In this episode of the Better Edge Podcast, Aneesha Shetty, MD, MPH, assistant professor of Medicine in the Division of Nephrology and Hypertension, discusses finding from a recent case report published in the Journal of the American Society of Nephrology.
This study highlights an emerging COVID-19 related kidney disease that is characterized by podocytopathy and/or collapsing FSGS. In investigating this phenomenon among six patients with proteinuria collapsing FSGS and COVID-19 infection, it was observed that the patients were all of recent African ancestry. This led to further investigation into whether this kidney disease is associated with the high risk APOL1 genotype. This association may help predict how a patient will do with COVID-19, their needs after infection recovers, and sheds light on APOL1 genotypes and kidney disease.
COVID-19 Associated Glomerular Disease
Featured Speaker:
Aneesha Shetty, MD
Aneesha Shetty, MD is an Assistant Professor of Medicine (Nephrology and Hypertension) and Surgery (Organ Transplantation). Transcription:
COVID-19 Associated Glomerular Disease
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and joining me today is Dr. Aneesha Shetty. She's an Assistant Professor of Medicine in the Division of Nephrology and Hypertension at Northwestern Medicine. Dr. Shetty recently coauthored a study published in the Journal of the American Society of Nephrology, which highlights an emerging and common COVID-19-related kidney disease that's characterized by podocytopathy and tubular injury.
Dr. Shetty, thank you so much for joining us. In your study, you examined patients of recent African ancestry who developed COVID-19-associated acute kidney injury. Can you give us a brief overview of this study?
Dr Aneesha Shetty: Hi, Melanie. Thank you for having me. We stumbled upon this research question during the initial aspect of the COVID pandemic around March, April. And we had a few patients who were admitted with COVID-19 who had a PCR test that was positive for SARS-CoV-2 that were presenting with kidney injuries, so elevated creatine, lower kidney function. And when we checked their urine, they had a lot of proteinuria, so spilling protein in the urine, which was new for them. And it was different from the then described COVID-associated kidney injury, which was usually seen in patients who were sick in the ICU with very low blood pressures and who didn't have a lot of protein in the urine. So this felt like a different entity.
We started following these patients. We did some extra blood and urine testing on them. They all got kidney biopsies to determine where the proteinuria was coming from. And all the biopsies showed evidence of either podocytopathy or collapsing glomerulonephritis or collapsing FSGS.
Collapsing FSGS is a particular type of FSGS that is seen sometimes in viral illnesses. The very classic collapsing FSGS was seen with HIV when it was first discovered in the '80s and '90s. And the picture of that we were seeing in these COVID-positive patients that we were studying seemed similar to what you would see in an HIV-associated collapsing FSGS. So that really piqued our interest.
We studied six of these patients. Three of them got genetic testing as well that we found an interesting correlation with. And eventually we wrote it up. Now, we're in the process of studying more such patients.
Melanie: That's fascinating, Dr. Shetty. So previous research has demonstrated that there was an association between high-risk gene variants. Can you tell us why this is so significant as it relates to your new study?
Dr Aneesha Shetty: So the six patients that we studied in this phenomenon with proteinuria, collapsing FSGS and COVID-19 infection, they were all of recent African ancestry. One of the thought processes that leads to is whether their kidney disease is associated with an APOL1 gene mutation that is seen in patients with recent African ancestry.
Three out of those six patients consented to genetic testing. So we did a genotyping using their serum. And then one of those three patients was a transplant recipient, so we also did separate genotyping on the tissue biopsy of the transplant kidney, which would be from their donor. All three patients showed a high-risk APOL1 genotype, which has been associated with collapsing FSGS in the past. This is a new finding. This was not described before. There are occasional case reports that were coming out at the time. So ours was one of the bigger studies that showed this association between a high-risk APOL1 genotype and collapsing FSGS in the setting of SARS-CoV-2 infection.
Melanie: So your study also showed that kidney disease didn't necessarily correlate with the severity of respiratory symptoms and there was little evidence of a cytokine storm. Can you tell us more about this?
Dr Aneesha Shetty: That was definitely one of the other interesting aspects of our study. All six of our patients were mostly requiring care on a regular medicine floor. One of them required ICU care for just a day or two. None of them needed intubation or respiratory ventilation. None of them were sick or needed any support for their blood pressures. They were all what you would call milder version of hospital illness and yet their kidney disease was kind of their predominant issue.
One of the thought processes we had was maybe the kidney is acting as a sink for the virus and all its negative effects, all the inflammation and in a way, sparing the rest of the body, in particular the lungs from the cytokine storm that we were seeing in other patients who are sicker.
Melanie: Kidneys are doing a lot of work there. So, three patients underwent genetic analysis and were found to carry high-risk APOL1 genotypes. Though these are really small numbers, doctor, why is this important?
Dr Aneesha Shetty: These are small numbers, but this is an association that really hadn't been described before. And this is very important because it can help predict how a patient may do in the setting of a SARS-CoV-2 infection. it can help prognosticate how these patients do after the infection recovers, what would be the remanent kidney dysfunction that they would have to live long-term with, what would be their risk of complete kidney failure needing either dialysis or transplant.
And it sheds a lot more light also in the world of APOL1 genotypes and kidney disease, which is something that we are studying a lot more now in nephrology. One of the unique findings that we had in our study was there was a discordance in the APOL1 genotype between the one transplant recipient that we had and the donor kidney genotype.
In the APOL1 world, one of the theories of how APOL1 genotypes affects kidney function is that the APOL1 gene codes for a particular protein and that leads to some dysfunction within the kidney itself. So it's sort of a kidney intrinsic pathophysiology. However, what we found was in our transplant patient, the genotype from the blood of the transplant patient was APOL1 high-risk, but the genotype from the transplant kidney itself, which is from the donor, was APOL1 low-risk. So that prompted us to hypothesize that maybe there is more to APOL1 and kidney disease than just kidney intrinsic issues. It's possible that there some things systemic in the body that is seen in patients who are APOL1 high-risk genotype that is also affecting the kidney as opposed to what the thought process has been right now. So we think this is an important hypothesis that needs to be studied further.
Melanie: So given that COVID infections are continuing, is there an urgency to identify specific therapies to protect the kidneys for patients at risk? Tell us about some of the therapies that you're considering.
Dr Aneesha Shetty: Absolutely. I couldn't state that more strongly. Most of the studies that have been done in COVID- specific therapies, specifically the ones we've done earlier with Remdesivir, for example, many of them excluded patients with advanced kidney dysfunction, which made it very difficult to treat patients who came in with kidney injury in the setting of COVID. Now more and more, people are looking into this phenomenon, but it is very important to consider therapies that are particularly relevant for patients with COVID and kidney dysfunction and not just COVID and respiratory disease or stroke or heart disease.
Some examples of therapies that we are using in these patients are we are now using Remdesivir in these patients with kidney dysfunction, we're using dexamethazone in these patients as well. And then, there's thoughts about thinking about monoclonal antibodies in these patients, even considering other types of antibodies, specific tests and a big question is vaccination. What do you do with vaccination? And for now our recommendation is that anybody with kidney dysfunction, no matter what the kidney function may be, what the GFR may be, and even if they are transplant recipients, they should all be recommended to get the vaccine because the thought is it will be protective even for them.
Melanie: That's great information, Dr. Shetty. So what else would you like physicians and scientists to know about this fascinating study as it relates to COVID-19 right now? And while you're telling us that, are you planning to perform additional studies to determine the incidence of proteinuria or a decline in kidney function? Kind of give us a summary and wrap it up and what you would like other providers to take away from your studies.
Dr Aneesha Shetty: That's a really important question. I'm going to answer your second question first. Yes, we are in the process of doing additional studies. We are studying more patients in the same vein, patients who have COVID-19 infection and are having kidney injury and proteinuria. We're doing more biopsies and genotyping, and we're also looking into their cytokine profile.
We're also doing a collaborative study with physician group in Nigeria that is looking at the same cohort of patients with COVID-19 and kidney injury with the idea that the predominance of APOL1 high-risk genotypes may be higher in Nigeria. So we may be able to get more patients who fit this particular profile and be able to understand this association more.
And then Northwestern has a COVID follow-up clinic that is multi-disciplinary that is involving all the specialties that would be involved in a patient's care. So pulmonary, nephrology, cardiology, transplant, infectious disease of course, neurology and that is another source of future studies we're planning on following these patients long-term because the reality is nobody knows what recovery is going to look like. Nobody knows what a patient who had COVID-19 in 2020 is going to feel in 2030. So that's something that we're geared towards trying to study, the long-term effects.
If I were to suggest two take-home points for physicians and scientists from the study that's being be published, take-home point number one is please screen for proteinuria, kidney disease in these patients, no matter how mild their COVID-19 illness is, is one of the lessons we learned that you don't need to be sick. We don't even need to be in the hospital. You could have very mild illness, but have pretty significant kidney injury, so doing a simple urine analysis and a urine protein quantification would be enough to pick it up.
The second lesson we learned was to screen for genotyping in patients with African ancestry who have proteinuria COVID kidney disease. And that is something that has to be done in an institution with the appropriate consent, of course, but it is an important phenomenon to study. And the more we about it, the better we will able to serve and treat these patients.
Melanie: Dr. Shetty, thank you so much. What a fascinating interview and fascinating study. Please join us again to update us as you continue your studies. Thank you again.
To refer your patient or for more information, please visit our website at NM.org to get connected with one of our providers. And that concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.
COVID-19 Associated Glomerular Disease
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and joining me today is Dr. Aneesha Shetty. She's an Assistant Professor of Medicine in the Division of Nephrology and Hypertension at Northwestern Medicine. Dr. Shetty recently coauthored a study published in the Journal of the American Society of Nephrology, which highlights an emerging and common COVID-19-related kidney disease that's characterized by podocytopathy and tubular injury.
Dr. Shetty, thank you so much for joining us. In your study, you examined patients of recent African ancestry who developed COVID-19-associated acute kidney injury. Can you give us a brief overview of this study?
Dr Aneesha Shetty: Hi, Melanie. Thank you for having me. We stumbled upon this research question during the initial aspect of the COVID pandemic around March, April. And we had a few patients who were admitted with COVID-19 who had a PCR test that was positive for SARS-CoV-2 that were presenting with kidney injuries, so elevated creatine, lower kidney function. And when we checked their urine, they had a lot of proteinuria, so spilling protein in the urine, which was new for them. And it was different from the then described COVID-associated kidney injury, which was usually seen in patients who were sick in the ICU with very low blood pressures and who didn't have a lot of protein in the urine. So this felt like a different entity.
We started following these patients. We did some extra blood and urine testing on them. They all got kidney biopsies to determine where the proteinuria was coming from. And all the biopsies showed evidence of either podocytopathy or collapsing glomerulonephritis or collapsing FSGS.
Collapsing FSGS is a particular type of FSGS that is seen sometimes in viral illnesses. The very classic collapsing FSGS was seen with HIV when it was first discovered in the '80s and '90s. And the picture of that we were seeing in these COVID-positive patients that we were studying seemed similar to what you would see in an HIV-associated collapsing FSGS. So that really piqued our interest.
We studied six of these patients. Three of them got genetic testing as well that we found an interesting correlation with. And eventually we wrote it up. Now, we're in the process of studying more such patients.
Melanie: That's fascinating, Dr. Shetty. So previous research has demonstrated that there was an association between high-risk gene variants. Can you tell us why this is so significant as it relates to your new study?
Dr Aneesha Shetty: So the six patients that we studied in this phenomenon with proteinuria, collapsing FSGS and COVID-19 infection, they were all of recent African ancestry. One of the thought processes that leads to is whether their kidney disease is associated with an APOL1 gene mutation that is seen in patients with recent African ancestry.
Three out of those six patients consented to genetic testing. So we did a genotyping using their serum. And then one of those three patients was a transplant recipient, so we also did separate genotyping on the tissue biopsy of the transplant kidney, which would be from their donor. All three patients showed a high-risk APOL1 genotype, which has been associated with collapsing FSGS in the past. This is a new finding. This was not described before. There are occasional case reports that were coming out at the time. So ours was one of the bigger studies that showed this association between a high-risk APOL1 genotype and collapsing FSGS in the setting of SARS-CoV-2 infection.
Melanie: So your study also showed that kidney disease didn't necessarily correlate with the severity of respiratory symptoms and there was little evidence of a cytokine storm. Can you tell us more about this?
Dr Aneesha Shetty: That was definitely one of the other interesting aspects of our study. All six of our patients were mostly requiring care on a regular medicine floor. One of them required ICU care for just a day or two. None of them needed intubation or respiratory ventilation. None of them were sick or needed any support for their blood pressures. They were all what you would call milder version of hospital illness and yet their kidney disease was kind of their predominant issue.
One of the thought processes we had was maybe the kidney is acting as a sink for the virus and all its negative effects, all the inflammation and in a way, sparing the rest of the body, in particular the lungs from the cytokine storm that we were seeing in other patients who are sicker.
Melanie: Kidneys are doing a lot of work there. So, three patients underwent genetic analysis and were found to carry high-risk APOL1 genotypes. Though these are really small numbers, doctor, why is this important?
Dr Aneesha Shetty: These are small numbers, but this is an association that really hadn't been described before. And this is very important because it can help predict how a patient may do in the setting of a SARS-CoV-2 infection. it can help prognosticate how these patients do after the infection recovers, what would be the remanent kidney dysfunction that they would have to live long-term with, what would be their risk of complete kidney failure needing either dialysis or transplant.
And it sheds a lot more light also in the world of APOL1 genotypes and kidney disease, which is something that we are studying a lot more now in nephrology. One of the unique findings that we had in our study was there was a discordance in the APOL1 genotype between the one transplant recipient that we had and the donor kidney genotype.
In the APOL1 world, one of the theories of how APOL1 genotypes affects kidney function is that the APOL1 gene codes for a particular protein and that leads to some dysfunction within the kidney itself. So it's sort of a kidney intrinsic pathophysiology. However, what we found was in our transplant patient, the genotype from the blood of the transplant patient was APOL1 high-risk, but the genotype from the transplant kidney itself, which is from the donor, was APOL1 low-risk. So that prompted us to hypothesize that maybe there is more to APOL1 and kidney disease than just kidney intrinsic issues. It's possible that there some things systemic in the body that is seen in patients who are APOL1 high-risk genotype that is also affecting the kidney as opposed to what the thought process has been right now. So we think this is an important hypothesis that needs to be studied further.
Melanie: So given that COVID infections are continuing, is there an urgency to identify specific therapies to protect the kidneys for patients at risk? Tell us about some of the therapies that you're considering.
Dr Aneesha Shetty: Absolutely. I couldn't state that more strongly. Most of the studies that have been done in COVID- specific therapies, specifically the ones we've done earlier with Remdesivir, for example, many of them excluded patients with advanced kidney dysfunction, which made it very difficult to treat patients who came in with kidney injury in the setting of COVID. Now more and more, people are looking into this phenomenon, but it is very important to consider therapies that are particularly relevant for patients with COVID and kidney dysfunction and not just COVID and respiratory disease or stroke or heart disease.
Some examples of therapies that we are using in these patients are we are now using Remdesivir in these patients with kidney dysfunction, we're using dexamethazone in these patients as well. And then, there's thoughts about thinking about monoclonal antibodies in these patients, even considering other types of antibodies, specific tests and a big question is vaccination. What do you do with vaccination? And for now our recommendation is that anybody with kidney dysfunction, no matter what the kidney function may be, what the GFR may be, and even if they are transplant recipients, they should all be recommended to get the vaccine because the thought is it will be protective even for them.
Melanie: That's great information, Dr. Shetty. So what else would you like physicians and scientists to know about this fascinating study as it relates to COVID-19 right now? And while you're telling us that, are you planning to perform additional studies to determine the incidence of proteinuria or a decline in kidney function? Kind of give us a summary and wrap it up and what you would like other providers to take away from your studies.
Dr Aneesha Shetty: That's a really important question. I'm going to answer your second question first. Yes, we are in the process of doing additional studies. We are studying more patients in the same vein, patients who have COVID-19 infection and are having kidney injury and proteinuria. We're doing more biopsies and genotyping, and we're also looking into their cytokine profile.
We're also doing a collaborative study with physician group in Nigeria that is looking at the same cohort of patients with COVID-19 and kidney injury with the idea that the predominance of APOL1 high-risk genotypes may be higher in Nigeria. So we may be able to get more patients who fit this particular profile and be able to understand this association more.
And then Northwestern has a COVID follow-up clinic that is multi-disciplinary that is involving all the specialties that would be involved in a patient's care. So pulmonary, nephrology, cardiology, transplant, infectious disease of course, neurology and that is another source of future studies we're planning on following these patients long-term because the reality is nobody knows what recovery is going to look like. Nobody knows what a patient who had COVID-19 in 2020 is going to feel in 2030. So that's something that we're geared towards trying to study, the long-term effects.
If I were to suggest two take-home points for physicians and scientists from the study that's being be published, take-home point number one is please screen for proteinuria, kidney disease in these patients, no matter how mild their COVID-19 illness is, is one of the lessons we learned that you don't need to be sick. We don't even need to be in the hospital. You could have very mild illness, but have pretty significant kidney injury, so doing a simple urine analysis and a urine protein quantification would be enough to pick it up.
The second lesson we learned was to screen for genotyping in patients with African ancestry who have proteinuria COVID kidney disease. And that is something that has to be done in an institution with the appropriate consent, of course, but it is an important phenomenon to study. And the more we about it, the better we will able to serve and treat these patients.
Melanie: Dr. Shetty, thank you so much. What a fascinating interview and fascinating study. Please join us again to update us as you continue your studies. Thank you again.
To refer your patient or for more information, please visit our website at NM.org to get connected with one of our providers. And that concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.