Thank you everyone, thank Cristina for the nice introduction. So I'm going to try to talk about the role of the nephrologist in this very complex situation. As Michael mentioned, it's a very common problem in the ICU and really requires a close, very close communication between the nephrologist and intensivist. So I don't have any disclosures. The learning objectives, I'm going to try to talk a little bit about the AKI and the effects on the system in general, how the nephrologist help with hypoxemia, how the nephrologist may help with the management of acidosis, and when to consider renal replacement therapy as a strategy for management of these patients. So I mentioned this to Tango, there is a very complicated interaction between the lungs and the kidneys. So on the first side, you can see all the mechanical ventilation, ARDS complications that make the kidney to fail. So there is changes on the gas, there is changes in the vascular compliance, the increase of the intraveolar pressure, all of that really creates hypoperfusion to the kidneys, develop activation of the renin-angiotensin system, and at the end develop kidney failure. And also ARDS per se, inflammation, as we know now, AKI more than a single issue, it's really a multisystemic process that very often is caused by inflammation, often in different organs, particularly in the lungs and ARDS. Now what happened on the other side, when you have somebody with kidney failure, obviously all of these mechanisms also affect the lung. So the most common ones is volume overload, the second would be the acid bay disorders, the uremic accumulation in blood can cause endothelial dysfunction and increase of the pulmonary pressure in the lungs. All of these create a circle between damage of the lungs, damage of the kidney, and it's sometimes very difficult to get out of this. Now there is no talk about AKI without the definition of safe AKI. So how you evaluate the risk, there are multiple tools, I think the best use now is the biomarkers. So patients, when you consider to have a very high risk of development AKI, these biomarkers are now available, and this is something that you need to start thinking down the road, like when to apply, when to use it, and use it in the right setting, because it might help you to make some changes on the management, or at least create some sort of awareness that this patient may develop AKI, and as we know, patients when develop AKI, the prognosis and the management in general becomes more difficult. This is the KDOH staging, very important to keep an eye on the urinary output, so as we know they go from 1 to 2 to 3, and this criteria was developed more than 10 years ago, really evaluate the rise of the creatinine, but important to keep an eye on the urinary output. There is a new proposal for staging, this is probably going to come in the next few years, where on top of the rising of the creatinine, they now add the biomarker of damage criteria, so basically the TMP2 times the IGFB7 as a marker of kidney damage, probably going to come in the next few years. So now, what is the risk of complications in there? When somebody develops AKI, depending on the staging, the complications are mortality, and also the loss of kidney function might be prolonged, up to 90 plus days. So you can see here, patients who develop AKI stage 1, they have worse prognosis, but they tend to recover urinary function if they get out of the AKI phase faster. Contrary, patients with stage 3, they tend to develop kidney failure that lasts longer, and they tend to develop chronic kidney disease after the initial event. So what the intensives can do, so this is an area where we are trying to revolutionize the management of the ICU, and also the regular floor. So once you have a patient who is at the risk of AKI, or has any of the positive markers, then you start thinking, right, discontinue nephrotoxic agents, make sure the status of the volume is appropriate, the patients have good perfusion pressures, hemodynamic monitoring, and then start avoiding all the nephrotoxins, make the pharmacist make sure you are adjusting the medications, all of those things. Now what happens when somebody develops AKI? Every organ suffers, we talk about the lungs, but the liver, the bowel also suffers, there is a lot of translocation of bacteria and endotoxins that come from the metabolism of the bacteria in the bowels that can cause systemic effects. As Michael mentioned, there is a lot of issues in the heart, including apoptosis, those patients develop low cardiac output, they have a very high risk of arrhythmias. Volume overload is a real problem. As we know, patients in the ICU who require antibiotics, sedation, particularly the patients who are on mechanical ventilation, we don't do anything about fluid balance, every day they accumulate between two or three liters. So you have to be very careful about early use of diuretics, very appropriate management of fluids, give fluids when the patient needs fluids, but don't overload those cases because all of those patients develop systemic effects such as brain edema, myocardial edema, bowel congestion. We know patients with AKI develop higher risk or they are very high risk of developing new infections in the hospital. Now let's move to the hypoxia talk. So 44% of patients with severe ARDS develop AKI. When they develop severe ARDS and AKI, the mortality is as high as 60%. Those patients have a prolonged stay in the hospital and the long-term outcomes are poorer. So in this graph, I try to represent the patients who develop ARDS, patients, the entire cohort, and patients who develop AKI, mortality is much, much higher. The mechanisms for the development of AKI is volume overload, inflammation, uremia. The PEEP, per se, we know can cause AKI in numbers as low as 10 centimeters of water can start causing issues on the perfusion of the kidney because it can cause vascular congestion, right ventricular failure, and start affecting the kidney function. The strategies, as Michael mentioned, obviously make sure the patient is receiving low tidal volume. It was a study very early on the ARDS net. Patients with low tidal volumes tend to have lower cytokine release. And even though it didn't have a lot of change on mortality, we know it reduced the risk to develop AKI. Conservative fluid strategy, there is a clear trend to require less renal replacement therapy. As nephrologists, we always try to find a good dry weight. That's the target for every patient. Not easy to do in the hospitalized patient, but at least having a good fluid balance to understand where the patient came, how much fluid the patient received, and how is the output really guides you somewhat to know exactly where the patient should be. Volume overload, increased mortality, mechanical ventilation, intra-abdominal pressure. These are very important, particularly in some of the patients in the ICU with pancreatitis, burns, or surgery. What is the map for this? It's a moving target. People say 65, 75. At least make sure the patient is not having a continuous episode of hypotension. When to consider renal replacement therapy in hypoxia? It's a collaborative effort. For sure, patients who develop oliguria, and for sure, patients who have volume overload. Once you try diuretics, the patient is not making any urine, the patient is volume overload, it's a clear cut. The patient needs to get some sort of renal replacement therapy for fluid removal. I believe those patients have possibly the best benefit when you start CRT early. There is a lot of controversy on this. There are multiple studies who compare early versus late initiation of CRT or hemodialysis with no difference in mortality. But obviously, those studies, what they do is they pocket all the patients who are in the ICU, but not particularly the patients on ARDS or patients with severe hypoxia. But I believe there is a role for early initiation of CRT. Remember, this is how the regular hemodialysis system works. This is the CRT circuit. Important to understand, patients on hemodialysis, they require much higher flow from blood. That's the reason why it's poorly tolerated, and also the amount of fluid that you try to target per hour is a much higher volume. That's why it's also poorly tolerated, compared to the CRT circuit when you have a much lower venous flow and a more gentle ultrafiltration. This eventually help you to target the patient hour by hour and see how much fluid you can take, how aggressive you can be with ultrafiltration, and even make adjustments to the CRT prescription. To look now, CRT is not free of issues. One of the most common complications is severe hypophosphatemia. CRT tends to remove phosphorus quite aggressively, and hypophosphatemia is associated with muscle failure. We need phosphate to create ATP. So it's one of the reasons why patients stay on the mechanical ventilator for a long period of time. This is one thing to watch. Anticoagulation sometimes is important. The ADQI guidelines recommend the use of anticoagulation to prevent circuit failure. Every time the circuit fails, it creates a lot of issues. One is the blood loss, and the second problem is the constant interruption of the CRT that makes the patient not receive an adequate replacement therapy over a 24 period of time. And when you use C-Trait, which is a different way to use anticoagulation, and there are two different ways to do it, heparin or C-Trait. C-Trait can create metabolic alkalosis, that's something to watch for, and also can cause hypocalcemia. That's the mechanism how the C-Trait circuit works. Now in terms of acidosis and AKI, it's both a cause and consequence. Mike talked about this quite for a good period of time, but just remember the CO2 plays a key role in the development of acidosis, because both can be metabolized to bicarbonate, or can be excreted by the lungs and relieve the acidosis when the respiratory failure is the etiology. There are many other anions and cations that contribute to this, phosphorus, proteins, calcium, chloride, and lactate. So what is acceptable? I believe some degree of acidosis with mild hypercarbia may have anti-inflammatory benefits and may not be as deleterious as other causes of acidosis. Concerning patients with severe metabolic acidosis or patients with mixed metabolic acidosis and respiratory acidosis have a high mortality. AKI, respiratory failure, and acidosis mortality goes up to 60%, has effects on the cardiovascular systems as Michael mentioned. Now what is the role of bicarbonate? I believe the role of bicarbonate is questionable at the most, at least in situations when you have respiratory and metabolic acidosis. It may have a role in patients with pure metabolic acidosis when the kidney is the original culprit or when you have a net loss of bicarbonate, for example, cases with diarrhea. Otherwise, the role of bicarbonate is pretty questionable. Why? Because increased hypercarbia, increased molarity, increased volume, and this phenomenon of intracellular acidosis with issues on the ionized calcium and arrhythmias and brain dysfunction is a very serious one. So in this study, the study actually compared what is the effect on survival between the different grades of pH after two days of treatment. And what they found is that patients who survive have some degree of normalization of the pH. Patients who do not survive, they tend to have poorer outcomes. They didn't see many changes or many difference on the PCO2. They also saw differences on the bicarbonate and also in the correction of the anion gap. So in general, patients who are acidotic and they get better because we correct the acidosis, they tend to have better outcomes. Now correcting the pH change mortality, we don't know that. But we know that patients who correct acidosis can have better outcomes compared to the ones who do not correct or get worse over time. So when to consider renal replacement therapy in acidosis. So patients with a stage 2 or a stage 3 AKI, severe acidosis, or mixed acidosis, that's an absolute indication for a replacement therapy. The numbers, I would say when you have a pH below 7.2, a mixed status with a bicarbonate less than 18. It's again an area of controversy, but I think those are patients who might benefit from early management with renal replacement therapy. Hemodialysis is probably poorly tolerated. Tends to be poorly tolerated. It's difficult to remove fluid. So CRT is preferred. Management of the respiratory acidosis per the ARDS guidelines. Discussion of ECMO when it is the case. And this is an important discussion with the nephrologist. Different studies, particularly the renal study and the VA NIH study, tried to find what was the best dose of CRT in the ICU patients. In general, the 20 to 25 is appropriate. You can try to increase the rate from 25 to 30 to accommodate CRT downtime issues with filter or the patient has to travel out of the ICU. However, one of the recommendations from ADQI is that the prescription dose should be dynamic and really should be targeted to the patient's needs. Again, this is another study that what they tried to do was to find what is the effect of acidosis over time so patients who correct acidosis have a better prognosis. This is just a graph trying to go over the CRT circuit and how to make a continual reassessment to target the patient needs. So for discussion, ARDS, AKI, and acidosis is particularly deadly. There is a complex long kidney crosstalk. The role of mechanical ventilation is basic for the management of hypercarbia. Fluid balance is very important for the ICU. Don't let the patient to become volume overload. Attempt diuresis early. If the patient fails to diurese, be strongly consider CRT. Bicarbonate is a friend or foe. My talk in general is a foe, particularly when the patient develops hypercarbia. CRT in general is better tolerated, at least, even though we don't have many positive outcomes compared to CRT. And what are the CRT targets? Again, this is a personalized or it should be a more dynamic prescription to just leave the patient on a prescription of 25 as we normally do. We really have to keep an eye on the ultrafiltrations. When the patient is acidotic but still needs more therapy, it would be okay to increase the replacement fluid in those cases. With that, I leave Christine alone. Thank you.

nephrologists

acute kidney injury

intensive care unit

renal replacement therapy

biomarkers