 for joining us for another session in our University of the Philippines and the Philippine Health Insurance Corporation's webinar series on stop COVID deaths, clinical management updates on the management of COVID-19 cases and the infection. I'm Dr. Raymond Francis Sarmiento from UP Manila National Institutes of Health National Telehealth Center and joining me and Dr. Susie. Hi, hello everyone. Hi Raymond and welcome everyone to the webinar. I think we lost you for a couple of seconds there, Raymond. But anyway, we'd like to welcome everyone. We hope you're all safe in good health and just like to thank you for joining us today. We have a very important topic. Of course, we all want to learn more about how we can manage patients who have COVID and today we're going to talk about nephrology. So before we go into anything else, I just want to say that this is an initiative of the Philippine Health Insurance Corporation and the University of the Philippines. This partnership is meant to help reach out to all the doctors, nurses, healthcare workers out there who would like to know more about what the Philippines is doing, what is the latest and what's the state of the art in the management of COVID-19. Thank you, Dr. Susie. Traditionally, we would go on to our pre-test poll questions. But before that, I'd like to take this opportunity to thank all the members of the teams who are making this possible, starting with the office of the President of the University of the Philippines, led by Executive Vice President Dr. Teodoro Herbosa, the Office of the Vice President for Public Affairs Dr. Elena Purnia, the TVUP led by Dr. Gigi Alfonso, the University of the Philippines, IPDC, who has been very instrumental in supporting us in the technical aspects and whenever we have technical difficulties, the University of the Philippines, Manila National Institutes of Health and also the Philippine General Hospital and finally the Philippine Health Insurance Corporation. So before we get started with the introduction of our guest speaker for today, who will be talking about a very important topic, let's go to our pre-test poll questions. And those questions, Paul, you could click on the poll section of the Zoom webinar. We have two pre-webinar questions as a tradition and the first one, it reads, the receptor for SARS-CoV-2 in the cell is the option A, A-C-Ace, option 2 is A-1, option C is A-2, and option D is A-3. So please log in your answers and so we could see how many choose which answers and our guest speaker will provide the correct answers towards the end of our webinar. Okay, so far most of our attendees choose option C, A-2, and we will know later if that's the correct answer. So please get into our the poll and answer our question number one. So it looks like we have an extra question for today but that's a happy coincidence point. We're very thankful to our guest speaker for providing that but for question number two, it says, which of the following organs has the highest concentration of SARS-CoV-2 receptor? So most of you answered option A, so option A is lungs, option D is heart, option C is kidneys, and option D is muscle. And then for our third question, which of the following modalities of blood purification can remove cytokines, the options are option A, hemodialysis, option D, hemodial filtration, option C, continuous renal replacement therapy, and option D, hemo perfusion. So there's almost an equal distribution on options A, hemodialysis, option D, hemodial filtration, and option D, hemo perfusion. So please continue on and log in those answers and we will get the chance to receive and hear the correct answers from our guest speaker whom my co-host Dr. Susi Mercado will introduce right now. Okay, well we were supposed to have a short opening remarks from the president of the Filipino Insurance Corporation but we had some technical glitches. I think this is normal in the new normal. He said we'll have to deal with you know technical issues. So we're gonna have the president of field health towards the end just to give a short message but it's my honor to present to you our speaker for today. As you know, COVID-19 in most cases, 80% are mild, but for the 20% who have to be hospitalized. The literature says there's 20 to 30% to have some kind of a renal problem associated with COVID. So we're going to learn a little bit more about that from a very well-known nephrologist. She's a professor at the UP College of Medicine. She's also the vice president of the Philippine Nephrology Society. So my pleasure to welcome Dr. Elizabeth Montemayor. Beth, welcome to this webinar. Thank you for your time here with us today. Yeah, thank you. Thank you very much, Susie. And thank you for inviting me. It is really a great privilege for me to to talk on this very important topic, COVID and the kidneys. And I would like to thank, of course, Phil Health, the UP University of the Philippines, and of course, the National Telehealth, the National Center for Health for Telehealth. And the drive to stop COVID by the Phil Health, stop COVID death. By Phil Health, it's really very important, knowing that there is a high mortality of patients in afflicted with the COVID disease. And the global death rate is about 6 to 7%. But as we talk about the patients with kidney problems, you will realize that this very special group of patients will be very special attention. So I will talk on the COVID-19 and the kidneys and what is the relationship of COVID-19 and the kidneys. And for this lecture, I will talk about the four different kinds of patients that we usually see who have kidney disease. The patients with chronic kidney disease, and most of them will be on ACE inhibitor or angiotensin receptor blockers. The patients on dialysis, the kidney transplant patients, and the patients who are hospitalized and developed a kidney injury. This is data from WHO and it shows here the prevalence of chronic kidney disease in the Western Pacific area. And here you will see that the Philippines has a 9.3 prevalence for the prevalence of chronic kidney disease in the Philippines is 9.31. So if you're talking about the population of more than 200 million people, we are talking really of about 18 million patients having chronic kidney disease. And what is the significance of that? Patients with chronic kidney disease seems to have a high association with severe COVID. So patients with chronic kidney disease will have a three times risk of developing severe COVID-19. And this should be emphasized because patients with chronic kidney disease should be advised to take extra precaution to minimize the risk of exposure to the virus. And the physicians who are engaged in the care of this chronic kidney disease patients should be really monitoring them for the timely detection of disease progression. So most of these patients will be on various medications, but mostly they will be on the drug angiotensin converting receptor blockers or angiotensin angiotensin receptor blockers or angiotensin converting enzymes because this is highly recommended and this is the guide one of the guideline one of the guidelines in the chronic in the clinical practice guidelines. It's highly recommended. So let's look at the role of the reigning angiotensin or the reigning angiotensin. We'll stop at angiotensin and review briefly the pathways. There are actually two pathways. The angiotensin, the ACE angiotensin 2 and 81 or angiotensin 1 receptor and the other pathway which is A2 angiotensin 1,7 to the mass receptors. So we will start with angiotensinogen which is a big molecule and this broken down into a small 10 amino acid molecule by reigning and this substance now is called angiotensin 1. Angiotensin 1 is acted upon by the angiotensin converting enzyme to angiotensin 2 which is an 8 amino acid and angiotensin 2 binds with an 81 receptor and here when it binds to its 81 receptor will cause so many deleterious effect. There's vasoconstriction which causes hypertension, increased fibrosis, increased inflammation, increased thrombosis, increased pulmonary damage which means that there's increase in pulmonary edema and permeability. On the other side here, angiotensin 2 is converted by ACE 2 to angiotensin 1,7 and angiotensin 1,7 binds either to an 8 to 82 receptor or more importantly it binds to the mass receptor and the effect when angiotensin 1,7 binds to the mass receptor is increased vasodilatation, fibrosis, decreased fibrosis, decreased inflammation, decreased thrombosis and decreased pulmonary edema. So in other words, the axis ACE 2, angiotensin 1,7 and mass receptor is counter regulatory to the deleterious effect of 81 receptor. ACE is highly expressed in the different organs and you have ACE in almost organs, central nervous system, upper airway, vasculature, lungs, liver, eyes, heart, kidneys and the gut. The kidneys are affected by, there are ACE receptors in the kidneys and the expression of ACE receptors in the kidneys are higher compared to the lungs. There is 100 times more ACE receptor in the kidneys compared to the lungs. Now unfortunately, ACE is also the receptor for ACE 2 is also the receptor for COVID and you can see here an illustration of ACE 2. It has two domains, one which is transmembrane and almost intracellular and one is extracellular and this extracellular domain, the end terminus, is the site where COVID, the COVID virus can tightly bind to the ACE 2 and when ACE and when this happens the virus binding to the ACE 2 gets internalized and now you have here the virus in the cell and this is where the virus can cause the damage. Now what happens when the virus binds to the ACE 2? It loses its protective effect because it has been utilized by the virus and so the conversion now of angiotensin 2 to angiotensin 1.7 which leads to a state of events which is protective to the body is now in the favor of more angiotensin 2 binding to an 81 receptor and more of the detrimental effects will be seen like fibrosis increase in their reactive oxygen species hypertrophy vasoconstrictive and the gut dysbiosis. There is a small amount of ACE which is circulating of ACE 2 which is circulating and this is caused by the pinching of this ACE from its transmembrane part and so you have here an ACE which is potentially beneficial because it can coat the virus and therefore prevent the virus from interacting with the transmembrane bound ACE and so one one proposed intervention for this and which is being in the which is in the pipeline is the recombinant ACE 2 which can potentially coat the virus and when coated now can no longer bind with the transmembrane bound ACE and will just allowed and this will just allow the body to dispose of this virus. So here is the comparison of the angiotensin level in the healthy and the COVID patients and you can see because of the utilization of ACE 2 by the virus that angiotensin level is higher in the healthy individual compared is higher in the COVID-19 patient compared to the healthy individual. So we see that when the virus loses its combines when the virus combines with ACE 2 it loses the ACE 2 is the function of the the beneficial function of ACE 2 is lost and there again you have a predominance of the effect of angiotensin 2 binding with your angiotensin 1 receptor. Now where is the controversy here? The use of angiotensin enzyme inhibitor and the use of angiotensin receptor blocker appear to increase the expression of ACE 2 receptors and so the beneficial effect will be that there will be because of the increased expression of or the upregulation of the ACE 2 receptors more angiotensin 2 will be degraded and the pathway ACE 2 angiotensin 1-7 and mass receptor pathway will be promoted however the bad effect of this is that there will be more receptors for the SARS-CoV and more virus entering the cell. So what really is the effect of the use of ACE are among the hypertensive COVID-19 patients and here we have this data coming from the Wuhan Wuhan group of one about more than a thousand patients with hypertension 118 of them were on ACE ARB and 900 were on non ACE with a median age of 64 years and what is the mortality rate for for this group? Did ACE ARB affect increased the mortality? No it did not you see the mortality rate for those on ACE ARB was 3.7% while those on non ACE ARB was 9.8% and that is significant and if we look at the Harsards ratio for all cost mortality there is in fact a decrease in the risk of dying when patients are on ACE ARB and for the risk of having of developing septic shock, aards, acute kidney injury or acute heart injury you see no significant difference between those who are on ACE ARB and those who are not on ACE ARB. Okay and here's another study on again on a more than 117 patients 362 of whom were hypertensives 115 on ACE ARB 247 non ACE ARB with a median age of 66 years now the in total in hospitality mortality rate was 11% but for if the patient is hypertensive the mortality rate increases to 21.3 among the ACE ARB users those who will have severe infections and those who do not have severe infections are similar so you have a non significant difference between the development of severe infection and non severe infections among the ACE ARB users and the survivor the difference between the survivors and non survivors are also similar in the ARB in the ACE ARB users. Okay however here is a meta analysis on the studies conducted the outcome here for example test positivity there is no difference significant difference whether you are on ACE ARB the chances of getting the COVID infection is similar however if you're going to see hospital admission this outcome there will be more patients who will be admitted which means that maybe they will have more severe COVID infection when they are on ACE or ARB compared to those who are not on ACE or ARB and the ICU admissions there will be higher rates of ICU admissions among those who are on ACE versus non ACE and among those who were on ACE ARB versus those who are not on ACE ARB however in the use of the ventilator there is no difference between those who would have respiratory failures among between those who are on ACE ARB or not on ACE ARB so knowing this we did a survey the the Philippine Society of Nephrology did a survey among the different training institutions and asked them what is the general approach with regard to renaissance and inhibitor for admitted patients with COVID and 11 of them out of the there were 11 responders so 11 training institutions 91% of them will continue with the use of ACE ARB and only one first one one institution will stop will stop the use of ACE ARB okay however as a precautionary measure we have to balance the potential benefits and harms okay so we balance the potential benefits and harms from continuing ACE inhibitor or angiotensin receptor blocker therapy during an acute infection and this is going to depend on the reason for prescribing many of these patients would take this for long-term benefits like control of hypertension and prevention of deterioration of kidney function however if the blood pressure is well controlled and the and the kidney function is stable we can up to continue using ACE or ARB for standard for those with standard risk of COVID-19 but for those who have high risk of COVID-19 like household contacts or healthcare workers consider stopping now for those who have current benefits like those with severe or uncontrolled severe uncontrolled hypertension or heart failure where the use of ACE ARB is really indicated then continue with the use of ACE ARB even if you're positive or negative for COVID okay then that's just that's a precautionary measure now so to summarize this uh the the chronic kidney disease patients we see that the chronic kidney disease patient is associated chronic kidney disease is associated with higher risk of severe COVID-19 the receptor for SARS-CoV-2 is ACE-2 the ACE-2 receptors reduce the adverse effects of angiotensin 2 not only by degrading angiotensin 2 thereby eliminating or limiting its deleterious potential but also by generating angiotensin 1-7 which exerts numerous solitary and opposed opposite or counter regulatory effects to those of angiotensin 2 through an efficient binding with the receptor mass and the angiotensin type 2 receptors therefore the ACE-2 angiotensin 1-7 mass receptor axis is counter regulatory to ACE angiotensin 2 angiotensin 1 receptor axis the use of ACE ARB up regulates ACE-2 and therefore there will be more receptors for the SARS for the SARS-CoV virus and the use of ACE ARB however the use of ACE ARB is not associated with increased mortality but is associated with more hospitalizations and ICU admissions now let's look at the kidney transplant patients the kidney transplant recipients are really who the immunosuppressed host because all of them have to take multiple immunosuppressants including glucocorticoids, azathioprine, tachyloemus, cyclosporine, mycophenylegmophytil and they have to take these for life to prevent rejection after transplantation and we know that the main role of this immunosuppressants is to suppress the body's immune system significantly reducing their capabilities to prevent infections with the various pathogens so let's look at the kidney transplant patients and this is the experience of the Montefiore Medical Center in New York they had 36 kidney transplant patients with a mean age of 60 years the presentation only 50% of them would present with fever and 22% with diarrhea the mean follow-up is 21 days and in this in this group of patients the main laboratory finding is limpopenia in 79% thrombocytopenia in 68% and they have a low CD3, CD4 and CD8 count implying their very suppressed immune state now what is the outcome of what is the outcome here mortality is very high remember in the general population mortality is only about 6 to 7% but for the transplant patients the mortality is high 28% and two of them came from the recently transplanted patients so eight of these patients this 36 kidney transplant patients eight of them were managed as outpatient and these two who died were among those who manage as outpatient so which means that they initially had very mild presentation but deteriorated rapidly now here's another study and this time from the italian experience they have 20 kidney transplant patients who were admitted for SARS COVID-2 pneumonia and the median follow-up here is only seven days they have been on trans on trans uh they have been transplanted for the average of 13 years and the following were their immunosuppressions when they were admitted the immunosuppression medicines were withdrawn and the medicines the following medicines were given they were placed on methylpedesolone and hydrochloro hydroxychloroquine and the antivirals okay so what happened in terms of course of the disease 87 had worsening x-ray and 80 and 85 percent had escalation of oxygen supplemental therapy and the outcome here you see four of 20 had ICU care six of 20 had acute kidney injury and five out of 20 died so this translates to mortality of 25 percent so the conclusion here is that SARS COVID-2 induced pneumonia is characterized by high risk of progression and significant mortality so remember that the mean follow-up here was only seven days so from admission to death the average is only seven days so what are the characteristics of the transplant patients with COVID-19 they present with diversified clinical symptoms a fever is present in 98 or 90 percent of cases in the general population only about 50 percent of them will prevent with fever they have low levels of cd3 cd4 and cd8 implying their immune suppressed state they have they develop more severe pneumonia they have more rapid clinical deterioration and they have higher and earlier mortality and so the question now is how are you going to manage the COVID-19 patients as an outpatient you can do you can do this as an outpatient but the main thing here is that enhanced protection against the COVID contact with the virus should be emphasized to the transplant patient particularly because of the very very high mortality rate for the diagnostic testing any symptomatic patient with history of exposure to an infected individual should be diagnosed should be should undergo testing if with definitive or presumptive diagnosis of COVID-19 it is appropriate to remain at home if the following criteria are met lack of fever no dyspnea maintaining adequate oral intake and the ability to maintain close communication with their transplant team hospitalization should be considered for patients with any of the following worsening of symptoms auto saturation below 94 significant laboratory abnormalities abnormal chest x-ray radiograph and high sensitivity crp onto executive in consecutive in case and for the treatment strategist we have to watch out for drug interactions for example lopinavir return of year can increase the levels of the crawling moose or cyclosporine and in terms of using the immunosuppressive drugs the cell cycle inhibitors like azetioprine mycophenolate morphotile should be continued calcineurine inhibitors should be reduced and steroid dose should be individualized okay so what is the status now in the COVID era of the solid organ transplantation in the united states they did a survey on the different transplant centers and 88 transplant centers responded most of the transplant centers would suspend their living donor kidney transplant program so 71.8 of the transplant centers have suspended the living donor kidney transplant program and in the Philippines here is the statement of the Philippine Society of Transplant Surgeons we recommend that all living and assist organ transplant surgical procedures will be suspended indefinitely the problems and the challenges in doing kidney transplantation during the COVID time is that are are the following SARS-CoV-2 infection could be missed in both donors and recipients who are asymptomatic owing to the sensitivity issues with the the present gold standard test for the coronavirus so remember that we might have only a 70 sensitivity test for the RT-PCR and we might be missing uh that a symptomatic individual who might be harboring the virus and who are who are about to undergo the kidney transplantation the resources in the present time are scarce because of the focus on the management of the trans the COVID patients there's also this logistical difficulty in ensuring a clean and micro biologically safe pathways within hospitals for transplant patients and there is this increased susceptibility to the SARS-CoV-2 infection in the immediate post-operative period and after hospital discharge owing to the induction therapy and immunosuppressive treatment and emergency surgical procedures like kidney biopsy if there is a allograph rejection or allograph nephrectomy if there's bleeding or there's sepsis from the transplanted kidney or open revascularization procedures may be a bit difficult to perform because of the difficulty in mobilizing the operating room okay now let's go to the hemodialysis patients the hemodialysis patients comprise a distinct population in the COVID-19 outbreak there is a relatively large number of hemodialysis patients we just look at the the data the 2016 data almost 60 000 patients are on dialysis in the united states about 500 000 patients are on hemodialysis and the unique characteristic of this COVID patient is that while the general population has to remain at home to prevent contact with the COVID disease these patients have to come to the dialysis units at least three times a week so they are mobile traveling from home to dialysis facilities and other healthcare settings and they can serve as potential vectors of the infection lengthy treatments and they are in close proximity to other patients in the dialysis staff we allow a six feet distance between these two patients but again that is still close proximity and the hemodialysis patients have impaired immune function and have multiple comorbidities they are hypertensive they have diabetes they have cardiovascular diseases and if you look at the presence of comorbidities the presence of these comorbidities would increase the risk of these patients for severe COVID disease for example hypertension increases the risk by 2.3 2.36 diabetes by two times presence of respiratory problems 2.46 times and for cardiovascular disease the risk of developing severe COVID disease is increased to 3.4 times so having comorbidities will increase the risk of severe COVID disease and these comorbidities are commonly present in the hemodialysis patients what's the clinical presentation of COVID-19 the hemodialysis patients and here's the experience from Wuhan they had 7154 patients on dialysis and 154 of them got COVID were in got infected with the SARS-CoV-2 virus while 77 percent presented with wild or moderate symptoms 30 percent presented with severe or critical symptoms the mean age of this patients is 63 years now look at the presence of comorbidities cardiovascular disease in 68 percent diabetes and 22.9 percent respiratory problems and 3.8 percent and we said that these comorbidities will increase the risk for severe COVID disease the clinical presentation is variable and again you see that they don't really percent symptomatically only 51 percent will have fever 45 percent will have fatigue 37 percent will have cough the most common presentation again is limpopenia and the characteristic chest x chest CT scan finding is the ground glass opacity in spain they have looked into 36 maintenance hemodialysis patients who were COVID-19 positive and the clinical course of these patients they again presented with fever, cough, fatigue but not all of them will only about half of them will be symptomatic the peripheral ground glass opacity is present in 22 in 22 of the 36 patients only and seven will have normal chest CT scan or X-ray now in this particular group of patients the mortality was 30.5 percent so really very high mortality and what are the predictors of mortality longer time of dialysis the longer you are on dialysis the greater is the risk for death or increased LDH level and low lymphocyte count these are markers or purposes again looking at this experience in Spain of the mixed types of end-stage kidney patients 46 patients on dialysis on hemodialysis 46 on hemodialysis 4 percent on pertonial dialysis and 51 kidney transplant patients you again can see that the mean time to diagnosis from onset of symptoms just one day for the dialysis group and three days for the kidney transplant group so the course is quite rapid for them 61 percent would have ground glass opacities and the rest will have a bilateral renal involvement now what is the mortality for this group seven out of 25 in the dialysis group that translates to about 28 percent and six out of 26 in the kidney transplant group died so about 23 percent so you can see really the high mortality of the kidney patients on the dialysis and patients who have transplant again another study in Brescia Italy on 643 patients who developed some of whom developed gov2 infect SARS gov2 infection who are just 37 of them were managed as outpatient 57 were managed as inpatient and of these patients who were managed as outpatient still 8 percent of them died and of those who were managed as inpatient 42 of them died so even if you have a mild presentation where management can be done as an outpatient still there is a high risk of mortality so and this brings us to the point of having this algorithm because patients and maintenance dialysis treatment are primarily a high risk group dialysis facilities dialysis facilities must have in place a method of detecting and screening and managing the dialysis the dialysis patients so in this particular center they use the chest CT scan screening because the results come they get the results much faster than the result of the the throat swab so if the CT scan is normal then they will treat in the routine dialysis they do routine dialysis in the usual hemodialysis in the regular hemodialysis unit if the CT scan shows non-viral pneumonia they can do routine dialysis still but there's an examination of the chest x-ray after 7 to 14 days of treatment and if there's negative or no progression of the CT continue here in the regular hemodialysis unit the problem now comes with those who have a CT scan which shows viral pneumonia if the temperature if the patients wear a febrile they can be dialized in a dialysis in a room dedicated for the COVID patient if the patient is febrile the dialysis is put and hold and they refer the patients to the fever clinic for throat swabbing and if positive they refer the patients to a designated dialysis center so what is the point of emphasis here that the point of emphasis here is that we must have a dedicated COVID this we must have a dedicated COVID positive dialysis center whether in the hospital or in the freestanding unit so for outpatients for patients who can be managed as outpatient they can be dialyzed in the designated centers for COVID positive patients but for the more severe pneumonia they can they have to be admitted and dialyzed in the dedicated areas of the hospital however CT scan is the usual screening test for the patients for the hemodialysis patients but we have to take note that uremic patients will have also findings of ground glass opacities and there's this study before the COVID area on the uremic symptomatic patients and they noted that 45 percent of the CT scan findings will be that of the findings we said we say today as part of the morning of COVID infection so here we might have a patient who presents with a ground glass opacity on CT scan and will be managed as a COVID patient only to find out later that he is not he is COVID negative so in the meantime he has been exposed to the COVID floors and or the hemodialysis his hemodialysis schedule has been deferred while waiting for the hemodial for the for the results of the throat swap so and we must remember that patients with COVID hemodialysis patients with COVID-19 will have different methods of handling their COVID virus among in this 34 patients who had COVID-19 and they did very aggressive COVID testing here repeat swaps every 48 hours they noted that only 20 patients had negative results within 15 days and nine of the patients still were COVID positive after 21 days or until the end of the study so it takes time really for the hemodialysis patients to clear themselves of the of the SARS-CoV-2 virus okay so what is the Philippine situation here a lot of patients in the hemodialysis units get COVID COVID-19 most of them get displaced from his hemodialysis unit because the freestanding units have no capacity to accept the COVID positive patients they cannot shoulder the cost of the PPEs the cost of using single use dialysers and the cost of sanitation procedures there are many and here we have a count of a minimum count of five hemodialysis units who have which have closed because the personnel became infected or because the personnel do not come to work anymore because they don't want to get in contact with COVID-19 patients so this means again that most the dialysis patients from these units become displaced and have to transfer to other hemodialysis units which are full to capacity now for the hospitals which accept COVID patients there's a very slow turn around time for the results of the RTPCR tests and this will and this results through the prolonged hospital stay of the end-stage renal disease patients we know that in the epidemic there is equipment and personnel shortages and therefore national and even worldwide preparedness has to be put in place for this will require a lot of flexible algorithms and coordination and sharing resources and for the hemodialysis patients in the times of the COVID there is really a need for designated COVID dialysis units in the different parts of the country to cater to the needs of this special group of patients some would have resolved some would have some are now reducing the dialysis frequency to two times a week because this means less exposure to potential coronavirus infection for the patients and staff reduction in the dialysis staff work including reduced time for cleaning of the machines between treatments and at the end of the day there's greater spacing of patients because you're dialyzing less patients reduce transportation needs and more importantly the conservation of the very important personal protective equipment but there are disadvantages to the two times a week dialysis even three times a week dialysis is insufficient for the management of hypervolemia and patients are at high risk of cardiovascular events in death during the long interdialytic period transitioning a large population of patients with multiple morbidity to twice weekly dialysis is likely to amplify the risk of cardiovascular events in the longer interdialytic period which in turn will result in undesirable increase in healthcare and personal protective equipment utilization so how do we protect him with dialysis patients and we have this uh uh suggestions from the different societies the center for disease control and prevention the era and foundation societies of nephrology education of patients screening and recognition of symptoms and all the and the use of the PPEs so these are steps in mitigating the spread of COVID in the dialysis unit so in summary the effect of COVID-19 on the hemodialysis patients these patients present with a wide range of symptoms and a significant portion of them being asymptomatic there is prolonged positivity of pharyngeal swabs the maintenance hemodialysis patients are at increased risk of COVID-19 and its complication due to presence of multiple comorbid conditions the logical aspects within the dialysis facility further increase the risk of disease transmission and patients on hemodialysis who develop COVID-19 will have a high mortality 25 to 30 of them will die okay and the last class of patients that we're going to discuss will be the hospitalized patients what is the prevalence of acute kidney injury in hospitalized patients here in this meta analysis of more than 70 000 patients and uh looking at 10 articles the prevalence of acute kidney injury is 0.83 percent let's look at the current situation there here is our census from the philippine general hospital we had 265 cases of may 11 the data was taken may 11 and the patients just referred to the set of the division of the problem we had 50 referrals of confirmed COVID cases so half of them will be the end-stage kidney disease patients on dialysis okay so 24 we had 24 patients on dialysis end-stage kidney we were able to discharge only four patients we had four mortality and that means that we still have 16 patients and what is the reason for this prolonged stay of the patients most of these patients are already stable but number one we still wait for the negative for results of a negative test and i have mentioned earlier that many patients cannot clear the virus fast there is a prolonged stay of the virus and therefore a lot of these patients still remain COVID positive for those who are COVID negative the freestanding hemodialysis unit are really hesitant to accept these patients and that's the reason why we were able to accept only uh to discharge only four of these patients now for those patients who did not have any kidney problems initially but developed a kidney injury we had 18 of those patients we're not able to discharge any of one any one of them yet our mortality is very high 50 percent we still have about 50 at mitten so you see here the high mortality of patients with acute kidney injury and so let's look at this study by Chang in Wuhan in Wuhan of 701 patients who are diagnosed with COVID-19 the median age is 63 years on admission they already have evidences of kidney problems 41 percent with half of them would have proteinuria one fourth of them would have hematuria and some a certain percentage having an elevated creatinine and bun the e gf are less than 60 is pressed present in 13 percent of this case of these patients and five percent of these patients with COVID develop acute kidney injury the in-house hospital the in-hospital deaths in this particular hospital is 16 percent so here you can see the risk for death if you have kidney disease if you have proteinuria high proteinuria the hazards for death the risk for death is 6.5 times 6.8 times the risk for the risk for death if you patient presents with hematuria is 8 is 8.7 is 8.9 times but if you're going to look at acute kidney injury if the patient is on stage two acute kidney injury there is a 3.5 risk of dying and if the patient has stage three acute kidney injury there is a 4.7 times this risk of dying okay so here's another study on acute kidney injury in patients who are hospitalized with COVID-19 this is a retrospective cohort from 13 hospitals in New York who are SARS positive and here they noted that 37 percent of these patients developed acute kidney injury and the development of acute kidney injury actually coincided with the time that these patients were mechanically ventilated so these are the sicker patients those who would need mechanical ventilation would develop acute kidney injury and how did this patient what is the course of this patient this particular patients would develop acute kidney injury the mortality is 35 percent so patients with COVID would develop acute kidney injury one out of three of them would die so in conclusion acute kidney injury occurs frequently among patients with COVID-19 it occurs early and in temporal association with respiratory failure and is associated with a very poor prognosis the COVID the SARS coronavirus really affect the kidneys and here is a study on 26 autopsies of patients who died of COVID-19 patients who died because of respiratory failure the average age was 69 years here they see evidence as they see here RBC aggregates the peritibular capillaries which means that the blood flow to the peritibular capillary was very small was very slow and there are really evidences of acute tribular necrosis and they saw the presence of the virus in the tubules and the podocytes and this is easily seen here in this immunofluorescence studies of antibody staining the virus are seen in the tubules of the kidneys so direct wearing chemo infection of tubular epithelial cells and podocytes are seen in patients with COVID-19 and here's the study showing that the kidneys really have a lot of receptors for ACE a lot of receptors for the SARS COVID-2 and these are concentrated in the proximal tubule okay so here's the concentration of ACE-2 in the proximal tubule and it is not really surprising that these patients will develop acute tubular injury because of infiltration of the virus in the tubules okay again here is the comparison between the staining for the ACE-2 antibody here is the COVID here is the the non-COVID patient and here is the COVID patient and you can see the intense staining so the up regulation of the ACE-2 receptors in the tubular cells of the kidneys okay so what is the basic pathophysiologic mechanism of acute kidney injury in the patient it can be from the activation of angiotensin-2 we said that because of the utilization of the virus because the virus utilize ACE-2 then angiotensin-2 is not is not degraded and now it is fully activated to under and was and is now allowed to do its very deleterious effect okay there is also the problem of the cytokine storm when there is myeloid cell activation and the release of the cytokines and there is a direct cell direct viral invasion of the cells there we we have demonstrated that the virus can be seen in the tubular epithelial cells and the podocyte damage but the virus can also invade the muscles and cause damage to the injury to the muscles producing rhabdomyolysis and rhabdomyolysis is one of the causes of acute kidney injury however the other very important thing is that there are crosstalks between the organs and the kidney the heart and the kidney that's why you have cargerinal syndrome the lungs and the kidney also talk to each other so if any of these organs fail because of the sepsis because of the acute carjuck and lung injury the kidneys will also develop a kidney injury and we have several procedures to do for the patients with COVID who would require blood purification or cleaning of the blood first is to look at the indications contraindications I will go to the other slide to focus all this so look at indications contraindications then start prescribe the blood purification treatment so choose the treatment if the problem of the patient is just fluid overload then we can just go on with the slow continuous ultra filtration if the patient has acute kidney injury then we can do continuous veno veno hemodialysis or continuous veno veno hemodia filtration if the problem is the cytokine storm then we need to remove the inflammatory meditators and this we do hemo perfusion if the problem is ARDS we need support using ECMO a dish with CRRT and if the patient develop a kit liver and kidney injury then that is a very impossible situation okay so what is hemo perfusion hemo perfusion is a very simple process all you need is a vascular access and a blood pump to push the blood to the cartridge and this is the cartridge which contains resin which will absorb the cytokines okay so as blood flows down here cytokines are absorbed and blood is returned back to the patient fluids and electrolytes will not be altered with the hemo perfusion there is no fluid or electrolyte losses here now if the patient needs additional blood purification then the cartridge can be connected to or can be placed in series with the usual hemodialysis that with the usual hemodialysis dialycer so here is a patient who is undergoing hemo perfusion because of the cytokine storm from sepsis and also undergoing hemodialysis because of a kidney injury so what is the role now of hemo perfusion if you're going to look at the invasion of the coronavirus to the organs particularly the lungs the lungs will then need support and it can be done through the mechanical ventilator or through the exocorporeal membrane oxygenation but all of these things will trigger a cytokine release and so for the cytokine release we can opt to do hemo perfusion to remove these medjators which are mostly inflammatory okay here these are examples of the cytokines there cytokines are very complex because they have very very varied actions you have the interferons they are regulators of innate immunity they're the interleukins which have growth and different which are mainly pro-inflammatory the chemokines which are again low in pro-inflammatory and then tumor necrosis factor which are pro-inflammatory and how would the hemo perfusion handle this let's look at this study using a certain um cartridge with which absorb the cytokines and here you can see that interleukin-6 which is a very important pro-inflammatory cytokine is removed by this particular sorbent interleukin-6 interleukin-10 and tumor necrosis factor are removed significantly by by hemo perfusion procedure again in another study we see here the decrease in the various uh in the levels of the various inflammatory mediators this is day one day two day three of the group who were placed on him on hemo perfusion compared to the group who were just placed on standard standard care alone so for interleukin-8 you can see the decrease in uh in the levels of the inflammatory mediators compared to those who are not placed on hemo perfusion and here you see this decrease in the levels decrease in the levels of interleukin-6 now in this particular study it is noted that better clinical outcome is seen if hemo perfusion is started earlier so in this particular study more survivors were seen if hemo perfusion was done less than 48 hours before after admission to the intensive care unit compared to when the hemo perfusion was done more than 48 hours after ICU admission and the length of hospital stay for those who were placed on earlier earlier hemo perfusion the length of hospital stay was shorter if the hemo perfusion was done earlier again uh this is the effect of hemo perfusion and extra pulmonary sepsis induced lung injury again here the patients were randomized to the hemo absorb absorption or hemo perfusion group and the control group and you can see that the duration of mechanical ventilation is shortened mechanical ventilation free days uh do you have um more you have now a longer mechanical ventilation free days you have uh shorter crrt hours which means that the patient recovered from the kidney failure there is shorter duration of stay the icu the icu mortality is much much lower the 28 day mortality is also much much lower and improvement in functional capacity is better okay so here's my last slides and i'd just like to summarize the key points of a kid kidney injury in the SARS-CoV-2 infected patients a kid kidney injury is frequently observed in ARDS patients affected by different comorbidities and the similar findings were observed in the Wuhan COVID-19 infected patients ours associated a kid kidney injury may be ascribed to several causes including an inflammatory immune reaction characterized by an enhanced release of circulating mediators able to interact and damage kidney resident cells the kidney epithelial cell viral infection may worsen the local inflammatory response and consequently the incidence and duration of acute kidney injury comorbidities may be associated with a pre-existing chronic decline of kidney function in a tendency to develop acute kidney episodes identification therefore patients with AKI may lead to better allocation of hospital resources the use of extracorporeal blood purification techniques and antiviral therapies may theoretically limit the systemic and local inflammatory response at least in part responsible for multiple organ failures including acute kidney injury and the mortality rate of COVID-19 patients who develop a kid kidney injury is very high that's the highest mortality rate in the series presented in the in the study presented earlier the mortality rate here is about 38 percent thank you very much for your kind attention thank you so much for Elizabeth that was an interesting presentation particularly struck me was the mortality rate of those who would require dialysis and those who have been affected by COVID-19 is particularly high for 25 to 30 percent um moving on for uh Dr. Rabeth and Dr. Susie I think uh we would we could be entertaining a few questions uh that will be coming in via the qna a few of those questions poll uh have been have started to trickle in the question that we have right now would be uh first one since we are not able to measure il6 here in the Philippines can we use ferritin c reactive protein uh ldh as a substitute to measure response to hemoporfusion and if yes how soon can we expect a decrease Dr. Rabeth um uh the sort of great marker that we're using for in il i l6 interleukin 6 is crp so but if you do hemoporfusion for example we do measure the inflammatory markers also the ferritin and crp after one the one hemoporfusion procedure we will see already the decrease in the levels of the ferritin and crp and and we do see that among patients uh on uh where hemoporfusion was done now interleukin 6 test is going to be available in pgh uh we are already we are already in the process of or i think it's already in place now in the the examination for interleukin 6 okay thank you bet there's another question here are we considering uh are there any proposed alternative therapies for uh chronic kidney disease patients under ACE ARBS infected with COVID-19 well during this time of pandemic uh maybe they can be shifted if they are but of course they are all high-risk no if they're stable and they don't they really isolate themselves they don't they are low-risk patients in the sense that uh they have very minimal contact with the outside world then they can continue with the ACE ARB but if they are high-risk patients they can be shifted temporarily to another anti-hypertensive medicine so we can shift them to calcium channel blockers okay um Immanuel also has another question he asked the first question are we considering for chronic renal disease patients or kidney transplant patients are they considered potential candidates for convalescent plasma therapy well actually it's not contraindicated uh convalescent plus plasma therapy i don't think it's contraindicated for kidney transplant patients okay okay um dr abet there's another question on the q and a what is the average duration of a hemoporfusion treatment usually the the manufacturer will say that we can use only the cartridge for two hours because uh the the resin becomes saturated already with uh with the cytokines it depends it really depends on the type of cartridge that you use in the study by professor ronko he's the cartridge that he used can last for 12 hours so it is a 12 hour procedure but some of the cartridges can only have by manufacturers uh standard they're they're recommended uh two hours although we sometimes extend to three hours or four hours the wuhan group would extend using the same dialyzer uh the same cartridge recommending two hours they would extend it to about four to six hours okay uh next question is uh related to survival rate so survival rate of uh covid patients who underwent hemoporfusion with or without tosi lisumab we don't have any data yet on that so we don't have any philippine data yet and the philippine society of nephrology is actually in the process of conducting a study to look into that no acute kidney injury use of tosi lisumab we are uh we are currently conducting a study on that so we don't have any uh any data yet on mortality rates for these kinds of patients okay uh thank you dr montemayor uh so for for our attendees we will also be flashing our um post presentation survey it is a a survey poll on uh the presentation that was given by our excellent resource speaker dr elisabeth montemayor so uh and those are being flashed now on the screen uh first question is the the presenter demonstrated the thorough knowledge of the webinar topic it's uh it's obviously sort of a light grid scale the second one is the presenter was well prepared and organized third question the presenter spoke clearly and audibly fourth question the presenter used appropriate language with technical medical jargons adequately explained and the last question the fifth one the presenter used appropriate workshop training webinar techniques so as our attendees are answering this uh post presenter questions maybe we could move on to a different set of questions uh there's another question uh dr montemayor um are we expecting electrolyte imbalances in acute kidney injury associated with COVID-19 since yeah a lot of yes yes yeah because there's acute kidney injury and then of course you can expect hyperkalemia and a lot of electrolyte problems here because of the acute because of the nature of the kidney problem yeah okay very much uh dr beth you know there are lots of very positive comments coming here that it's an amazing presentation i think we're all appreciating uh the time that you put into the presentation itself no okay uh okay so there's a question here no you talked about uh the need for dedicated COVID uh dialysis centers would you like to expound a little bit more on what you meant by that because this now has implications for feeling health and for I guess there are a lot of nephrologists who are watching us right now so what what are your can you expound a little bit on how you imagine the new normal for the practice of nephrology given all of the things that you said about the vulnerability of the kidneys to SARS-CoV-2 so uh would you like to expound on that a little bit yeah because it is very difficult to mix the COVID positive and the COVID negative patients in the hemodialysis unit so uh the patient can easily the non-infected one can easily get infected from these patients so it is best that we have really a dedicated hemodialysis unit where the COVID positive patients can go to for their dialysis and then go back to their to their previous dialysis center when they turn negative i've mentioned that in pgh we are really unable to dial to discharge the patients because of the long because we because we cannot get a negative results so we need two negative results before we can discharge the patients and if this takes time and these are various and some of these are stable patients who are just waiting for their COVID results to turn positive so while they're there we cannot admit the more serious patients remember that pgh is a center is a referral center for the more serious patients so if we cannot discharge patients then we cannot accept new ones because we have saturated already our resources so we need this dedicated center which we can cater and which and to and to which we can refer to our stable COVID positive patients uh so that we can accept new new uh new severe cases um there's some new technology that's come out that i just i was just reading about it last night where uh they're actually doing antibody testing using a veno puncture to ml of to ml of blood um which has very high specificity sensitivity it's called architect i think it's um what if you if we had a better test for antibodies would that help you in moving patients uh moving patients from uh COVID to non-COVID? Yeah we just need a very reliable test to really differentiate the COVID and the non-COVID patients so as as it is now there are a lot of patients COVID patients were asymptomatic and they can really transmit the infection within the unit so a rapid test which is very reliable it's going to be really very helpful to discriminate this uh to yeah to discriminate this uh COVID and the non-COVID patients and so we can easily uh we can be reassured that the the infection is not lingering in the unit right so it's still it still boils down to our ability to diagnose now i think that's where we're yes probably we would like to propose um in fact the philippine society of nephrology would like to propose that all hemodialysis patients undergo diagnostic testing because there are so many of them and now i've asked the different medical directors if they have COVID positive patients in their hemodialysis unit and a lot of them are really saying that yes they have uh COVID positive patients in the unit so the number of COVID positive patients in the hemodialysis units is really increasing and we should really be prepared for a greater number of these patients because we cannot stop them from coming to the hemodialysis unit they have to be there three times a week no they cannot stop their treat the hemodialysis treatment yeah then in in the case of um what that means in terms of cost is that we'll have to have extra PPE yeah that's true for dialysis yeah and that's true and that's why a very dedicated hemodialysis unit for the COVID will really um limit the cost of the PPEs because we just give the PPEs to those who will cater to the COVID positive patients so those in the regular dialysis unit where all which uh which cater to the non-COVID patients will just have the usual protection right uh Raymond over to you okay yes thank you dr Susie um dr Beth um another question would be uh related to the clinical correlation of ionized calcium in a high-risk COVID-19 patient now actually we don't i i don't have any uh no any data on that okay uh thank you ma'am and what about any experiences spot doing continuous venous venous hemophiltration or uh CVV HD with a combination of ECMO yeah yeah it is part of the of the management of the patient if they have uh if they have a kidney injury okay and then further questions from Emmanuel Garcia um are we now considering hematuria and proteinuria as significant indicators of prognosis in the course of COVID-19 patients well based on the on the study that it is a significant predictor of mortality so just have to really look at the the hematuria and the proteinuria in price the presence of an existing kidney disease so it just really all boil boil down to that no the presence of an existing kidney disease or the or or the presence of an ongoing kidney injury so if it is present then it just really sometimes we ignore the presence of hematuria proteinuria in the urine but it can prognosticate our patient okay uh are there any questions on your side dr Susie uh uh no more you know i i thought we would be able to get uh fully health CEO and president uh Ricardo Morales to close the program but unfortunately he's in a meeting with the OFWs so uh we will ask we'll ask him to to join us at another time but i just wanted to ask dr Beth uh i know it seems to me that there are a lot of fellows and residents who are listening because the questions are highly technical so would you have some parting words for them or some advice because um it you know uh what we're enjoying about this webinar is that we're able to do a deep dive go back into basic uh physiology pharmacology and really try to understand why we do things because there's a lot of misinformation out there about what should be done and how do you manage patient patients and so on so when we do this kind of deep dive especially for those who are at the front line i think it's very helpful so uh dr Beth do you have any um any parting words for them or uh advice it should like to give them right now yes um for the patient because the fellows and the residents will be the ones taking care of the of our patients and knowing that kidney patients if they do develop COVID disease will have a high mortality okay the main thing here is prevention so if you have a patient with kidney disease emphasize all the preventive measures they are the group of patients who would require this to uh a more a stricter preventive measures social distancing hand washing use of masks all those things the the message is really going to be very simple prevent help us help us help the patients prevent themselves from getting the coronavirus okay okay so i think that's a wonderful way to end our webinar uh and congratulations dr Beth uh there's i'm getting a lot of text messages saying that they really really learned a lot from your uh really learned a lot from your from your talk and um we want to thank you again for your time we know you're very very busy and we hope in the future when there are new updates we can invite you again to to speak so on behalf of the University of the Philippines and all our partners who made this possible and the Philippine Health Insurance Corporation i'd like to thank you our audience all of you who are on the webinar and those of you are watching the playback we hope this has been useful for you that we can continue to learn to share ideas to understand and to network um using technology that helps us cut through our distance and the barriers of time and space that are now preventing us from interacting more so thank you very much we hope you'll make every friday a habit every friday from 12 to 2 we will have these highly specialized discussions on stop covid deaths clinical management of updates on clinical management of uh covid 19 so thank you so much and um we hope to see you next time next time we're gonna have dr gene solante he is the head of adult infectious disease uh unit of san lazaro hospital he's going to be talking about um covid and other infections so if you recall earlier on uh one of the first deaths was a patient with hiv and then covid and tb and so he's going to talk now about all of these interactions among infections and much uh very similar to what uh dr monty mayor has talked about uh having these other infections also presents very high risk for severe morbidity and and for mortality this you all to see you next week thank you very much everyone thank you dr susie and thank you also to our excellent resource speaker dr elisabeth monty mayor before we formally close our webinar for today i'd just like to acknowledge that we are the presence of our attendees from multiple um cities and areas we have attendees coming from region five in be called from part of state university kama rena sewer uh from region two kagayan valley from apayao kagayan medical center from region 10 in northern mindanao misamis oriental provincial hospital and uti was sized in the out ilo ilo which is from region six western visayas and from region eight in carada region this league district hospital in this league surigao del surdo so that's how um widespread po at the talaga po naabot ang ating minister of mail oman yes yun pa sabi ko palang po that that even uh the presentation of dr monty mayor has got international we have attendees po from saudi arabia and also from oman and also from the united states so thank you for imparting your knowledge dr monty mayor and as always uh marami salamat po and and your presentation was very well received uh we are sharing po the poll results uh for your presentation and uh at least 84 percent of your uh of all of the answers po of all of the attendees said that they strongly agree in terms of the acceptability and well preparedness and organization and your thorough knowledge of the webinar topic marami salamat po dr monty mayor and through our attendees po uh tune in next week for our friday habit uh continue to join us from 12 noon to 2 p.m for this university of philippines and phil help bring us to post webinar questions i don't think oh yes the post webinar questions would you mind answering giving the correct answers for the three questions that you gave po yeah of course the receptor for sars-cove uh two is ace two and uh the organ the tessias concentration i've mentioned that the kidneys have a higher expressions of uh the sars-cove two receptor compared to the lungs and for the process of removing the cytokine uh hemoperfusion will be the procedure of choice the treatment of choice okay thank you dr monty mayor i hope everyone got a hundred percent on the second uh second round of answering really learned a lot salamat again dr beth thank you so much thank you very much thank you very much susie for inviting me thank you very much raymond thank you so much dr monty mayor and thank you dr mercado uh for next week's webinar uh we will as dr susie mercado mentioned we were talking about um infectious from i'll talk from an infectious disease expert from the san lasero hospital talking about the co-infections uh for a patient who has COVID-19 so thank you very much keep safe keep healthy and see you online thank you so much thank you