Slide 1

Ladies and Gentlemen, I thank the organisers for inviting me in to talk about looking at renal artery stenosis in high risk populations and what are the interactions of cardiologists and nephrologists here. I’m a nephrologist but I have a lot of friends that are cardiologists and there are a lot of interactions some are even married to cardiologists and when we look at the populations that we both see the question often arises whether we should or we should not look for renal artery stenosis and how we should treat those patients and that’s what I’m going to talk about.

Slide 2

Now, for working on this talk there are a number of good recommendations and literature, overviews like the K/DOQI guidelines from 2003, then very recent guidelines from the American College of Cardiology and the American Heart Association combined and the American Heart Association Science Advisory committee recently in Circulation. So there is quite some interest in this topic of when we should look for renal artery stenosis.

Slide 3

One could argue well why don’t we look at everybody who has hypertension, for instance, for renal artery stenosis and as already pointed out by Professor Kalra, the prevalence of renal artery stenosis in otherwise healthy people, let’s say below age 50 with mild-to-moderate hypertension is low so below 1%. As I will show with the next slide with such a low prevalence of any disease a test must have 100% sensitivity and specificity to be good enough for screening not to cause excessive cost and we don’t have such a test. Now in people with signs of atherosclerosis which both the cardiologists may see and we may see, the prevalence seems to be higher but very variable prevalences are given in literature as I will show later especially in smokers but often there the renal artery stenosis is not associated with hypertension or renal insufficiency at least not severe cases and therefore, the question arises whether it’s useful or not to look for renal artery stenosis and do something for the renal artery like a PTA which has its adverse effects and some severe adverse effects. Some people die from PTA no doubt about that.

Slide 4

As promised this is the slide showing on the left hand the cost per patient treated on the ordinate related on the abscissa to the prevalence of the disease. So when the prevalence of the disease falls below 10%, cost of screening is on rise excessively, so that for each patient that is found with renal artery stenosis, cost of the treatment exceeds 30,000, 40,000, 50,000 dollars. Now, this is in UK cost and on the right hand side you see in comparison the cost of drug treatment so that’s also not negligible but it’s definitely lower just looking at cost and this does not look at adverse events.

Slide 5

Well, given those incidences of renal artery stenosis, the cost associated with screening and in the background the adverse events of intervention, what do the guidelines say and in whom should we look for renal artery stenosis? Certainly treatment-resistant hypertension, hypertension with unexplained renal insufficiency as outlined in the talk before and I will stress here especially with decreasing GFR,  – reminded me of a paper from the Netherlands in JASN 2001 and there was previous data from the Vanderbilt group showing that people with decreasing GFR and renal artery stenosis benefit from intervention, while those who are stable for a long time, let’s say several months and several years before intervention they do not benefit.

Malignant hypertension, there’s increasing prevalence of renovascular disease in malignant hypertension. New onset or worsening of hypertension at extremes of age. All the above with signs of atherosclerosis and I’m speaking obviously mainly about atherosclerotic renal artery sclerosis. A decrease of GFR with an inhibition of the renin system, unexplained difference in kidney size, smoking most people with renal artery stenosis smoke even those by the way with fibromuscular disease and a history of flash pulmonary oedema and I’ll speak about that with a case later on.

Slide 6

Now, the K/DOQI guidelines say what I’ve just shown on this slide that this is the scenario which should provoke looking for renal artery stenosis. However, there’s no prospective trial, I want to tell you that evaluated outcomes and costs of restricting renal artery stenosis screening to this subset of the people we are seeing and it has not evaluated the side effects of the following interventions. So there is a problem, especially as you know the interventions are clearly not better than medical treatment.

Slide 7

Where are the interactions then between cardiology and nephrology? Well, people with coronary artery disease undergoing coronary angiography so those that are put on the CAT table should the cardiologist when he’s going by the kidney just have a look at it or not? A decrease in GFR with the inhibition of the renin system for treatment of hypertension, a decrease in GFR with inhibition of the renin system for the treatment of heart failure those people are normotensive as a rule but it’s been shown in a number of studies that even with normotension and heart failure the prevalence of renal artery stenosis when the underlying disease of heart failure is ischemic heart failure. You have significant number of people with renal artery stenosis in the range of 5-10 %. Flash pulmonary oedema is also something that both cardiologists and nephrologists are looking at.

Slide 8

Now when you go into the literature and try to get a number out for the prevalence of renal artery stenosis with these conditions, one comes up with about a prevalence of renal artery stenosis of 20% in those with treatment-resistant hypertension, of about 15% in those with hypertension with unexplained renal insufficiency, I underline unexplained especially in those with decreasing GFR and there’s no explanation for it. If there’s a decrease in GFR with an inhibition of the renin system, prevalence is at the most 10%, that’s a range, most people have a high dose of diuretics, or otherwise they are in the low volume state. Coronary disease, wide variations in the different trials but 10% is a good estimate of the different publications and heart failure about 5-10% prevalence of renal artery stenosis with normal blood pressure as I said before.

Slide 9

I will come to the coronary disease in a little bit more detail with this slide. I have listed here just to give you an impression what people found a number of data from various publications. In the first one 1200 consecutive patients undergoing coronary angio, of those 60% had coronary disease and 10% had in addition renal artery stenosis and the severity of coronary disease was correlated with the severity of renal artery stenosis. Another study 300 patients, 12% prevalence of renal artery stenosis, 600: 9%, 500: 18% and the last one 4000 consecutive coronary angios well done study renal artery stenosis in this case only 5%.

Slide 10

So that’s about the range that you can expect. On the other hand if you have somebody with renal artery stenosis and ask the question is there an increased prevalence of coronary disease? Yes there is. But there’s only one small study that I’ve found that is given on this slide 23 patients with renal artery sclerosis where 17 had coronary disease.

Slide 11

Flash pulmonary oedema one should not forget about this disease so although the data that reminds us of this problem are rather old and a landmark study in the Lancet about 20 years ago collected 55 patients with azotemia and renal artery stenosis and showed that a quarter of them had a history of flash pulmonary oedema, so of sudden onset of pulmonary oedema. Another study which asked this question 90 consecutive patients with a PTA of renal artery stenosis elicited the history of the pulmonary oedema in 30% ,so that’s pretty close to the Lancet study especially in those with bilateral renal artery stenosis. There are also intervention studies but only on the level that there’s no more oedema after intervention. Recent data from the New England Journal indicate that the pulmonary oedema’s not necessarily due to systolic dysfunction but rather to diastolic dysfunction so when you do an echocardiography or any other study after treating the patients and only look at systolic function whether there is any evidence for systolic dysfunction, you may not find it. Nevertheless, it’s the diastolic dysfunction which is leading to the problem.

Slide 12

For this disease I would like to show you a case. The case was published in the British Medical Journal about 2 or 3 years ago and I have seen several similar ones but the first one 20 years ago, I can remember or more than 20 years ago when captopril introduced into the treatment of heart failure.

Slide 13

Now this one came in with pulmonary oedema, acute renal failure as you can see here high serum creatinine and he was known to have LV dysfunction because of an MI before. When the history was elucidated, it was found that before the actual admission to the hospital he had already 2 other episodes of increases in serum creatinine every time when he got an ACE inhibitor.

Slide 14

Now, then only after the third episode people looked at the renal arteries and there was bilateral artery stenosis.

Slide 15

Which was corrected with a stent.

Slide 16

So in this case easy and thereafter he sustained the ACE inhibitor treatment which was needed for treating his congestive heart failure. Showing this because it’s an example which we sometimes do not look at too closely because those patients come along with normal blood pressure and even low blood pressure and not high blood pressure. I’ve indicated before the prevalence of renal artery stenosis with coronary disease.

Slide 17

Now the question then arises is it useful to screen every patient in which a coronary angiogram is done for renal artery stenosis? I don’t think it is not and the American Heart Association and the American College of Cardiology had a committee working on that and they’re saying that angiography during coronary angiography, renal angiography should only be done when there are people that are potential candidates for revascularization.

Slide 18

That’s evident but who is a potential candidate for revascularization? The RCTs that we have there are 4 or 5 that compared intervention with medical treatment did not demonstrate the benefit of revascularisation versus medical therapy and there is significant morbidity associated with intervention. So I always do not recommend in a patient that is otherwise well treated and has no problems with his blood pressure or with his renal function to look at the renal arteries when the coronary angiogram is done. I also want to point out that when we consider invasive treatment of people with renal artery stenosis, we should have in mind that those people are very sick people especially if they have cardiac disease at the same time. So we shouldn’t expect too much benefit from any intervention because the people are just very sick.

Slide 19

In one study with the prospective follow up of about 100 people with renal artery stenosis and of the hospital Doctor Kalra is coming from it was found that after a mean follow up of two and a half years more than1/3 were dead and ten further % were on dialysis. Another study with 200 people similarly with their renal function and age after 4.5 years 24% were dead, 11% on dialysis and in a further study similar data. So those are even at an age which is not very advanced, mid 60s survival times of 5, 6, 7 years that’s a very sick population and I doubt whether big changes can be induced by PTA or any other means. Whether this is true or not it’s only my opinion will be shown by the CORAL study which is now running in the United States.

Slide 20

My conclusion is screening for renal artery stenosis in all people with coronary disease or congestive heart failure or undergoing angiography is not indicated. Screening in the above should be restricted to those with a decrease in GFR with inhibition of the renin system for treatment of hypertension or for heart failure even if they’re normotensive, those whose flash pulmonary oedema, with drug resistant hypertension and for the rest just wait for the results of CORAL within the next 2 years.

Slide 21

Thank you for your attention.

Slide 22

Chairman: Thank you very much Doctor Mann. So the paper is now open for questions. Doctor Mann maybe I could just start? Just about the CORAL study I’m sorry being the lead nephrologist for ASTRAL which has finished I have to say something about and I think Doctor Goldsmith will as well but this ASTRAL actually includes 800 patients and we finished recruiting in April and it will be published next year. We won’t specifically be looking at the heart. That’s the key point you’re making but I think CORAL is seeking to recruit 1000 patients and there are 220 after 2 years I spoke to Doctor Cooper quite recently so it’s going to be many years before they get the answer from CORAL.

Dr Mann: Yes that’s a problem and I think either a problem with the patients or with the doctors who believe that the cosmetic correction of a stenosis is something positive for the patient I mean it’s easy to convince a patient there’s such a narrow stenosis so I just go in and blow it up and then you will be 20 years younger. Easy but wrong.

Chairman: I think you’ve got a question thank you.

Question: Your conclusions are rather conservative. Does it make a difference to you if the patient has got a bilateral stenosis or if he’s got a stenosis in a single kidney?

Dr Mann: No it doesn’t make a difference whether there’s a bilateral stenosis or a single kidney. Those with a bilateral stenosis are prone to more severe consequences and they more often have impaired renal function so if there is severe renal impairment of renal function I would opt for treating him especially if GFR is decreasing. If somebody has a unilateral stenosis and has severe impairment of his renal function I would not touch on the renal artery as a rule.

Question: What is in your experience the frequency of complications of --- of this kind of intervention, cholesterol emboli, atherosclerotic emboli and so on?

Dr Mann: Doctor Bernheim reported problems of intervention let’s say PTA are not negligible, are major problems in the range of 5-10%, if you include rather large haematoma and pseudoaneurism mortality in the range of 0.5% as a consequence of the disease, cholesterol embolism 0.5-2% depending on the study but that’s certainly under reported. Some patients come under dialysis directly after intervention, it’s not 0.

Chairman: Just whilst we’re waiting for the microphone Doctor Mann. There seems to be a growing interest certainly amongst cardiologists about the possibility of screening for cardiovascular disease in patients with congestive cardiac failure and one or two anecdotal reports that improving the renal arteries with RAS and CCF might actually benefit the patient. Have you any views on that at all?

Dr Mann: I didn’t show the data I know of one study that looked at 100 consecutive patients with congestive heart failure who underwent coronary angiography to see whether ischemic cardiac disease is the cause of congestive heart failure and 7 or 8 patients had severe renal artery stenosis with normotension. So that’s about the number. The study by – is from the late 80s. I didn’t find any other report, probably I didn’t find it but I couldn’t find any other report of consecutive patients looking at this question.

Chairman: Thank you.

Question: There are cardiologists that not only look at the renal artery when they angiograph the coronary arteries but they actually stent up or they balloon up and then stent up the arteries in the same sitting. They’ve got enough --- to do these sort of things. What I’m trying to say is that I think you’re in the wrong place, you should be addressing the cardiologists and not the nephrologists.

Dr Mann: I mean they are stenting a lot of things which look at the study --- that has just been published comparing conservative treatment for coronary disease in stable coronary disease with intervention, no difference in outcomes. They also do stenting of the coronary arteries within the same intervention if the patient consents and you can do it. There are various incentives in various countries to do it or not to do it, some of which are also money.

Chairman: Ok well thank you very much indeed Doctor Mann and for keeping the time, that’s excellent.