Podcast Synopsis of Updates to the European Renal Best Practice and UK Kidney Association Guidelines for Treatment of An

00:00:00: You are listening to an AIDIS Journal podcast.

00:00:05: Hello, this is Professor Mario Cozzolino from the University of Milano, Reno Division, at Santi Pavecaro Milano, the Department of Wet Science and Metrologists.

00:00:15: Happy to welcome you with this post-caste synopsis of the European Best Practices and UK Indian Association guidelines for the treatment of an immune disease.

00:00:27: Today we have two colleagues from UK, Dr.

00:00:32: Socrates Stonkwas from the Wienerland Trust by the Queen Elizabeth University Hospital in Glasgow, UK and Dr.

00:00:39: Sunil Bandadi from the University Teaching Hospital's National National Service Trust in the

00:00:48: UK.

00:00:49: So

00:00:50: after this introduction, I would like to introduce the discussion of the anemia management in non-dialysis dependent and dialysis dependent secret deep patients and the evolution that we had over the time during the last years.

00:01:09: In fact we know very well how important is the iron supplementation in our patients and how we learn how to use the erythropoiesis stimulating agents in deeps.

00:01:21: But more recently new drugs such as diapoxia in this word factor probably like hydroxylacid inhibitors that we are going to call the FPH.

00:01:32: Drugs came to our attention and we can now use the treatment for our patients with CKD.

00:01:42: So in twenty twenty four, the European best practice board at the ERA European Association published a clinical practice document.

00:01:54: specifically covering the use of the HIF in that patient's vesicle.

00:01:58: Earlier this year, the UK kidney association updated its guidelines for Trillianemia of CKD, including this treatment as a recommended addition to terror.

00:02:11: So today, the purpose of this podcast is to discuss the implication of this publication for clinical practice, understand the role of its in treating anemia of CKD and provide practical recommendations to help clinicians make treatment decisions.

00:02:30: We know very well that the editorial OVA's stimulating agencies are the established standard of care.

00:02:39: And minimal changes have been made to the easer section of the UKK guidelines.

00:02:45: The focus will primarily be only on the newer HIV-HI drug class.

00:02:52: So, just start with the overview of the ESA versus EVE and what I would like to ask as my first question, Dr.

00:03:04: Bandari, is what are EVE and how are they different to the ESAs?

00:03:12: But many thanks Mario.

00:03:14: I think people might be aware that HIST PHIs are a class of orally administered small molecules that really mimic the body's response to epoxy, and that leads to a transient inhibition of HIST-prolylhydroxylase domain enzymes.

00:03:30: This results in the endogenous production of urethrapoietin, as well as actually an improvement in the absorption of intestinal iron.

00:03:40: and it's released from the iron intracellular stores.

00:03:44: Interestingly, this release of urethrapoitin comes from the kidney and the liver.

00:03:51: This is in contrast to the ESAs, which are biological agents that stimulate urethrapoitin by activation of the urethrapoitin receptor.

00:04:03: And remember, this is exogenous apoproduction, so very different in terms of how they work.

00:04:09: And in fact, Hestitiasis are probably more physiological.

00:04:14: Good afternoon from me as well and thanks very much for the introduction, Mario.

00:04:18: So when they were first introduced, Isas transformed treatment of anemia in patients with CKT by raising hemoglobin levels without the need for blood transfusions, which was the case up until that time.

00:04:33: However, there are recognized limitations in the use of Isas.

00:04:37: For example, they They have reduced responsiveness in patients with anemia of chronic kidney disease and underlying chronic inflammation.

00:04:48: They are associated with an increased risk of cardiovascular events and there appears to be a dose dependent effect with higher is a dose is associated with a higher risk of cardiovascular events.

00:05:02: And finally, the have an unfavorable root of administrations, especially for patients who attend the outpatient clinics.

00:05:10: They can only be administered either subcutaneously or intravenously, and this may be a barrier for some of our patients.

00:05:20: I think in addition to what Socrates has mentioned is that there's been a wealth of published data which shows that Pith PHIs have been shown to be non-inferior to Isis with regard to raising and maintaining the target hemalbum levels in both non-dalsus dependent and dalsus dependent, a CKD patient.

00:05:41: And compared to Isos, patients treated with FPHIs have a reduced need for iron supplementation.

00:05:50: And this may be partly related to the fact that they seem to reduce hep-side levels quite a lot more than with Isotherapy.

00:05:58: And this results in a higher level of serum iron.

00:06:02: Now, there have been quite a lot of phase three trials in both dialysis-dependent and non-dialysis-dependent patient population, and they have found comparable rates of adverse events when it comes to looking at all cause mortality and cardiovascular events with HIF-PHIs and esoterapies.

00:06:23: And as the board realises, this data shows that HIF-PHIs are as good as esoterapy in terms of reaching a hemoglobin target and maintaining it and in terms of adverse side effect profile.

00:06:36: Yes, moving a bit further with regards to the major adverse cardiac events with the HAF, P-H and T-SAS, the majority of trials have demonstrated that both in dialysis dependent and on dialysis dependent HAF, P-H-SAS were non-inferior to ASAS.

00:06:56: and this has been demonstrated very nicely in a Cochrane meta-analysis including fifty-one studies of over thirty thousand patients with non-dialysis dependent and dialysis dependent CKD showing little or no difference between HA, FPA, ICE and DISAS with regards to cardiovascular death, non-fatal amine, non-fatal stroke.

00:07:19: I should mention here that there are some pulled analysis from individual trials such as a protective trial of VADADOSTAT in on dialysis EKD patients, which showed a signal of high risk for Maze in the VADADOSTAT group, which however was mostly driven by the higher hemipemoglobin targets in this group.

00:07:44: To follow up with and talk about the risk of cancer, this has also been found to be similar between HAA, PHIs and Isis.

00:07:54: and again a recent large meta-analysis of over twenty five thousand patients confirmed that the cancer is was similar between the two agents.

00:08:05: Another interesting point I'd like to mention here is that based on a meta-analysis of eight randomized clinical trials including patients of ISAS versus HAF-PHIs, patients on the HAFs were more likely to withdraw due to adverse events compared to ISAS.

00:08:25: However, and interestingly enough, in the placebo comparator trials, there was a similar incident to adverse events with participants being more likely to withdraw in the placebo arms of the trials.

00:08:36: Thank you both for this analysis.

00:08:38: I think that really we have efficacy and safety data,

00:08:44: so

00:08:44: we should move now to the discussion of the choice of patients.

00:08:50: So, as first slide, it makes or an email of CKD treatment initiation.

00:08:55: So my point now is that now that there is a choice between ISAS and HIV-PH heights, what is the recommended first-line treatment for a patient with anemia of CKD?

00:09:14: Both ERPP and UK Kidney Association guidelines very clearly.

00:09:20: indicate that iron therapy should continue to be the first consideration for patients with anemia of CKD.

00:09:30: And iron deficiency can be classed as either absolute, defined as transferry saturation of less than twenty percent, and ferritin levels either than a hundred in non-dialysis-dependent patients and less than two hundred in dialysis-dependent patients, or functional iron deficiency which is defined as transfer in saturation of less than twenty percent with normal or even elevated ferritin levels.

00:09:58: It is recommended that neither is a nor H-E-E-F-E-H-I.

00:10:02: therapy should be initiated in the presence of absolute or functional iron deficiency until iron deficiency is corrected and anemia persists.

00:10:13: and at that point we should differentiate between functional iron deficiency which can often be addressed with iron supplementation and anemia due to inflammation which is more resistant to iron treatment.

00:10:29: Thanks Socrates.

00:10:30: Just want to add to that for patients who are non-dials dependent or maintained on peritoneal dialysis, the choice between giving air or peritoneal iron really needs to take to account the severity of the iron deficiency.

00:10:44: the potential side effects from oral iron and also potentially intravenous iron.

00:10:48: And very importantly, the available of venous act says because of the prectral root.

00:10:54: And of course, the potential requirements for future circuits, esotherapy and PHI therapy.

00:11:00: And as somebody who's been looking at iron therapy for many years, it's important to recognize we don't really know the best form of iron to give in the non-dialysis and in the non-dialysis patients.

00:11:14: Whereas in dialysis patients in general, it usually is a term we use intravenous iron.

00:11:23: So what I would say based on the UKKA guidelines is in general we say a trial of oral iron remains the first line treatment in non-dialysis-dependent patients while intravenous iron is used for those who are organically reliant or remain with absolute refogs, despite oral iron therapy.

00:11:46: And reassuringly both the European and the UK gardeners advised that the regime of high dose intravenous iron, six hundred milligrams in the first month and then four hundred milligrams every month, used proactively in hemodialysis patients who have a certain is less than seven hundred and the T side of forty percent.

00:12:07: And that is based on, of course, on the large pivotal trial, which I was privileged to be part of, in which we demonstrated there was a fifteen percent reduction in all posh mortality in cardiovascular events using that regime.

00:12:22: Thank you very much for these comments, and we agree that we need to correct item deficiency with either oral irons or PDN, CKD, non-diadysis patients or IV, non-diadysis patients looking of course at the ferritin levels, but after iron deficiency has been corrected.

00:12:46: So what factors should be taken into consideration when choosing between ESAs and HIF, PHIs for treatment of CKD related anemia?

00:12:57: I would like to have your comments on this.

00:13:00: Thank you very much Mario, this is a really important question because we are only in the era that we have an oral incident which is the HFPH inhibitors and we have the traditional issues that are only administered subcutaneously or intravenously.

00:13:16: Both the RPP and UK Kidney Association guidance clearly indicate that treatment choice should be individualized.

00:13:24: and should be based on a number of considerations, including patient preference for oral treatment.

00:13:31: This is something that we very frequently underestimate in clinical practice, and we should keep that in mind.

00:13:37: Another consideration should be dialysis requirements.

00:13:41: Maybe easier for these patients to administer ESAS during their dialysis sessions.

00:13:46: Challenges to administer ESAS especially for frail older patients that cannot self-administer.

00:13:52: And finally, the need for increased iron availability is a hyporesponsiveness or intolerance, which should dictate towards treatment with HAV-III inhibitors.

00:14:05: And the patient comorbidities should also be taken into account.

00:14:10: But we will be working through some of these considerations in more detail and later in the podcast.

00:14:16: Yeah, thank you, Socrates.

00:14:17: I agree with your comments that I would like.

00:14:21: now to third point about what immoblity level and should the treatment be initiated for anemia or CKD.

00:14:36: Thank you Mario.

00:14:38: So based on the UT guidelines we recommend offering ESA treatment for patients with anemia or CKD who are likely to benefit from an improvement in physical function and quality of life.

00:14:50: and of course to avoid blood transfusions which is the last resort to correct anemia.

00:14:55: Although we don't recommend a specific threshold, we do make the comment that the definition of anemia encequidae is a hemoglobin of less than a hundred and ten grams per liter.

00:15:08: In the case of TIFTHIs, our guidelines recommend an itchening treatment after a replacement as we've mentioned previously.

00:15:16: when the hemoglobin is below a hundred and five grams per litre in either non-dialysis-dependent patients or dialysis-dependent patients with symptoms of anemia.

00:15:26: And the reason why we chose that level was because that was the range used in all the clinical trials that were public.

00:15:34: Just to go on further, the initial ESOR-HFPHI dose really is based on multiple factors including the hemoglobin level.

00:15:42: the clinical circumstances and that's really in line with the recommendations.

00:15:47: We've actually made a specific comment that when you start HIF-PHI therapy we recommend that a lower dose should be used in those patients who have been Issa naive compared to those who have previously received Issa therapy because we are concerned about the risk of increasing hemoglobin too quickly in these patients.

00:16:10: That's just a slight word of caution.

00:16:12: when starting these drugs.

00:16:14: Thank you very much.

00:16:15: So as doctor, usually it's easier to decide when you want to start a treatment, but more difficult is to achieve and maintaining the target.

00:16:29: So what are the current recommendations for achieving and maintaining targets immobilized today?

00:16:36: Yeah, so in the non-dialysis CKD patients, the recommended target hemoglobin level with either HAF, PHIs or ASAS is ten to twelve and this had been shown in large landmark nephrology clinical trials and we know that normalizing hemoglobin levels in patients with CKD can be detrimental to cardiovascular outcomes.

00:17:03: I should definitely emphasise here that it is very important to avoid rapid rises in hemoglobin.

00:17:09: For example, a rise of over two grams per deciliter over four weeks, or very high hemoglobin levels of over twelve, and we should stick with a target of ten to twelve in non-dialysis EKD patients.

00:17:25: Just to add to that, in dialysis-dependent CT patients receiving hip PHIs, And the big idols have a similar target of ten to twelve grams per cent.

00:17:36: But in the rest of the world, most recommend a lower target of between ten and eleven grams per cent.

00:17:43: That's really depending on the choice of FKHIs.

00:17:47: Again, it's probably an individualized treatment regime.

00:17:51: You need to decide on depending on the patient in front of you.

00:17:55: Talking about monitoring, there's no real consensus in the community.

00:18:01: some common sense applies as well in the new agents but as a general law based on both the UK Kidney Association and the ERBP guidelines hemoglobin levels should be monitored between every two and four weeks until the hemoglobin target range is achieved and stabilized and then we can move to checking hemoglobin every four weeks thereafter or as clinical indicated.

00:18:30: Again, it is very important to emphasize that as with treatment, the monitoring of each individual patient should be based on his own hemoglobin targets, so it should be individualized.

00:18:47: Okay, but how should the iris status be maintained during these treatments?

00:18:53: That's a really important question, Mario, because As we said at the very start that neither of the drugs, ACEs or FPHIs should be started until the patient is iron replete and it's important to make sure the patient remains iron replete during therapy with using either oral or intravenous iron therapy.

00:19:13: Clearly we may need to look in the future as to what is the definition of iron repletion with FPHIs because of the fact that a sexy absorption and mobilisation of iron.

00:19:24: And that's something for future research to look at.

00:19:28: Yeah,

00:19:29: I agree.

00:19:30: Very good.

00:19:30: So let's just move to specific patient population and treatment consideration.

00:19:39: I would like to start the discussion on the rooftop demonstration.

00:19:44: So what is your point about the circle status?

00:19:50: My patient shows a

00:19:57: Yes, again, a great question, Mario.

00:19:58: Thank you very much for that.

00:20:00: As mentioned before, patient choices are very important.

00:20:04: At the same time, when we see patients in the clinic, they always ask from us to make or to dictate towards their decisions.

00:20:13: According to the ERBP clinical practice document, patients with anemia of CKD or no dialysis dependent

00:20:22: or

00:20:23: are dialyzing via the peritoneal dialysis or are on home hemodialysis treatment, they should be given the option to choose HAFBH inhibitors for treatment of their anemia, if this is more convenient for them and this is to avoid additional injections.

00:20:41: So again, patient preference is very important.

00:20:44: The same is the case for patients who are unable for various reasons to self-administrate or patients who have needle phobia.

00:20:51: And there's quite a big number of patients in the clinic we see with needlephobia.

00:20:56: And in all of these groups of patients, eight PAHI inhibitors should be the preferred choice.

00:21:06: So, and just to add to the comments from some of these, I think the other thing to remember, of course, because the drugs are oral compared to ASAs, which are injections, there's no requirement for refrigeration.

00:21:18: That's something which is becoming of increasing importance in the world.

00:21:22: That might also meet an improvement in convenience for the patient to reduce cold storage requirements in pharmacies and in healthcare facilities and, of course, in the home.

00:21:35: We think about switching patients to oral therapies.

00:21:38: This also potentially reduces the time and resource required by healthcare staff, either in the CKD patients or in the dialysis patients who have to prepare and administer the ECIS injection.

00:21:51: So that's something we need to think about when it comes to the stresses on the health care system and which type limited.

00:22:00: Thank you.

00:22:01: Thank you.

00:22:02: So moving from the root of administration to another point I think that we should discuss about the chronicism.

00:22:08: that Information meaning in our patients is very common.

00:22:12: So Looking at the therapy, how do the therapeutic outcomes compare?

00:22:18: between the EPIHS and ESAs in patients with anemia of CKD and chronic inflammation.

00:22:27: I would like to have your opinion

00:22:28: on that.

00:22:30: Thank you, Mario.

00:22:31: I think this is a really difficult area because we're really learning about this.

00:22:36: We know that patients with chronic inflammation commonly require higher doses of ESA therapy to maintain their hemoglobin targets, and that might lead to more adverse events.

00:22:47: There are various studies, but I'm sure Socrates might comment on the various studies which have looked at this.

00:22:54: I would totally agree with Sunil.

00:22:56: It's a really difficult topic with no definitive answer based on the clinical trial data.

00:23:04: Study of both dialysis-dependent and non-dialysis-dependent patients with elevated CRP have indicated that high doses of HAFPHIs were not required to achieve and maintain hemoglobin targets and this was in contrast to ESAS for which those increases were often required.

00:23:26: However, in all of the published trials, only patients with low-grade inflammation were included based on the CRP levels and patients with chronic autoimmune disease or chronic inflammatory states who are more likely to have persistent inflammation were excluded from the studies.

00:23:46: And as such, clinical judgment is required when determining the best choice of treatment for these patients.

00:23:53: So, I'd like to summarise by saying that although there is signal for an advantage in this stage with HAFBHIs, more data are required, especially in the population of patients with a proper cross inflammation.

00:24:12: Yeah, I agree totally with that.

00:24:15: And that's why in the guidelines both the UK

00:24:39: Thank you very much both for your comments and Well one more aspect is to go for other comorbidities and unfortunately our patients with CKD and they have many of these.

00:24:52: so one point is

00:24:55: it

00:24:56: are either is as of HIF, PHIs recommended for the patients with anemia of CKD and for example a history of cancer.

00:25:08: So that's a difficult question, Marupa, answer.

00:25:12: There was a meta-analysis of face-sme randomized trials which found no significant difference between ACEs and FPHIs in the rate of cancer.

00:25:21: Remember, you're comparing one drug with another.

00:25:24: And of course, in many of these trials, patients with hysteria, as you can see in the five years before enrollment in those trials, didn't actually participate.

00:25:38: And the other problem we have, certainly, is with the data from the HFPHI trial set, the follow-up is too short.

00:25:44: It's only up to about three years.

00:25:46: There is long-term data which will become available to look at the cancer risk.

00:25:51: But, certainly, from the evidence we haven't seen at Cancer Singles for HFPHIs, I'll be interested to hear from Socrates.

00:26:01: Thanks, Sunil.

00:26:02: I would totally agree with you that more data required in this topic.

00:26:07: At the same time, the current data suggests there's no real difference between ISAs and TAFPHIs with regards to oncogenesis and potential for cancer.

00:26:20: And that's why both in the ERBP and the UK guidance, we suggest that caution is recommended when using both agents in patients with a history of cured malignancy or those without cancer for at least five years.

00:26:37: for people with active malignancy or malignancy within the past five years we suggest that both agents should be avoided or used with a thin caution only if absolutely necessary.

00:26:51: but again having said that I would go back to the individual assessment and evaluation of the benefit risk in each patient separately as this may depend on the type of cancer.

00:27:05: Well, the patient comorbidities, severity of anemia and finally expected survival of the patient.

00:27:12: Thank you again.

00:27:13: Just to define a little bit better, another group of patients, we seek these patients with cardiovascular disease, cardiovascular disease or cardiovascular

00:27:23: events.

00:27:24: So what is the recommended treatment for patients with anemia?

00:27:29: We seek it with a history.

00:27:32: of cardiovascular events.

00:27:34: Is there any data on this?

00:27:38: Thanks, Mario.

00:27:39: Yes, there are data on cardiovascular risk in patients and we all know that CKD patients have a higher risk of cardiovascular disease than the general population and this is the more common cause of mortality in our CKD population.

00:27:57: Additionally, an increased incidence of cardiovascular events has been observed with

00:28:02: both

00:28:03: ISAS and HIFPH inhibitor treatment and that may not be related directly to the agents but it has been suggested that can be related to either rapid rises of hemoglobin and that's why I've mentioned before we should be very cautious when we administer these agents or large fluctuations in the hemoglobin level and there is some suggestion that the ISAS itself are associated with higher cardiovascular risk when administered at very high doses.

00:28:35: Evidence also suggests that higher hemoglobin targets are also associated with increased disc of mortality, hypertension and stroke compared to targets of between nine and ten, which is what we're looking to achieve in our patients.

00:28:54: And

00:28:54: that's probably why in terms of the UKK guideline, so it is that we've recommended caution when using ACEs in patients with a history of stroke and caution when using FPHIs in patients with prior cardiovascular disease and also thrombotic events.

00:29:17: I would totally agree, Sunil, and that's why in the Airbnb guideline, we also recommend to avoid HAF-PHIs or use them with extreme caution.

00:29:26: in patients with a cardiovascular or thrombotic event in the previous three months, and used with caution in patients with vascular access and the high risk of thrombotic complications.

00:29:37: We should not forget, though, at that point that untreated anemia can also be associated with increased cardiovascular events, and that should also be taken into account.

00:29:47: Absolutely, sir.

00:29:48: Please answer that.

00:29:49: One thing we'd also remember is that anemia is a strong association for cardiovascular mortality.

00:29:56: all causality and quality of life.

00:29:59: But the other thing that you've mentioned previously just to remind people is that to avoid this rapid rise in hemoglobin because we think that that might be the reason why some of these events occur.

00:30:08: So more than a two gram per deciliter rise were four weeks or very high hemoglobin levels and we put a target over twelve grams per deciliter.

00:30:18: The UK guidelines also suggest that lower dose regime does his PHI treatment should be considered in these patients.

00:30:26: Relevant to that point, we have suggested in the ERBP guideline that in the case of hemoglobin overcorrection, which is not infrequent in clinical practice, we should consider treatment discontinuation for hemoglobin levels of over thirteen grams per decilitres, and those degrees is for hemoglobin levels between twelve and thirteen grams per decilitres.

00:30:49: I think this is also important to keep in mind.

00:30:53: Yes, very important.

00:30:55: Socrates and this is extremely common to have patients with CKD, cardiovascular disorder.

00:31:03: These information are quite important.

00:31:06: I would like to move now in another direction, another group of patients that would follow that are the Kibbit transplant recipients.

00:31:15: So my point is that if you have a patient who was previously on dialysis, receiving it easily or if PH eyes but as recently received the equity trust.

00:31:34: should there anemia treatment be changed?

00:31:37: What is your point about this?

00:31:40: That's a really important group of patients Mario as myself being a transplant physician and because we know that anemia actually is a strong risk factor for both poor outcomes and transplant patients but also an increase in cardiovascular risk.

00:31:55: So we should not forget about correcting the anemia first by of course correcting the iron deficiency.

00:32:00: but for transplant patients the UK guidelines have recommended that we basically follow the same guidelines as a known dialysis patient because really a transplant patient is a CKD patient.

00:32:16: The problem is of course as yet the efficacy and safety of HFPHIs in kidney transplant patients has been poorly investigated.

00:32:25: There really is insufficient information on the potential effects on the immune system and interactions with immunosuppressive drugs.

00:32:32: but there are a few recent case series and independent studies which appear promising showing an increase in hemoglobin and as we mentioned previously better our neutralization in patients with post transplants anemia.

00:32:47: and these drugs are well tolerated with no influence on the the concomitant medications.

00:32:53: so i think it's an area we need to look at more closely but something certainly we shouldn't forget about

00:33:00: the question and this is very important also.

00:33:03: um from your experience on kidney transplant patients.

00:33:09: uh one more point one more group of patients is the hospital inside patients.

00:33:17: So my point is, how should treatment for anemia of CKD be managed if the patient becomes acutely ill or is hospitalized?

00:33:30: Yes, thank you.

00:33:31: Thank you, Mario.

00:33:32: It is a very common question, especially one or patients are admitted other specialties.

00:33:39: In the ERPP document we have made no specific recommendations for hospitalized patients but in the UK Kidney Associated Guidelines the recommendation is that ISA or HAFBI inhibitors therapy should be continued during acute illness, surgery or hospitalization.

00:34:00: They mention also that it should only be stopped if there is a clear contra-education such as thrombosis.

00:34:07: but for the majority of patients they should be continued.

00:34:11: and that makes sense because patients that are admitted in hospital with intercarium tillness they usually tend to have a drop in their hemoglobin during their cutillness.

00:34:20: so it makes sense to continue with these agents otherwise their hemoglobin will drop further.

00:34:26: Exploring a little more the thrombosis complications with HAF-PHI treatment In the clinical trials, there was a signal for higher risk of thrombotic events, mostly arteriovenous access thrombosis, deep vein thrombosis and pulmonary thromboembolism in some of the studies.

00:34:48: There are other studies that have found similar or even fewer episodes of arteriovenous access thrombosis associated with the use of HAF-BI's.

00:34:58: So I think that although We tend to avoid them in patients with high thrombotic risk.

00:35:05: There is still an area that needs more research or more data to come out and clarify what exactly is happening in this patient.

00:35:16: Thank you Socrates.

00:35:17: This is something important because we really have many patients with CKD with such a problem.

00:35:27: So it's time now.

00:35:29: to make the summary of our discussion and we discussed about all the implications of HLOF and PHIS for clinical treatment of an inoxic adipation.

00:35:43: So now we have data in terms of efficacy in hemoglobin correction and maintenance and These drugs are a variable alternative to the Isas for iron replete patients with anemic CKD and may also improve iron utilization and we discuss this in our podcast.

00:36:12: The other point is that the HLF-PHIs may be effective in patients with underlying inflammation.

00:36:22: without the requirements for those.

00:36:24: increase of the further data are needed to confirm this.

00:36:29: We are looking for biomarkers of inflammation.

00:36:32: also, which is the best biomarker?

00:36:35: inflammation of CKD patients, which one should be used in looking at the anemia and then CKD, so future studies are necessary.

00:36:50: Then, caution.

00:36:52: is recommended when prescribe both Isis and HIV-PHIs to patients with the history of cardiovascular events.

00:37:02: So this is extremely important because CKD patients have high risk of cardiovascular disease.

00:37:11: So we have this point of course.

00:37:15: It does not be possible to cover all the treatment consideration up.

00:37:21: of an e-mail security during this postcard.

00:37:25: So this is why we encourage the audience to review the complete data lines for the details for both ERVP and UK data lines.

00:37:39: So with this, I really would like to thank my colleagues, Sonil Socrates, for this Very nice, important discussion.

00:37:52: And so I would like also to ask you to say a few words into our podcast.

00:38:01: Many thanks, Maria.

00:38:02: It's been a fantastic overview and thank you also to you and Socrates.

00:38:07: And hopefully those listening will learn much from this.

00:38:11: And as you said, the guidelines are quite comprehensive and a good read for those who haven't.

00:38:18: I haven't seen them yet.

00:38:21: Thanks very much, Mario, as well.

00:38:24: I also think this was a very nice overview.

00:38:27: I'd like to conclude by saying that, obviously, there are a lot of unanswered questions, but at least we're in a great position.

00:38:36: In our era, having two different agents to treat anemia in our patients with CKT, and that has definitely transformed the management of anemia significantly.

00:38:47: Thank you very much.

00:38:48: Thank you very much both again and bye-bye everybody.

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