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Acute Kidney Injury and COVID-19
Anand Srivastava MD, MPH, discusses a recent study he co-authored, which explores AKI treated with renal replacement therapy in critically ill patients with COVID-19. Although AKI is an important sequela of COVID-19, data on AKI treated with RRT (AKI-RRT) in patients with COVID-19 are limited. This multi-center cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units at 67 hospitals across the United States identified several patient-and hospital-level risk factors for AKI-RRT and death. AKI-RRT is common among critically ill patients with COVID-19 and is associated with high mortality and persistent RRT dependence.
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Learn more about Anand Srivastava, MD, MPH
Anand Srivastava, MD, MPH
Anand Srivastava, MD, MPH is an Assistant Professor of Medicine in the Division of Nephrology and Hypertension at Northwestern Medicine.Learn more about Anand Srivastava, MD, MPH
Transcription:
Acute Kidney Injury and COVID-19
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and joining me today is Dr. Anand Srivastava. He's an assistant professor of medicine in the Division of Nephrology and Hypertension at Northwestern Medicine. He's joining me today to discuss findings from his recent study, which explores acute kidney injury treated with renal replacement therapy in critically ill patients with COVID-19.
Dr. Srivastava, thank you so much for joining us today. Acute kidney injury is emerging as an important sequella of COVID-19. Tell us a little bit more about that and how often it's observed and how important is early recognition as crucial to provide supportive treatment and limit further insults.
Dr Anand Srivastava: Thank you very much, Melanie, for the opportunity to be here today and speak about this topic. So early on in the pandemic, reports from China suggested that the incidence of acute kidney injury or AKI were relatively low, closer to approximately 5%. Since patients with COVID-19 have a heightened inflammatory state often considered a cytokine storm that often requires hospitalization or the need for critical care, many of us in the community believe that this rate was probably low.
Once COVID-19 reached the United States and groups started to collect data on these patients, studies from large healthcare systems such as in New York City identified that the incidence of AKI was nearly 50%. We also saw that the presentations of AKI may be slightly different than the traditional forms of AKI from sepsis since we also saw that patients often had blood and protein in their urine.
Some of the mechanisms proposed to account for the high rates of AKI observed in patients with COVID-19 include ischemic acute tubular necrosis, the cytokine storm that I mentioned, podocytopathies related to the viral illness, medications used to treat the underlying illness that may have nephrotoxic potential or a combination of these etiologies.
Also the mortality rate of patients who have AKI and are hospitalized with COVID-19 was closer to 35%. However, much of this data includes all stages of AKI, including those that are less severe. And there was limited data on the severest form of AKI, individuals who require renal replacement therapy or the need for dialysis, which was really part of the impetus for why we wanted to perform this study.
Melanie: Wow. That's absolutely fascinating. So tell us a little bit about your study. How was it conducted? What happened?
Dr Anand Srivastava: Sure, absolutely. So much of the data that was discussed thus far were either from single center or regional reports and more granular and representative data from across the United States was needed. I served as a site principal investigator here at Northwestern University of the STOP COVID study, which stands for the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19. The main principal investigators are colleagues from the Brigham and Women's Hospital, Dr. Shruti Gupta and Dr. David Leaf.
The study is a multi-center cohort study of critically ill patients with COVID-19 admitted to the intensive care units across the United States. The cohort now includes over 5,000 patients at 68 hospitals with over 400 study investigators and all of the data were manually extracted from the patient's medical records. This amounted to greater than 800 data elements per patient.
In this study, we included nearly 3,100 adult patients with laboratory confirmed COVID-19 admitted to ICUs across 67 hospitals from March 4th to April 11, 2020. The patients were followed until the first of hospital discharge, death, or August 1st, 2020. We excluded patients who already had end-stage kidney disease requiring dialysis. But through this detailed data collection, we collected both patient level and hospital level data to identify risk factors associated with AKI requiring renal replacement therapy within 14 days of ICU admission and risk factors with death at 28 days among individuals who required renal replacement therapy and who had AKI.
Melanie: Wow. Well, that just really got to my next question. So what did you observe for some of the predictors of the 28-day mortality in patients with AKI RRT?
Dr Anand Srivastava: In patients who required RRT, the mortality rate was over 60%. And risk factors for 28-day mortality in the patients who had AKI RRT included older age, severe oliguria, which is lower urine output, and admission to an ICU with fewer ICU beds and/or an ICU with greater regional density of COVID-19.
Melanie: So what are we learning? Tell us about the conclusions of this study.
Dr Anand Srivastava: Well, in this study, we identified that more than one in five critically ill patients developed AKI RRT and whom over 60% died. And among those with AKI RRT who survived to hospital discharge, nearly one in three remained dialysis dependent. We were also able to identify several patient and hospital-level risk factors associated with adverse clinical outcomes. Some of which were previously known based on prior studies of AKI and critical illness and others that were not as well described. And we still need future studies to further identify the long-term outcomes in these patients.
Melanie: Well, then take us from research to patient bed. How can you translate these findings into potential treatment strategies and kind of add to the promising pharmacologic approaches that are being developed, tested in clinical trials? Where do you see this going?
Dr Anand Srivastava: Absolutely. I think that's a really key question. So as is true with other diseases that result in critical illness, AKI is a serious complication that results in a high mortality rate. Particularly when case counts of COVID-19 are high, the rates of AKI can be high as well, which may lead to difficulties in resource allocation. Therefore, open communication with your nephrologist is critical to promptly identify patients who may require renal replacement therapy.
And lastly, patients who survived a critical illness, many of them still require dialysis. Therefore. using these types of hospital-level and patient-level risk factors are needed to better identify those at high risk for AKI RRT, so that we can roll them into clinical trials for novel therapeutics.
Melanie: Doctor, as we're talking about patient level risk factors, I'm just curious, how did the clinical characteristics resource utilization you just mentioned hospital long-term outcomes differ from what you've seen with COVID patients from different trajectories of AKI?
Dr Anand Srivastava: So in this study, we first identify that the AKI RRT incidence was almost 21% within 14 days of ICU admission. And the patient risk factors included a prior history of chronic kidney disease, male sex, nonwhite race, the prior history of hypertension, diabetes, higher body mass index, a higher D- dimer level and greater hypoxemia on ICU admission.
So with some of the risk factors, such as chronic kidney disease, body mass index and hypoxemia, we saw a stepwise relationship between worst levels of these risk factors and AKI RRT. Now some of these risk factors are known from prior studies as well. But there were others that we saw who were further elucidated through the use of this study and those were risk factors where there's a higher body mass index and higher D-dimer level and greater hypoxemia on ICU admission.
Melanie: Just more things we're learning about this mysterious virus. So before we wrap up, what else would you like other physicians to know about your study as it relates to COVID that may help to manage their patients?
Dr Anand Srivastava: I think as we discussed previously, what's really important is understanding what some of these risk factors may be and understanding that AKI is a serious complication that results in high mortality rate. And often patients have difficulty grappling with this, them and their family members. And therefore, open communication with your nephrologist is paramount to identify patients who may require renal replacement therapy or adequate resource allocation, but also being able to have discussions with patients and their families to further understand what some of the complications may be of COVID-19 and what may be needed in the future to monitor for recovery of their kidney function.
Thank you so much, doctor. I hope you'll come back on. Join us again and update us as you continue your studies. Thank you again. To refer your patient, please visit our website at nm.org/nephrology to get connected with one of our providers. 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.
Acute Kidney Injury and COVID-19
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and joining me today is Dr. Anand Srivastava. He's an assistant professor of medicine in the Division of Nephrology and Hypertension at Northwestern Medicine. He's joining me today to discuss findings from his recent study, which explores acute kidney injury treated with renal replacement therapy in critically ill patients with COVID-19.
Dr. Srivastava, thank you so much for joining us today. Acute kidney injury is emerging as an important sequella of COVID-19. Tell us a little bit more about that and how often it's observed and how important is early recognition as crucial to provide supportive treatment and limit further insults.
Dr Anand Srivastava: Thank you very much, Melanie, for the opportunity to be here today and speak about this topic. So early on in the pandemic, reports from China suggested that the incidence of acute kidney injury or AKI were relatively low, closer to approximately 5%. Since patients with COVID-19 have a heightened inflammatory state often considered a cytokine storm that often requires hospitalization or the need for critical care, many of us in the community believe that this rate was probably low.
Once COVID-19 reached the United States and groups started to collect data on these patients, studies from large healthcare systems such as in New York City identified that the incidence of AKI was nearly 50%. We also saw that the presentations of AKI may be slightly different than the traditional forms of AKI from sepsis since we also saw that patients often had blood and protein in their urine.
Some of the mechanisms proposed to account for the high rates of AKI observed in patients with COVID-19 include ischemic acute tubular necrosis, the cytokine storm that I mentioned, podocytopathies related to the viral illness, medications used to treat the underlying illness that may have nephrotoxic potential or a combination of these etiologies.
Also the mortality rate of patients who have AKI and are hospitalized with COVID-19 was closer to 35%. However, much of this data includes all stages of AKI, including those that are less severe. And there was limited data on the severest form of AKI, individuals who require renal replacement therapy or the need for dialysis, which was really part of the impetus for why we wanted to perform this study.
Melanie: Wow. That's absolutely fascinating. So tell us a little bit about your study. How was it conducted? What happened?
Dr Anand Srivastava: Sure, absolutely. So much of the data that was discussed thus far were either from single center or regional reports and more granular and representative data from across the United States was needed. I served as a site principal investigator here at Northwestern University of the STOP COVID study, which stands for the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19. The main principal investigators are colleagues from the Brigham and Women's Hospital, Dr. Shruti Gupta and Dr. David Leaf.
The study is a multi-center cohort study of critically ill patients with COVID-19 admitted to the intensive care units across the United States. The cohort now includes over 5,000 patients at 68 hospitals with over 400 study investigators and all of the data were manually extracted from the patient's medical records. This amounted to greater than 800 data elements per patient.
In this study, we included nearly 3,100 adult patients with laboratory confirmed COVID-19 admitted to ICUs across 67 hospitals from March 4th to April 11, 2020. The patients were followed until the first of hospital discharge, death, or August 1st, 2020. We excluded patients who already had end-stage kidney disease requiring dialysis. But through this detailed data collection, we collected both patient level and hospital level data to identify risk factors associated with AKI requiring renal replacement therapy within 14 days of ICU admission and risk factors with death at 28 days among individuals who required renal replacement therapy and who had AKI.
Melanie: Wow. Well, that just really got to my next question. So what did you observe for some of the predictors of the 28-day mortality in patients with AKI RRT?
Dr Anand Srivastava: In patients who required RRT, the mortality rate was over 60%. And risk factors for 28-day mortality in the patients who had AKI RRT included older age, severe oliguria, which is lower urine output, and admission to an ICU with fewer ICU beds and/or an ICU with greater regional density of COVID-19.
Melanie: So what are we learning? Tell us about the conclusions of this study.
Dr Anand Srivastava: Well, in this study, we identified that more than one in five critically ill patients developed AKI RRT and whom over 60% died. And among those with AKI RRT who survived to hospital discharge, nearly one in three remained dialysis dependent. We were also able to identify several patient and hospital-level risk factors associated with adverse clinical outcomes. Some of which were previously known based on prior studies of AKI and critical illness and others that were not as well described. And we still need future studies to further identify the long-term outcomes in these patients.
Melanie: Well, then take us from research to patient bed. How can you translate these findings into potential treatment strategies and kind of add to the promising pharmacologic approaches that are being developed, tested in clinical trials? Where do you see this going?
Dr Anand Srivastava: Absolutely. I think that's a really key question. So as is true with other diseases that result in critical illness, AKI is a serious complication that results in a high mortality rate. Particularly when case counts of COVID-19 are high, the rates of AKI can be high as well, which may lead to difficulties in resource allocation. Therefore, open communication with your nephrologist is critical to promptly identify patients who may require renal replacement therapy.
And lastly, patients who survived a critical illness, many of them still require dialysis. Therefore. using these types of hospital-level and patient-level risk factors are needed to better identify those at high risk for AKI RRT, so that we can roll them into clinical trials for novel therapeutics.
Melanie: Doctor, as we're talking about patient level risk factors, I'm just curious, how did the clinical characteristics resource utilization you just mentioned hospital long-term outcomes differ from what you've seen with COVID patients from different trajectories of AKI?
Dr Anand Srivastava: So in this study, we first identify that the AKI RRT incidence was almost 21% within 14 days of ICU admission. And the patient risk factors included a prior history of chronic kidney disease, male sex, nonwhite race, the prior history of hypertension, diabetes, higher body mass index, a higher D- dimer level and greater hypoxemia on ICU admission.
So with some of the risk factors, such as chronic kidney disease, body mass index and hypoxemia, we saw a stepwise relationship between worst levels of these risk factors and AKI RRT. Now some of these risk factors are known from prior studies as well. But there were others that we saw who were further elucidated through the use of this study and those were risk factors where there's a higher body mass index and higher D-dimer level and greater hypoxemia on ICU admission.
Melanie: Just more things we're learning about this mysterious virus. So before we wrap up, what else would you like other physicians to know about your study as it relates to COVID that may help to manage their patients?
Dr Anand Srivastava: I think as we discussed previously, what's really important is understanding what some of these risk factors may be and understanding that AKI is a serious complication that results in high mortality rate. And often patients have difficulty grappling with this, them and their family members. And therefore, open communication with your nephrologist is paramount to identify patients who may require renal replacement therapy or adequate resource allocation, but also being able to have discussions with patients and their families to further understand what some of the complications may be of COVID-19 and what may be needed in the future to monitor for recovery of their kidney function.
Thank you so much, doctor. I hope you'll come back on. Join us again and update us as you continue your studies. Thank you again. To refer your patient, please visit our website at nm.org/nephrology to get connected with one of our providers. 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.