Announcer:
Welcome to CME on ReachMD. This activity, entitled “Cases in Acute Kidney Injury: Applications for Clinical Practice” is provided by Prova Education and is supported by an independent educational grant from bioMérieux.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the Learning Objectives.
Dr. Kane-Gill:
Welcome. Our panel today is enthusiastic about discussing this evolving topic of biomarkers for early detection of acute kidney injury. Acute kidney injury, or AKI, is a common complication of patient care occurring in around 10% to 15% of patients admitted to the hospital. This number and prevalence gets even higher in ICU patients at about 50%. Substantial medical intervention is often necessary to achieve maximal outcomes for patients with acute kidney injury. Early detection of patients at high risk for developing AKI is at the heart of improving these outcomes, especially with the emergence of predictive biomarkers. But the question is: How often are biomarkers used, and how should they be used along with other patient clinical data when making medical decisions? Today we will discuss two cases with the goal of answering these questions.
This is CME on ReachMD. I’m Dr. Sandra Kane-Gill.
Dr. Zarbock:
Hi. My name is Alexander Zarbock. I am an anesthesiologist and intensivist, and I’m located in Münster in Germany.
Dr. Pickkers:
Good day. My name is Peter Pickkers. I’m an internist intensivist, and I’m located in the Netherlands.
Dr. Kane-Gill:
So let’s get started. Our first case today is Thomas, a 50-year-old black male with an acute myocardial infarction and a ventricular septal defect. Some pertinent labs include a troponin of 7.16 ng/mL, a creatinine kinase of 470 U/L, and a CK-MB of 40 U/L. His comorbidities include diabetes and atrial fibrillation. He has no known history of kidney disease and has a baseline creatinine of 0.7 mg/dL. During his hospitalization, Thomas underwent a coronary revascularization, closure of his ventricular septal defect, and a transcatheter aortic valve replacement. Thomas had a prolonged phase of hypotension during cardiopulmonary bypass.
Dr. Zarbock, what are your concerns for this patient related to the risk for acute kidney injury, and also, what are the current approaches to monitoring kidney function and the advantages and disadvantages to those monitoring parameters?
Dr. Zarbock:
Thank you very much. So acute kidney injury is a common complication of the cardiac surgery. Nowadays, we use the KDIGO [Kidney Disease: Improving Global Outcomes] criteria to diagnose and stage an AKI, and the definition is based on changes of the serum creatinine and/or urine output. However, those functional biomarkers have several limitations, so the serum creatinine has a low sensitivity, and the urine output has a low specificity.
The new biomarkers, TIMP-2 and IGFBP7, have a very good predictive value, especially after cardiac surgery. The lower cutoff value is 0.3, so patients who have a value greater than 0.3 have an increased risk to develop an acute kidney injury. That means in numbers that more than 70% of the cardiac surgery patients with a value of higher than 0.3 develop an acute kidney injury.
TIMP-2 and IGFBP7 are two molecules that are involved in the cell cycle arrest. Once the cells get damaged or have stress, they enter the cell cycle arrest. The advantage of the markers is that they reflect a kidney stress and not a kidney damage. At this early stage, it is possible to implement supportive measures to optimize the situation, and by implementing such supportive measures at an early stage of kidney stress, it is possible to prevent the development of acute kidney injury.
Dr. Kane-Gill:
Great. So, Dr. Pickkers, Dr. Zarbock has highlighted the limitations of functional biomarkers and also the utility of TIMP-2/IGFBP7 as a stress biomarker of early detection of acute kidney injury. This new biomarker is one of the ones that we use at our institution since it is FDA-approved in the United States. Could you provide some background on the validation process and cutoffs for this test and also how these newer biomarkers have been incorporated into the KDIGO criteria for staging acute kidney injury?
Dr. Pickkers:
Yes, thank you very much. I think the main reason how these biomarkers were approved is twofold. One was the observational studies that show that, indeed, increased levels of the biomarkers were predictive for the development of AKI. So you know it earlier, that AKI will develop, and so that gives you some room to do something in these patients. And a second thing is that Dr. Zarbock himself and his group show that, indeed, if you do secondary prevention measures that are described in KDIGO in a subgroup of patients with a high risk to develop AKI based on a level that is increased of the biomarker, you are able to prevent AKI, so less patients will develop that. So it’s not only that you can know it earlier and that’s it, but you can actually do stuff that prevents the development of AKI. And I think these are the simple measures that are taken.
So we aim, of course, that we do KDIGO guidelines in all patients, but we have to be real that we are not that good at it. But if you focus on the subgroup of patients that you know are at high risk, then you are much better at it. So, indeed, in these patients, you can try to prevent to give them nephrotoxic drugs, you will think of alternatives if they need a contrast CT scan, their hemodynamic management will be more strict, for example, their volume status will be measured, for example, with use of PiCCO, and so you can actually, if you take those measures, prevent AKI.
Another thing that’s really important, I think, that the cutoff value of 0.3 was indeed related to more than 70% of the patients that develop AKI, but I think for every biomarker, generally speaking, is that that is concentration dependent. So if the biomarker is much higher, the chances to develop AKI are also much higher. So, I think we should look at it that way. And if you do have a patient with a value that is higher, be more aggressive for that patient because the risk to develop AKI is much higher in that patient. So I think that is the main reason for the latest ADQI [Acute Dialysis Quality Initiative] to decide that the biomarkers should have a place in actually assessing the risk to develop AKI.
So, what we had was different staging of AKI based on the creatinine and urine output criteria, but that we now have an additional staging just before that that the biomarkers already increased, but these conventional markers are not. And so we have, like, a subclinical AKI that does predict AKI development. And so if we get used to looking at this, we might be able to prevent AKI in more patients.
Dr. Kane-Gill:
So, Dr. Pickkers, considering this case at hand, and assuming Thomas requires intervention, can you please describe interventional options for this case?
Dr. Pickkers:
Yeah. So I think we should be very clear that we do not have, unfortunately, a specific treatment to prevent or to treat AKI. And I think the reason for that is actually a catch-22 because using creatinine, we are always too late, or in many cases at least, because it’s such a late marker. And now that we have biomarkers, we might actually be able to find new treatments in these patients if we use these biomarkers. So there’s no specific treatment, but that doesn’t mean that we cannot do anything, and as was done in the study of Dr. Zarbock, he showed that if you follow KDIGO guidelines very strictly, you are able to prevent AKI.
Dr. Kane-Gill:
That’s very useful, thank you. Dr. Zarbock, what are your thoughts on your approach to therapy and likely prognosis for Thomas?
Dr. Zarbock:
As Professor Pickkers already said, unfortunately, we don’t have a specific therapy available at the moment. Therefore, we can only apply supportive measures as early as possible. And with the biomarkers, we can detect an increased risk without a damage or even functional decline.
Dr. Kane-Gill:
Okay, thank you. So for those of you just tuning in, you’re listening to CME on ReachMD. I’m Dr. Sandra Kane-Gill, and here with me today are Dr. Alexander Zarbock and Dr. Peter Pickkers. We’re just about to dive into our second case in our discussion on cases in acute kidney injury, applications for clinical practice.
Dr. Pickkers, our second case starts with you. Emma is a 65-year-old female who weighs 297 pounds, which is 135 kilos. Her past medical history includes hypertension, and she runs about 155/100. She has obstructive sleep apnea, obesity with a BMI of 42. She has no history of hospital admissions except for a scapula fracture in 2017. In the last 24 hours, she has experienced acute onset shortness of breath with rapid deterioration. Emma was admitted to a regional hospital with no evidence of kidney injury prior to her transfer to the ICU for the management of severe acute respiratory distress syndrome, or ARDS. SARS-CoV-2, also known as COVID-19, was suspected and later confirmed.
Dr. Pickkers, can you comment on the incidence of AKI in patients infected with SARS-CoV-2?
Dr. Pickkers:
Yes, thank you. There’s a huge variability in the reporting of the incidence, and it’s ranging from, like, 20% to 90%. And I think it’s safe to say, especially in patients that are admitted to the ICU, that it’s at least 50% of the patients that also have or develop AKI in these patients.
Dr. Kane-Gill:
Dr. Zarbock, can you share your thoughts on this topic?
Dr. Zarbock:
Yeah. So, the pathophysiology of COVID-19-associated AKI is very complex and affects different pathways. During COVID-19 infection, different proinflammatory mediators are released that can subsequently bind to the receptors on tubal epithelial cells and it use a tubular dysfunction. Another mechanism that is proposed is a direct infection of tubal epithelial cells and put aside with viral particles. And furthermore, endothelial cell dysfunction represents a key risk factor for COVID-19-associated coagulopathy. So the pathophysiology is really complex, and we don’t understand it yet very well. AKI affects nearly half of all patients hospitalized with COVID-19, as Professor Pickkers already said, and the majority of these admitted to the intensive care unit. So 20% of critically ill patients with COVID-19 we see for renal replacement therapy, and survivors of COVID-19-associated AKI often have incomplete recovery of kidney function at hospital discharge. And this is, of course, a huge problem and also a huge burden for the healthcare system.
Dr. Kane-Gill:
Okay. So both of you have raised some interesting points about AKI in patients with COVID-19. And in general, despite this additional risk in patients with COVID-19, it sounds like we should stay with what we know until we know more by applying standard strategies for risk and stage-based prevention and management of AKI?
Dr. Pickkers:
Yeah, it’s – maybe what I can add to what Alexander was saying that, indeed, it’s partly the virus itself causing the infection in the kidney, as some studies, but not all, show that there was some, indeed, viral RNA in tissue in the kidney. But it’s also the local inflammation that is induced by that, and so maybe now patients are treated during the second wave we are seeing now with dexamethasone, for example, where before they come to the ICU. So, it’s also possible that we will see lower or different incidences of AKI now if we are modulating this immune response. And finally we are also chasing our anticoagulation strategy because we know now that there’s a very high risk of thrombosis and pulmonary embolism in these patients. And this may also be related to microvascular thrombosis in the kidney and also part of the AKI that we see.
And the last thing, I think in my practice, what I also do different now is that in the beginning we were really afraid to give fluids to these patients because they had the pulmonary problem and pulmonary edema as their main problem when they were admitted, and so we were reluctant to give additional fluids. We know now that we can safely do that, and so I think many patients, and some of them also have gastrointestinal complaints following their infection, they are dehydrated when they come in, and maybe we should be not too restrictive in their resuscitation at the beginning that we were in the beginning, during the first wave. So optimal hemodynamics is also very important part in preventing AKI.
Dr. Kane-Gill:
Great. Well, this has certainly been a fascinating conversation, but before we wrap up, Dr. Zarbock and Dr. Pickkers, can you each share one take-home message with our audience?
Dr. Zarbock:
So, maybe I’ll start first. So, my final take-home message is that we need these new biomarkers to identify patients at high risk for AKI. And in these patients, we should implement supportive measures to prevent the development of acute kidney injury. And this is true for COVID-19 patient as well as surgical patients.
Dr. Pickkers:
So my main key takeaways would be for the general population or the post-surgery population, that we can indeed use secondary prevention measures and that they are helpful, especially in the subgroup of patients with increased risk. And this subgroup we can identify using biomarkers. And second, for the COVID-19 patients, I think there are several things that we should consider. We are actually treating their immune system at this moment with dexamethasone. This might affect the development of AKI. We are actually working with their anticoagulation differently, and this might also be of relevance. And their resuscitation is different than we did in the beginning. So, I think that the incidence of developing AKI might be different in the second wave of this group of patients.
Dr. Kane-Gill:
Very good. And I also think of things from a drug perspective, and when we’re trying to prevent drug-associated acute kidney injury, we’re trying to think for prevention strategies as well. If you look at a patient who’s high risk, we know they are high risk. How do we better manage those drugs to prevent drug-associated acute kidney injury? So that’s just another thought to think of for use of these biomarkers.
Unfortunately, that’s all the time we have today, so I want to thank our audience for listening and thank Dr. Peter Pickkers and Dr. Alexander Zarbock for joining me and for sharing your very valuable insights. It’s a great pleasure speaking with both of you today. Thank you.
Dr. Zarbock:
Thank you very much.
Dr. Pickkers:
Thank you.
Dr. Zarbock:
Bye.
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You have been listening to CME on ReachMD. This activity is provided by Prova Education and is supported by an independent educational grant from bioMérieux.
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