Prof. Dr. Halimi presents current concepts on pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.
Dr. Halimi is Professor of Nephrology at CHU Tours, France, where he leads the Centre d’Excellence Européen d’Hypertension de Tours.
He is author of many national and international guidelines in the field of hypertension, with a special focus upon patients with chronic kidney disease and transplant recipients.
The interview was recorded on May 26th, 2024. Moderators: Dr. Line Aas Mortensen (Odense, Denmark),
Prof. Dr. Dominique Guerrot (Rouen, France), and Prof. Dr. Gunnar Heine (Frankfurt, Germany).
Articles discussed:
Hypertension in kidney transplantation: a consensus statement of the ‘hypertension and the kidney’ working group of the European Society of Hypertension.
Halimi JM, Ortiz A, Sarafidis PA, Mallamaci F, Wuerzner G, Pisano A, London G, Persu A, Rossignol P, Sautenet B, Ferro C, Boletis J, Kanaan N, Vogt L, Bolignano D, Burnier M, Zoccali C
J Hypertens 2021
doi: 10.1097/HJH.0000000000002879
Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients: A Randomized Placebo-Controlled Clinical Trial.
Mortensen LA, Jespersen B, Helligsoe ASL, Tougaard B, Cibulskyte-Ninkovic D, Egfjord M, Boesby L, Marcussen N, Madsen K, Jensen BL, Petersen I, Bistrup C, Thiesson HC.
Clin J Am Soc Nephrol 2024
doi: 10.2215/CJN.0000000000000439
Thrombotic microangiopathies after kidney transplantation in modern era: nosology based on chronology.
Von Tokarski F, Fillon A, Maisons V, Thoreau B, Bayer G, Gatault P, Longuet H, Sautenet B, Buchler M, Vigneau C, Fakhouri F, Halimi JM.
BMC Nephrol. 2023 Sep 20;24(1):278. doi: 10.1186/s12882-023-03326-8
Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH).
Sarafidis PA, Theodorakopoulou M, Ortiz A, Fernandez-Fernández B, Nistor I, Schmieder R, Arici M, Saratzis A, Van der Niepen P, Halimi JM, Kreutz R, Januszewicz A, Persu A, Cozzolino M.
Nephrol Dial Transplant 2023
doi: 10.1093/ndt/gfad095
dear colleagues in partnership with Marcus at home welcomes Professor je Michelle alimi in tour in order to discuss how to handle hypertension in kidney transplant patients a topic upon which the hypertension and the kidney working group of the European Society of hypertension has published back in 2021 a consensus statement with Dr alimi as leading author so Dear Professor alimi it’s a pleasure to host you in Tour on the banks of the lir few days before the Tour of France will cross the region thanks for being with us so M thanks a lot for being here today joh Melle is a very famous French nephologist he has a specialty in hypertension he has been the president he’s the last president of the Esh working group on hypertension and the kidney he’s been longly involved in the French society for hypertension and has been leading the Nephrology Department in tour and the Esh Excellence Center in tour and for this very interesting talk we’ll be with Lyn mortson who is nephrologist in odens in Denmark and Lynn you have been the the leader of the spiron trial who in which you have tested spirin alaon and kidney transplant reion so it will be very interesting to have your point of view on this domain just after Jean Michelle has presented Jean Michelle sit very good thank you very much uh Dominque uh I will present some some slides regarding what we said uh in the consensus and also the last U thing we we we found regarding uh the outcome of patient of kidney trans recipients uh mainly those with h attention so this is tour with the L River uh I live um around here not in the river but on the side on the right side of the river so where is tour first of all tour is right in the middle of of France in this very nice area when you can find um V uh here and we find a lot of V every other Vine wines too but a lot you can find castles and if you like castles you will like probably French Gardens many of them many castles on also as you name it we have like like 30 castles around around tour um at least one of them I’m not able to go there now because my kids were kicked out uh they were they doing too much noise and the the guy at the entry told us that we have to leave so we did I was really frustrated so decided not to go again in a castle but then if you can you can travel on the L River if you do that you you’ll get to tour this way this is uh uh the L on the sun night and you can then cross the river and walk 100 met to the this very nice uh plus uh plus plus plus very nice place anyway with wine all over the place during the night uh very very nice um but we have to work that’s that I understood right not only wine and and and nice places so what about hypertension in kidney transplant recipients at this time um the first thing is that those people the the Physicians involved in the care of patients with a kidney transplantation their main focus is acute rejection chronic rejection antidonor antibody and DSA bath classification immunosuppressive medication C toxicity Bol talks toolbox excuse me from lupy but hypertension is not the main subject uh for these Physicians and uh this is very unfortunate in 201 17 I published that the number of communication regarding hypertension in the main International meetings so in Europe Brussels zero USA Chicago ATC 3 uh Madrid Ira 7 USA ESN one hypertension meeting in Europe Milano two USA New York us zero so this is the situation in in this field I don’t think this has changed a lot since so but at this time I was very naive I thought that maybe we if can write something this will change obviously it didn’t change anything but we were able to write what we call the consensus document regarding what we should do and what we should know about hypertension in in these patients it was based on three systematic reviews so first of all what are the consequences of hypertension in kidney transplant we know that for a long time um Opel a long time ago already and he he did the same thing a few months ago again with exactly the same data but longer followup but the same virtually same data that hypertension at one year is associated with lower graph survival in renal transplantation and the higher the blood pressure the lower the survival it was through 30 years years ago it was through 10 years ago this is all true now probably uh the second point was the pathophysiology of hypertension in kidney transplantation and the factors affecting blood pressure before transplantation or rated to the procedure or after transplantation so we said before transplantation we know that there is an increased sympathic afferent renal nerve signaling for Native kides okay um maybe it’s important maybe it’s not but we know that exists uh during the procedure or just after we know we can have a fluid overload uh increased body weight uh we have problem with the the the situation of the deceased donor and the vascular aspect of this donor ey donor AG uh the sodium retention doe peroperative hyos steroids and the delayed grat function whether it’s an important issue uh after the first of two weeks uh after transplantation is is not sure and then during the long life of the renal patients kidney transplant recipients we have high sympathic activity we can have acute rejection and then sodium retention we have the medication dni steroids we can have TMA in some patients and we publish a few data about that we can have cni Associated nephrotoxicity renal arist stenosis in in some patients and most of them most of these situation are are not that important but one is important is The Chronic allograph nephropathy so what about the the latest guideline at least in 2021 where the latest guideline regarding the use of ambulatory blood pressure monitoring in this situ in this population almost nothing uh KD go erbp es again you name it no reform targets usually not no use of U systematic use no systematic use of ambulatory blood pressure uh advocated this is very unfortunate why it is unfortunate because we know for long time that when you take the blood pressure of somebody with kidney trans recipient chances are that this person will have um not office blood pressure but ambulatory high blood pressure and this is known for a long time in all in all studies regarding this issue many patients have a high blood pressure um uh when they are not in the hospital the second point is uh regard the the relationship between blood pressure and the also um the outcome first the fact that many patients here 33% are non deepers so we know that it’s associated with um very pejorative outcome a very bad outcome a few of white hyp children most have mask hypertension so we know that so what’s relationship between amid blood pressure and reflected Target and Target organ damage in these patients we had 28 articles 22 uh studies so a few hundreds of of patients in these studies and our conclusion I let’s not say more than that but in our conclusions umary blood pressure monitoring reflected Target noen damage more closely than office blood pressure in this patients this is not a surprise and the altered cion blood blood pressure profile was associated with renal and cardiovascular Target or get damaged so what what are the blood pressure Targets in this population do we have a specific or at least defined Target for blood pressure in these patients so we look at the guidelines and I added on the on the corner uh the the guidelines for the last European cety of hypertension recommendation um we have we don’t have a specific uh first of all mention of the situation of kidly transplant recipients and when we have it it is said that well these are CKD patients so probably we have to treat them as CKD patients regard I mean whatever that means because at this point we don’t know exactly how to handle them the last question we tried to answer was whether s certain uh antihypertensive medication uh should be preferred in these populations and it’s a very old controversy it started in the 2006 uh in the same um review Jason in in 206 there was one paper saying that no improvement was associated with ananin com Inhibitors and or ARB regardless whether the patient are R blockers or not the the outcome was the same and um the very next paper was exactly the opposite so two prospective studies very well done very opposite results so not very uh easy to answer so we did um um a systematic review and a meta analysis of this situation and we tried to answer that three years ago what we found is that for death we cannot we couldn’t find any difference regarding um the the anti hyper medication c channel blockers B Inhibitors ars no difference for death for graph loss it was said I don’t know if this is true but this is what we find this in this uh systematic review that calcium channel blockers Hast Inhibitors um were associated with a better uh graph survival for rejection obviously no difference and cardiovascular events also no rejection and finally what all of them could reduce blood pressure and this is very fortunate because that that’s their job but we couldn’t find any difference according to the class Forin probably a c better but potassium was increased with a Inhibitors okay so at the end we wrote again I don’t know I don’t know if we were right to to write that but we said Okay C channel blockers could be maybe not should be but could be the preferred First Step antihypotensive agents they improve graph function and reduce graph loss we should have add that um this medication are much easier to use in the first week or month after transplantation than the other medications of as arbs or or a Inhibitors so lastly I will try to show you what we found in our um what we call Excellence centers and we’ll see that we’re not that excellent in our Center regarding the outcome of patients with kidney transplant transplantation over a 35 year period so we started Renown transplantation in October 1985 I was not there yet Dominique uh um and we did the study over 35 years to see whether we could add new um new interesting data so we included more than 2,000 patients uh who were um received a kidney transplant from 1985 to 209 88 of them received antiy medication at the 12 month visit so we looked at the the blood pressure at 12 month for for one um reason it is that uh these patients had at least 21 outpatient visits in our center before this visit at one year when we look at everything ACC cancer risk cardiovascular risk uh immune suppression everything so at this at 12 month after 21 visits everything should be okay in these patients because we have plenty of time to take care of them so the followup was more than 26,000 patient years and we looked at the risk of death uh we had the 379 death and ESD we had more than 400 ESD in this population so uh this patient were as follow 55 years age two3 of them were male and the GFR was the mean GFR was 55 and the mean blood pressure was 138 over 78 okay so what let’s see what we have now first of all we noticed that um the guidelines regarding what pressure control um varied During the period from 19 85 to 20 or 19 so we decided to compare the blood pressure control according to how is defined the blood pressure control whether it’s 120 over 80 130 over 80 or 140 over 90 so let’s say we take 140 over 90 so you can see that um um this patient were not very often controlled for this uh use of the threshold 140 over 90 but if you say that this should be at 130 over 80 it’s even worse it’s 18% and it’s it’s 120 over 80 it’s 8% and uh we have we have to remember that most of the patients have mask hypertension not white code hypertension so the situation is probably worse that than that and we are what we call an Excellence Center so very very good so then we said okay what the blood pressure control according to salt intake as we have the 24hour or urine nasis of all these patients not all of them 800 of them we looked at the relationship between sodium intake uh below or above two grams of sodium not sodium chloride sodium so it’s like four grams of sodium chloride um whether the blood pressure control would be different again we cannot see any difference nothing um we looked at the situation what we call Therapeutic inertia meaning that physician see the patient they see the problem they don’t act they don’t do anything so with patient among patient with apparent resistant hypertension regardless of the threshold you use 65% of them do not have three anti-hypertensive medication or more so no wonder why they are not controlled second when you take only the patient with protina 50% don’t have a Ras Blocker in all Congress we spend our time saying that they have to have a Ras blocker they don’t have it and we’re neologist we you know the best and the worst part I think is um we looked at the whether they they had a change in management during U this time from 1985 to 2019 well nothing changed nothing changed probably because most of the physician were the same or most of them I don’t know but the situation is is pretty stable then we looked at the situation of patients with at least three or more anti-hypertensive medications and we separated them according to whether they had what we call Optimal uh treatment there is non-optimal treatment maybe you remember in um uh in in 2018 the guideline was that the optimal treatment when we have three medications would be Ras blockers dtic and calcium channel blockers so I look at the blood pressure control in this situation and again you don’t see anything different this is the same thing so I don’t see why we we spend so much time saying that we have to do that but there is no no no difference then I look at something much more important which is the risk of death all cause death according to the blood pressure at 12 months um according to the different threshold we Define 120 over 80 130 over 80 and 140 over 90 so you have three groups normotensive through normotensive we don’t have any medication and the blood pressure is okay uh control blood pressure and uncontrolled blood pressure despite despite antihypertensive medications and during the 30 year or 35 years followup you see there is a difference uh this the difference is significant in univariate analysis and even U not events not even after multiple adjustments so um blood pressure high blood pressure regarding regardless of of how you define high blood pressure is a significant risk of death uh we did the same thing for sodium intake less than 2 gram versus over two gam no difference for the risk of death uh we looked at um the risk of askd in these patients it’s a there is a difference in univariate analysis not in multivariate analysis and um we look at whether what was a difference according to Patient or graph graphon is graph I’m sorry um for optimal treatment versus nonoptimal treatment for those with at least three anti hypotensive medication no difference so um finally what I can say is high blood pressure is certainly a risk factor for death regardless of the threshold used to define blood pressure control I I can say that um is salt intake reduction associated with blood pressure control askd or death I’m not sure at least I haven’t seen that is one class of anti-hypertensive medication better than another one I’m not sure that maybe you have data regarding spiron or F on or any other one but at this time I’m not really convinced and now it’s probably time first of all to use the guidelines and to to implement them and to prefer preferentially use B blood pressure or ambulatory blood pressure monitoring which we we don’t use enough treat patient with sglt2 Inhibitors I don’t have time to talk about it and maybe glp1 receptor Agonist and this is my final um slide I know we’re going to have the tour to France at the end but we’ll also have a very difficult situation in France now with their very difficult tough choices to make for the for the nation uh we have also very bad thing uh that we have in mind um we will probably ready will ready for the Olympic Games if we have the PO the Olympic Gates but at the end of the day we will have the tour to France we will have the V you’re invited to visit us in tour thank you thank you joh Michelle I don’t know if I am depressed because of this because of the low quality evidence-based medicine in kidney transplantation or if I’m excited because we have so much to do in this field I know we have much to discuss about so we’ll start the discussion with Lina ask Mor thank you very much and thanks for for an excellent talk uh thank you very also for laying out your results from the last 35 years I’m certain that if we did it in our Center it would be very similar very kind of you to to make me feel good again that’s the first step right to admit it and realize why we’re maybe not doing H good enough um so you’re advocating for this home either home measurement or H ambulatory blood pressure measurement H what what’s your recommendation how often would you need to do an ambulatory blood pressure or it a one one off or no I would I would do the same thing for the kidney transpant recipients that as I do for the other patients I take care of meaning that um we take we we use um blood pressure once in a while for patients with hypertension and we use blood pressure must very often um just to be sure that the patients are really um controlled so I would do the same thing with exactly same philosophy um but at least in my Center I was not able to implement it and and then uh what would you do then if you have a patient with a very high home blood pressure measurement but fair fairly low office blood pressure so definition of mass hypertension would you treat the home blood blood pressure or would you be scared to make them too hypotensive in fact when I have this situation with home blood pressure um I I try to have a ambulatory blood pressure monitoring just to be sure that there is not a stress associated with blood pressure measurement in the patient with some patient have really have a stress when they they they do the blood pressure monitoring so with ambulatory blood pressure if we I find the same thing I treat them yes yes yeah I don’t care about the situation in in my uh outpatient setting except in the situation when they have um low blood pressure when they get up aut totic hypotension this is different story yeah so symptomatic yeah yeah even asymptomatic even symptomatic or asymptomatic um hypotension when they get up I think there is something wrong with that it’s associated with cognitive impairment with false and so I’m pretty hesitant do you have a lower limit for how how low you will go ER in the blood pressure 120 for systemic blood pressure yeah yes I consider that it’s it’s already very good and before trying to have a even better or lower blood pressure I would try to improve other cardiovascular factors involved such as smoking LDL and so forth yeah um I was thinking also about the dipping it’s quite significant uh numbers of non dipping in our population have you got any thoughts on how is there any way to improve the dipping uh and has there been any indications that that would improve the the cardiovascular outcomes and well we know that you’re right we know that there is a a strong association with between non diming blood pressure and cardiovascular events and death um but uh I I don’t think we have seen um a trial targeting uh only you know the the high blood pressure during night uh I don’t think we have that but even if we don’t have that attend to try you know low those short-term calcium channel blockers um at you know uh in the evening in this situation with very poor scientific background uh to to support it yeah it’s I guess it gives some value to just be aware of of the the risk as well I suppose yeah yeah I sure of you yeah the regarding the choice of of Agents uh so I heard you’re advocating to use calcium channel blockers at least in the early phases or uh would you differentiate between the proteinuric patients and non genic patients and what what uh drug you use as the First Choice well I I I tried during the last for the last guideline not the last the guideline before in 2018 um to to make them right that protenic patient should have RAs blockers in CKD I did not succeed but in 2023 I think this more clear in the in the European guidelines I hope at least uh so yes we have to use these medications and regarding the classes um I always thought that um mras would have a strong or interest in K transplant recipient not only because um they lower blood pressure not only because we reduce fibrosis in many models but also because they increase the T-Rex and you know when we’re in the business of kidney transplantation uh you like to think that also you you have kind of action in immunology and we know for example the spirol Acton increases T-Rexs in in patients and in animals too first in animals but in patient too so I thought that maybe it would be a good idea we start we tried to do it in in France in our Center but the head of the transplantation unit told us that we were crazy to even to think about it so um it stopped right right away okay I think we’re probably crazy then yes I know I know I know you were right to try yeah yeah at least the the the theoretical there was a many different aspects of how it could be uh beneficial but it’s not always easy to and that’s another thing with these um these hypertension uh issues in in um kidney transplant patients the the evidence from the hypertension trials or um Ras blockers for example in kidney transplant patient is U much uh weaker than the CKD population so it’s it’s a difficult and I I liked your outline of the the the like the very different um H Genesis of hypertension in kidney transplant patients whether that’s part of the explanation it’s not as it’s not as easy to show ER significant results I agree I totally agree if I can go a bit further um what would be your dream RCT to show that one class would be better than another because the outcome is not easy if you’re going to show an outcome on kidney function this this does not work in the in the I mean middle siiz studies in CKD patients so I don’t know if it will work in in kidney transplant recipients apart from the hemodynamic effect which is not something very interesting or will you look on other outcomes I mean of course not just on blood pressure control but if you have to have a composite outcome on cardiovascular events Etc it’s also a big population what what would be your dream RCT imagine the P the French program can give you two million EUR what would you do to show benefits well if they give me2 million EUR I stop Nealy and I go to the club mediterrane for a while but um to be serious I think we should do the same thing that the other did in the non kidne transplantation field meaning that we have to have um 3,000 patients followed up for 3 to four years and then we’ll see and we uh the the the the outcome will be a combination of ESD or change in GFR dimin of GFR at least 50% and and cardiovascular events exactly the same ones but uh I’m not sure I that I will see that first of all because it’s a tremendous number of of patients who have in in in a trial second because um the industrial aspects I mean the financial aspects not only the money you you use for the for the treatment of this patient but also um whether they will be able to have a new um you know a segment of population to treat and to have agreement administra agreement to use this medication and remur reimbursement is a really tough business so so I don’t think it be possible to to have this rcts but this is what I’m dreaming of right now okay so I agree so I think we’re going to stay with quite low quality evidence and just I just want to come back on this coun channel blocker because this is one of the uh the main guidelines that’s going around and uh so Lyn said okay in the first year but I mean Beyond this um this this is really low quality evidence do you agree I mean it is a problem because uh people just remember this this and this guidance and don’t always take into account the fact that that you can have interactions with other treatments depending on the type of coun and Chan blocker you you choose um I’m a bit personal with this recommendation to be you’re right we we wrote that and it was based of the systematic review so it was not only the opinion of the the authors but we found that in the systematic review so we wrote it but even if we wrote that I’m not sure we are right I’m not sure about that I think um my point of view is first of all um lower blood pressure be sure that the blood pressure is really lowered not only in at the outpatient visit but at home and then we can discuss the kind of medication you’re going to use and at this point we don’t have any high quality data to to choose among the different classes of of medication except for those with po or heart diseases that we can say something for the other medications it’s it’s pretty dramatic not only because we don’t have any data but because those implicated with renal transplantation don’t have any um profound knowledge of the pharmacology of the anti-hypertensive medication and cardiovascular drugs for most of them and since the the the training of the the residents and the medical students tend to be excellent of course in France absolutely excellent but still probably do not meet the needs uh I’m not very convinced that um this will change um at least during the 21st century for those who don’t know T um I think there’s a very interesting thing it it is an excellent Center in hypertension and in kidney transplantation to be honest the team is a very high quality team of nephrologists and uh I really enjoy the fact that joh Michelle shows the the difference between what the guidelines say and what the Excellence says and what really happens in practice because I think this is something we always tend to to put down um in the real life we don’t really do what we should do even even if these are Physicians that are high quality Physicians and this is one of the really interesting points and I think um my question there is how could you change things to um to make the Physicians do the uh do the change to to go against therapeutic inertia do you I was thinking about um setting one consult maybe the the 12 month consult where where there is a clear objective to change the uh the blood pressure treatment because when you see the kidney transplant patients every 3 6 12 months or don’t know depending on the on the time of the of the the autograph uh implementation then um this is never the first problem it’s always the end of the consult so it has to be a goal otherwise it really depends on the position I don’t know how how we could change this we we did that and we started that last year in fact so we’re on the same line uh we did that um last year and we started a a dedicated um visit at four month uh not uh focused on the imuno supression or uh the the the GFR or prot or anything but you know the cardiovascular situation of the patient whether they had the home blood pressure results or not whether they had the the right medication whether they had aspirin for them who who should have that or or statins for example so we did that I think that’s an improvement uh for these patients the second thing I have in mind is the fact that physician should not be implicated in blood pressure management um the the worst person to to take care of patients is the physician I think we should have only nurses and technicians or or pharmacist because pharmacists you tell them okay the blood pressure should be lower than 130 un otherwise you have to use this medication at this dose they do it the physician is smarter it thinks is smarter so it’s so smart so that he find so many explanation for the situation he doesn’t like so that at the end of the day nothing changes so we have to stop seeing patients one this is my opinion are they I quite agree with this and well our experience is that having a nurse working on blood pressure control is a very efficient much better much better been having this for two years and it really helps not in kidney transplant patients but in hypertension patients and well we do it now for T monitoring and it works just fine much better than what we do on the daily basis and do you know whether there is um measurements of uh compliance to the treatment in kidney transplant recipients where whether it’s better or worse than in other other patients because this could also be a f I think Michelle berer did it at one point and in not they did it they they did it too so it was a long time ago I don’t remember the results but now in in our Center probably in yours too we measure not press concentration medication concentration I mean and U we realize that the more we add the medication the less they take it uh take them so um we have to see that and to to be very systematic at least in patient with res apparent resistant hypertension in those patient we should have systematic drug dosage assessment okay just have a last more theoretical question and then I leave it over to now um it’s about renal Innovation because uh kidney transplantation is a model of renal Innovation but you still have the native kidneys that are there do you think um it learns something about how blood pressure is controlled or not controlled by the sympathetic system by does it learn something about the fact that the native kidneys still have a major impact or whether blood pressure here is totally overdriven by other mechanisms in which you have of course shown in your slide I’m not I’m not sure about to have the right answer I don’t know what you think guys but um first of all I think there is the nervation at one point but after a few weeks or month or more you have R ination uh of the kidney of The graft so I’m not sure it work it is the right model to uh to assess this um cause of of hypertension I’m not sure about that thank you so my first question would be on your last slide where you indicated we already need to drink so uh two questions maybe on lifestyle we have been rather well strong with our recommendations on salt intake and recommend uh an amount of salt Which is far below average intake at least here in Germany so when I do 24-hour measurements in our patients I see a mean of say 10 or 12 or so grams so salt not sodium but salt uh and we still recommend five or six grams of salt and now we show us that you can not really discern different responses between these people do we really have to stay with a strict recommendations and then at the second time uh you you roached on your slide we all already need to drink so what about alcohol do you have uh well it’s a hard question for French position surely but do you give your your transplant patient a recommendations do do not drink more than say one or two glasses of wine per day or uh how how do you uh recommend them well first of all yeah that’s a very important question um for salt intake I’m Amazed by our ability to promote guidelines and not to uh Implement long-term trials just to be sure that those implementation uh which have a consequence on the lifestyle of patients and the quality of life are not substantiated by results I’m Amazed by that we tell people to change their way of life it’s very difficult to do it’s an effort for them it’s it’s we don’t know whether whether it works or not but we believe that maybe it’s true maybe we are right to say that but for God’s sake let’s let’s demonstrate it and we’re not uh so at least in in our patients in 800 patients with a salt intake not only at 12 month but also at three month and six month the results are the same no relationship with risk of death or cardiovascular events or ESD so I’m not sure we have to continue just to play We Are The Physician we know what to do and you will do what I tell you to do we have to do not to show not the the data for alcohol intake um I I tend to ignore the subject but maybe probably I’m wrong especially in our area and again I guess it really depends also in how far people are willing to well change their lifestyle but fully agree and I see not many people but some people who really follow your advises and when they try to follow your advises our advises on salt intake this is really a dramatic change in the way they eat and there are even some people who have problems then to go to dinner parties or something because they afraid to do some damage to their transplant in this case transplant or even to their native kidneys so I guess it’s really as you said important to not to overemphasize this um a second question then would be you said in the interest of time you did not mention sglt2 Inhibitors but in the interest of my interest I would briefly like to know from you do you give transplant patients regularly sglt2 Inhibitors or are you still waiting for the life cycle trial we we do uh we do and we have over 200 patients not only in our Center but in our um network of centers called Astra uh more than 200 patients with under sglt2 Inhibitors without salt I mean side effects and um so we we we do it right away maybe we are wrong but we do it but you don’t see a prohibitively high increase in urinary tract infections or genital infections so that works fine in these patient we have not seen that in most patient I’ve seen uh quite a few urinary tract infection um nothing bad not very different from what I saw in the trials and what about phaneron so we will have Lina ant in two weeks on her spiron trial but with regard to novel Minal receptor antagonist so again do you use them in diabetic patients who have received a transplant would you rather wait for further data I think fin renon is a a very good drug and I think we should try to to use this medication even in kidney transplant recipients especially because the risk of hypoc calmia is not so high even in those patient with a cni treatment but in France so you know where the so we don’t have finon in France and we’re not ready to have have it for the but for now at least we don’t have it it’s not marketed in France for nobody no we don’t have F in France didn’t know that actually no no so it’s very sad but that’s the way it is okay all right yeah what we got to kelum channel blockers so they are not all equal surely and Dominique already alluded to interactions so if we follow the recommendations or The Meta analysis do you have one calcium channel blocker that you would specifically recommend us not to use or to use or can we just take any uh we we tend to use those with a improved cardivascular um outcome in patient with CKD or hypertensive hypertension I mean outside the field of kidney transplantation so we use basically amlodipin um we try to avoid dilm or vam um and we look at the their interaction with other medications even I’m loing some small interactions but all of them have some kind of interaction with some other medications including cni um but we main at least in in tour and I guess all over all over the world the the most use is probably Amin I guess I don’t know if that’s the case in in your countries yeah definitely so 90% I would say in in Germany I don’t know in Denmark Lena uh yes also ER or at least any version of the dihydro so not the DT version so yeah and then maybe one or two questions on the causes of hypertension so you did much work on TMA and you also wrote some recommendations on renal artery stenosis so in which patients do you screen or do you consider um to patients to have either these are two different uh Fields but TMA and uh how often and how do you check for real artery stenosis oral atosis we tend to check it um very early during the transplantation the first week then the first month at 3 months six month one year with Doppler and then we have we also do it every year uh we have the Doppler of the graph artery of the graph every year and we uh um we we do we do an nure scan in patient with resistant hypertension and any suspicion of rear stenosis so we are very uh where we want to not to to to to lose this this diagnosis and to be sure that the patient are not um are not forgotten for this cause of hypertension um but mainly this is this is not only hypertension the problem with r arter stenosis this is more about the GFR Evolution and the GFR under use of Ras blockers and as you know the r aerosis in in kidney transplant is not about fibrodisplasia or or at aerosis it’s more about the age of the surgeon and um also some kind of immunological other changes but more the age of the experience and of the surgeon so it’s mainly during the first year we when we did the systematic evaluation of renal stenosis in our patients during 10 or 15 years it was like 6% of the patients U not all of them did we decide to um to have anoplasty in some patient we did not do anything we just waited and in some of them it was okay but we I remember we we lost at this one patient The graft of one patient because of rosis um which progress to occlusion but I think it’s it pretty aare um for for this situation for TMA um we found that um it’s a pretty rare situation except during the first month of um of transplantation of renal transplantation uh when it’s not that rare uh especially in patient with teog globulin in those with DSA and um in those with cute rejection and also not rare in patient with failing grafts and in these patients uh when we look closely at the biologic results you can find also um tmas in the other situation I mean not at the beginning of the graphs not in the fing graph at the end on the life of the graph is pretty unusual it was said for a long time that it was due to cni over overexposure to cni but what we found during the last 10 years is the fact that cni alone are very are not very frequently Associated to TMA but the association with mtor Inhibitors and cni yes it’s it’s a problem that’s the first thing the second thing is about CMB infection ctoa virus infection we know that in some of these patient they develop they tend to develop TMA even in the if the the virus is not in the blood for example they have a virus in the in the in the gut uh but not in the blood they can have anyway the TMA and the the treatment is not that easy and I’m not talking about obviously the the recurrence of typical hus that everybody knows um in some acute imoral rejection we also have TMA so we tend to um suspect TMA in patient with failing kidneys with you know accute K injury in these patients um and in those with anemia and tropia and we don’t know exactly why but it’s not the diagnosis not very easy especially because some patient will have renal limited TMA especially associated with DSA so the the if you don’t do the the the biopsy you don’t see it um so it’s a changing field I think in in presently thank you one last question Dominic if I may so I think we all feel a certain degree of disillusionment when seeing that the last two or three decades few things have changed in transplant Mets whereas nephology saw so many changes in the last years so looking to the future is there anything you would s um suspect to change in the well upcoming years so will we see new immunosuppressive medications which cause less hypertension where we see new anti-hypertensive agents I’m quite sure I think nobody of us considers to use uh small interfering rnas in these patients like Zan or something but is there any optimistic outlook for the upcoming Years first of all I think U uh we can control blood pressure uh in most patients even in kidney transplantation if patients are not controlled for most of them um it mean that we don’t try to do it in at least 85 to 90% of them they’re not controlled because we don’t take we don’t take care of them the way we should that’s my main point the second point is that if you have nurses pharmacists tele monitoring I think it will help a lot and for new medications I think we have a new wave now of medication that could prove interesting in kidney transformant recipients anti-in medication backa Spira alct aldosterone sentes inhibitor example Fon I don’t know about that it’s not about so much hypertension but but rather uh the the effect of cardiovascular risk and R risk so we’ll have um many other medication and and Pathways to use and to try in in renounce transation but at the end of the day it’s not so much what kind of medication you use but whether you’re you’re really convinced that this is an important issue joh Michelle thank you very much this Recon syney transplantation hypertension with politics you can do it you can yes you can do it that you are involved thank you very much for this great presentation and discussion to all and see you bye thanks a lot see you byee I [Music]
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Thank you very much!