammation. Try to control the disease. And when you put each of these different factors into place to try to treat the acute kidney injury, the hope is at the end that the kidneys will be damaged only slightly and will be able to recover after the disease process has taken its course.

Brad Puffer: And for those who do develop kidney failure in which the kidneys are so injured that they're no longer able to even produce urine or their function is drastically reduced. My understanding is dialysis and a wide variety of different techniques have been used based on the demand in order to meet the needs of these patients. Correct?

Dr. Ted Toffelmire: You're quite right that there's a wide variety of different types of dialysis that is being given to these patients. And honestly, it's not because one is any better than the other. It's because our systems around the world are stretched so much that any type of dialysis will do the trick.

In some places, nurses would prefer to use a dialysis machine that has a remote control on it. So the patient can be 15 or 20 feet away from the nurse. In other situations because the space is tight, it would be nicer to have a small machine that is compact. And you can take care of the patient like that. Those, for example, are the NxStage machines that you're referring to having gone into New York City.

In other cases, some patients find that they do better if the dialysis occurs over a prolonged period of time. And this prolonged period of time, honestly, depends on what equipment is available-- can the prolonged period of time be over 8 hours or 12 hours or 24 hours-- and whichever machine you have available. You can do it over that sort of longer period of time.

So once a patient has dialysis, I have to emphasize that in this situation or when dialysis is given for acute kidney injury that does not mean that we've all sudden gone into chronic kidney injury with irreversible prognosis. But rather the purpose of giving dialysis to patients with acute kidney injury is to tie them over until a certain amount of their kidney function can recover. And the hope is that the kidneys will recover to a certain extent, hopefully, to the point where they can come off of dialysis.

Unfortunately, this isn't often the case with many types of kidney injury. But I've just learned of some recent data out of the United States where a number of these patients are improving after they've been discharged from the hospital on dialysis. After they've been on dialysis for a period of time, some of them, the kidneys have recovered even after that period of time. So that they have been able to stop dialysis at least temporarily.

Brad Puffer: That's great news. Certainly, great to hear. There may be some people listening who are concerned about the long-term impact of COVID-19 on the kidneys even if there is not acute kidney injury. I know there's a lot of speculation here. But is there any concerns about lingering or long-term damage that might have even not be seen right now or is it just too early to know?

Dr. Ted Toffelmire: Oh, it's way too early to know. What you're asking really is-- and this applies not only to the kidneys, but to the brain, to the nerves, to the heart, to the muscles. What's the long-term effect of COVID-19 infection on a patient. How will they work? How would their bodies work physiologically after a year or two after the disease?

And we have to wait a year or two to be actually able to see that, but certainly, initial suggestions, hypotheses are that these organs may have suffered a certain amount of permanent damage. Even though the patients have recovered kidney function after coming off of dialysis, there may well be some permanent damage there. But we would need to be able to follow them for a period of months or years to be able to see the outcome of that, whether or not there can be complete recovery or not.

Dr. Ted Toffelmire: Well, Dr. Toffelmire, as I mentioned earlier, you're based in Canada, still part of Fresenius Medical Care North America. And certain regions of the world have been responding differently depending on the health care systems. But what has your experience been in trying to address this crisis in Canada and has it helped being part of the Fresenius Medical Care ecosystem that is really global?

Dr. Ted Toffelmire: Certainly from the perspective of a scientist or a clinician, we don't have a border in mind. We don't have politics in mind. We look at our colleagues around the world and try to see what they did best and they always get in touch with us and direct us as to the best potential that we can provide the best care that we can provide.

I've been impressed with the Fresenius Medical Care global office. Right from the first, there was wide open communication around the regions. We had calls on a weekly basis at first to speak with all of the leaders in each of the areas, covering all of what their learnings were, all of what they were suggesting to avoid all that sort of thing.

It, then, came to devices. Certainly, in Canada, the preparation across Canada was to have major centers get a good supply of ventilators of Novalung for ECMO of dialysis machines, both acute and chronic of water systems. Certainly, within Fresenius, those requests were not anticipated last year or the year before. So there was a lot of effort within Fresenius Canada to see where we could fill those requests of our colleagues in the community.

And it was nice to be part of the Fresenius family in that we could easily reach out to Europe, reach out to the United States, reach out to Asia. And quite frankly, reach out to our regulators in the states to FDA and Canada to help Canada to try to get machines and devices that are available elsewhere into our center, both Canada and the United States, so that they can be used and that's happened in both of our countries.

Brad Puffer: It has been impressive to see that response. And I'm glad you touched upon that, because it certainly took a lot of coordination, collaboration, and work to get to this point and to be able to respond the way the company has.

Dr. Ted Toffelmire: The response goes further than just clinical care at the bedside. The biggest help, the biggest armamentarium that we have as clinicians and scientists to treat this disease is information and knowledge. And one of the first things that the global medical office put into place was one location where all of this all of our information could be accessed and could be seen by everybody within the company. And that's yet another example of, basically, moving mountains to achieve something that was beneficial at the bedside at the time.

Brad Puffer: That's a great point Dr. Toffelmire. And it's been really exciting to see that collaboration and work in order to respond not just in the US, but in Canada, where you are across the globe. It's been a complete pleasure speaking with you, Dr. Toffelmire. Thank you so much for taking the time.

Dr. Ted Toffelmire: It's my pleasure, Brad.

Brad Puffer: And to our audience you can find Field Notes on the Apple Store or Google Play or right here at fmcna.com. Or you can also find our annual medical report and other feature articles. We hope you'll come back and join us as we discuss more important issues in the weeks ahead.

Until next time. I'm Brad Puffer. And you've been listening to Field Notes by Fresenius Medical Care. Take care everyone.