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Prof
Francesco Locatelli ERA-EDTA President Director, Division of Nephrology and Dialysis Alessandro Manzoni Hospital, Lecco, Italy |
Zoccali: The ERA-EDTA is the second largest Nephrology society in the world. Which are the main challenges of our society today and the near future?
Locatelli:
The ERA-EDTA is a healthy society. In the last five years, we have reached a
stable number of members (more than 5,500), while participation to our annual
Congress is constantly increasing (we had about 5,000 delegates last year in
Copenhagen, with a record number of submitted abstracts). Thus, the main challenge
is also the most obvious one, which is the advancement of scientific culture.
We are planning new initiatives in order to encourage young doctors and researchers
to improve their knowledge and skills. New initiatives and a continuous renewal
are essential to an Association as they are to a living organism, because they
help preventing the natural decay. We should have a research programme founded
by our Society. However, the organisation of this programme is quite difficult.
Probably our Society should have very well defined fields of interest and some
free topics, but it is a little bit too early to discuss this aspect that should
be firstly further examined by the Council.
We should be aware that, also from the Nephrological point of view, Europe is
not a homogeneous country. We have very high-level centres around Europe with
top researchers and clinicians who can compete with the Nephrology centres of
the United States; on the other hand, we also have Nephrologists operating in
centres that, mainly because of socio-economical reasons, need more educational
activities than high-level congresses or seminars. Thus, the most frequently
asked question is: should our Society compete with ASN or should we be closer
to the more general approach of ISN? Bearing in mind that ERA-EDTA has at least
two souls, the challenge is how to harmonise these differences. During our congresses,
we have to organise the scientific programme taking into account the different
needs of our attending Nephrologists and, more in general, of European Nephrologists.
The naive answer could be that, as we have these two souls, we should organise
the annual congress of our Society in order to satisfy these completely different
scientific expectations. Thus, in my opinion, we should have a high-level congress
able to attract as much as possible the participation of the most active and
outstanding Nephrologists from all over Europe (and, let me say, they are numerous
if we consider their active participation at ASN Congresses and their papers
published in the most outstanding journals), but also to possibly attract people
from outside Europe. In this way, we could really compete with ASN, and make
our relationship with them even easier, possibly by organising together some
symposia or initiatives on specific topics of common interest, like guidelines.
In this respect, I have very much appreciated the initiative of Gary Eknoyan,
together with Nathan Levin and Adeera Levin, to start a new co-operation among
K/DOQI Guidelines, European Best Practice Guidelines, and other countries with
initiatives about guidelines around the world. The first meeting of the so-called
“Global Guidelines” was held in London last January and it was a
great success, all the participants were enthusiastic of this project. Therefore,
we should congratulate our colleagues for this foresighted initiative, but,
let me underline, this is only the starting point. It is well known that it
is by far more difficult to carry over, and successfully conclude, these activities
than to start them.
On the other hand, we should not forget the needs of many Nephrologists from
various countries around Europe. Therefore, during our annual congress we should
organise Educational Courses in different languages, according to requests (and
possibly anticipating them).
In our Society, we also have the tradition of organising educational activities
around Europe. This programme has been developed by Eberhard Ritz and we should
congratulate and thank him for the great success of the initiative. Now the
programme is continuing under the responsibility of Andrzej Wiecek, with the
support and expertise of Eberhard Ritz, and I believe that it is to be maintained
and possibly further developed. However, I also believe that the time has come
for our Society to organise top seminars in different fields of basic science,
clinical nephrology, dialysis and transplantation. It doesn’t matter in
which part of Europe they will be held.
The separation between basic science and clinical activities is a big mistake.
We need to integrate one with the other, to give a rationale to clinical research
and a concrete aim to basic research. While wishing this integration, we should
not forget that the large majority of Nephrologists are clinicians who are taking
care of patients in everyday clinical practice; thus, in order to satisfy their
needs, our activities should be mainly clinical-oriented.
Another important aspect is the relationship with other Scientific Societies.
We should improve it by organising common activities, not only congresses and
symposia, but also educational activities, guidelines and researches. This co-operation
is of paramount importance for increasing our knowledge and looking at problems
from different points of view.
The Registry is another great success of our Society. I am very happy with the
new Registry in Amsterdam and I would like to thank Douglas Briggs for his wonderful
and dedicated job. I am also very confident that under your Chairmanship, Carmine,
and with the expertise of the Amsterdam team chaired by Kitty Jager, the Registry
will be able to give us very important information..
By the way, I would like to Tilman Drüeke, all the team of NDT-Educational
and yourself for your wonderful job. I have received many congratulations for
this new educational activity of our Society and I’m very proud of this
success. Furthermore, we don’t have to forget that NDT is a journal of
increasing importance, very well recognised and quoted around the world, as
indicated by its increasing impact factor, and that it is self-supporting from
the economical point of view. This has been possible thanks to the activity
of the previous Editors-in-Chief, Sandy Davison and Eberhard Ritz, and the present
Editor-in-Chief Tilman Drüeke. Let me say that a journal is the mirror
of the health of a society. Thus NDT and NDT-Educational are the mirror of the
wonderful health of our Society, with its two souls: the scientific and the
educational one.
I would like to thank all the Past Presidents, and the Secretary-Treasurers,
the Chief-Controllers, in particular Vincenzo Cambi, Fernando Carrera and Luis
Piera, the Chairmen of the Paper Selection Committee and the Members of the
various Councils, who have contributed to the present success of our Society.
I would also like to thank Rosanna Coppo for her wonderful job on CME.
Putting all together, our main challenge is trying to maintain and possibly
increase this success. However, I’m very close to John Fitzgerald Kennedy
when I say that the members of our Society shouldn’t ask what the Society
does for them but what everybody is doing for the Society.
Zoccali: Clinical Medicine has entered into an era of profound
transformation. The restructuring of roles of doctors and other health workers,
the tantalizing increase in overall cost of health system, and very near advent
of clinical genetics and pharmacogenomics, are areas where changes seem to be
particularly problematic. How these problems will impact on Nephrology?
Locatelli:
As a part of Clinical Medicine, Nephrology has been rapidly changing
in the last decades. Once seen as a temporary means of rescuing individuals
from uraemic coma, dialysis has now become the standard renal replacement therapy
(RRT) and thousands of people with irreversible uraemia can now live for many
years. As a consequence, the characteristics of the dialytic population have
substantially changed over the past 30 years, becoming older and older with
a greater number of coexisting diseases. However, in spite of the fact that
considerable evolution in treatment modalities has lead to a significant increase
in the efficacy and tolerability of dialysis, the achieved survival in RRT patients
is still too low and their quality of life rather poor. Cardiovascular disease
is the leading cause of death. Mortality in patients with chronic kidney disease
and the reduction of the burden of cardiovascular disease in our patients are
among the major challenges Nephrologists have to face today. Another major challenge
in the field of Nephrology is the observed increase of the number of patients
with diabetes and diabetic nephropathy all over the world. This, which has also
been defined as “a silent epidemic”, will probably have a major
role in the foreseen imbalance between the limitation in the increase in overall
cost of health system and available facilities and funding to manage these patients.
Molecular biology, genetics and pharmacogenomics are very fast evolving fields
with a large impact on Nephrology. These new approaches have lead to a substantial
revolution of knowledge, even if sometimes they make hard life for physicians
to remain up-to-date! In my opinion, these approaches have allowed the understanding
of a substantial number of cause-effect relationships among genes and the correspondent
pathology. However, the impression is that we have discovered almost all the
pieces of the puzzle, but we still need something more to put them all together
to have a comprehensive and unitary view of the phenomena.
Zoccali: Do you think that, in Europe, Nephrology as specialty is considered less attractive than it used to be 10 years ago or so?
Locatelli:
I don’t think so. Certainly, in Italy, for example, the number of new
fellows in the field of Nephrology has markedly decreased in the last decade,
but this is mainly due to a restriction in the number of available places for
the fellowship and not to reduced interest. We need more information about the
situation all over Europe, but the increasing number of attendees coming to
our annual meeting, although more and more coming from Eastern European countries,
seems to state against this point.
Continuous technological advancement in the field of dialysis has greatly differentiated
our speciality from conventional internal medicine, giving to Nephrology a unique
feature. Nephrology has been growing and developing through sophisticated technology
and deriving some expertise from surgery and interventional medicine. All these
aspects have been integrated in a new approach, in which the patient is considered
the core. The combination of these two souls, humanitarianism and technology,
is a hard challenge we have to face, that requires commitment and sacrifice,
study and research capability, but also humane endowments.
Research has reached impressive advancing in recent years. However, what the
future is promising us is even more fascinating. In the field of dialysis, biofeedback
and telematic-dialysis will make the treatment more and more safe, automatic
and efficient, by paradoxically increasing medical and nurse surveillance even
from the distance. The theoretical possibility of also automating vascular accesses,
thus avoiding repeated injections, and the realisation of a dialysis machine
with nearly complete reduction of initial preparation and final sterilisation,
the so-called “one button machine”, will lead towards a much more
widespread use of home daily hemodialysis, which is more physiological and rehabilitating
for patients. Other rapidly evolving field are those of genetic engineering
and the use of staminal cells. We hope that these two new approaches will give
us in the next years important clinical applications, especially in the early
prevention of nephropathies, well before patients have reached chronic renal
insufficiency and the need of RRT.
Zoccali: In Europe there is an increasing interest on basic
research. Do you think that clinical research receives scarce attention from
national health systems and more in general by funding institutions?
Locatelli: Unfortunately, it is a matter of fact that, in spite of growing interest on basic science and clinical science, national health systems and funding institutions do not support them enough. This is partially due to a limitation in available funds to assign, but it also probably reflects a lack of knowledge, at political levels, of the true importance of scientific research in the process of development of every country, even if results do not have immediate economic relevance. As a consequence of this limited funding by national health systems and funding institutions, the link between research and pharmaceutical companies is becoming more and more strict. We still don’t know what the final effect of this process will be, but we certainly run the risk of losing some of the independence of research from economic relapse: by definition, knowledge for itself can not exist in the business world. Of course, this is not only a problem of the ERA-EDTA, but it could be a good reason to try to have an independent programme of research founded by our Society. On the meantime, I would like to thank the industry for their continuous support to our Society, allowing us not only to organise our annual congress, but also all our activities without any pressure.
Zoccali: The growth of Nephrology in Eastern Countries is very impressive
indeed. What are the programmes of the ERA-EDTA for supporting Nephrology in
Eastern Countries?
Locatelli: The ERA-EDTA has done a lot of work in the past to promote Nephrology in Eastern Europe, and more will do in the future. Every year we organize several seminars and courses in these countries with well-known experts for every field of Nephrology. For example, the Budapest and Prague schools are a big success. Besides, doctors from most Eastern countries still pay a discounted membership fee, thus they can receive our Journal for a very small amount of money. Nowadays medical knowledge is developing and spreading mainly through the Internet, and it will do this more and more in the future. For this reason, a resource such as NDT-Educational is very helpful and will make the link between Eastern Europe and our Society even tighter.
Zoccali: It seems that British Nephrology and Nephrology in
some Northern Atlantic countries participate to the life of our society less
than Mediterranean countries. Is there anything that can be done to increase
the participation of these countries to activities of the ERA-EDTA?
Locatelli: It is a fact that every year only few colleagues from these countries attend our Congress but I would not speak of scarce interest in the Association. We have quite a good number of members of our Society coming from the United Kingdom (fourth country in Europe, and this number has always been increasing in the last ten years). We also don’t have to forget that we receive many contributions to our Journal from these countries.
Zoccali: Your clinical research interests are wide ranging
and span from dialysis technology to renal registries and progressive renal
diseases. Which is, at present, the research topic at the top of the list in
your mind?
Locatelli: I am involved in a number of prospective, randomised, multicentre, clinical trials about outcome of patients with chronic kidney disease on dialysis or in the conservative phase and about treatment of anaemia. I’m cooperating with the DOPPS study team and I am chairing the Membrane Permeability Outcome Study (MPO) (we could discuss it later), and a study about acetilcysteine capability of reducing oxidative stress in CKD. Moreover, we are evaluating drugs for controlling phosphate retention and calciomimetics. Finally, I’m conducting epidemiological studies on cardiovascular complications and malnutrition and I am also the coordinator of a trial about adding azathioprine to steroids for slowing down the progression of IgA nephropathy.
Zoccali: How do you manage to combine your research and managerial
duties of President of a major International Society and a large National Society
and of Director of one of the largest Nephrology departments in Europe?
Locatelli: I really could not manage it if I did not work from early in the morning until late in the evening. It is difficult, with so many commitments, meetings to attend, researches to plan, papers to write and review , but luckily I can rely on a very good team of excellent co-workers, dedicated secretaries and an understanding wife. Moreover, the Council members of our Society are helping me very much and let me particularly acknowledge the help of our Secretary-Treasurer, Jorge Cannata-Andia and all the members of our Administrative Office in Parma.
Zoccali: You are the leading investigator and chairman of an
ongoing study currently being performed in Europe to test whether high flux
dialysis may reduce mortality as compared to low flux dialysis. Do you think
that the results of this study are now particularly important also in light
of the methodological shortcomings (high proportion of patients previously treated
with high flux dialysis and high average kt/v at enrolment) of the HEMO study
that you have recently pinpointed?
Locatelli:
Despite the large sample size, the HEMO Study unfortunately failed to demonstrate
any benefit on survival of either high dialysis dose or high-flux membranes.
In my opinion, these disappointing results are not fully unexpected and could
be partially explained by demographic and dialytic characteristics of the patients.
Participants in the HEMO Study were not fully representative of the US composite
haemodialysis population (mean age was lower and percentage of African-Americans
was higher compared to the US HD population).
A selection bias was also evidenced by some dialysis-related parameters. At
baseline, the delivered dose of dialysis was high (mean eKt/V of 1.43) and high-flux
dialyzers were used in more than 60% of the participants. Furthermore, at baseline
time on dialysis was relatively long (3.7 years), indicating a selection of
fitter patients with longer-survivals.
Hence, overall the HEMO Study sample was not representative of the US haemodialysis
population as a whole and by definition of the European dialysis population.
Considering patient characteristics at baseline (high mean Kt/V, high proportion
of patients treated with high-flux dialyzers), it is likely that a carryover
effect occurred after randomization. Some of the patients who had been previously
treated with high-flux membranes were likely to be randomized to the low-flux
arm. Similarly, some of those who have had high Kt/V at baseline were randomized
to the standard-dose group. This might have led to a confounding effect and
to a bias in the final results.
Another factor that might have led to a misinterpretation in the comparison
of high-flux vs low-flux membranes is the reuse of dialyzers. Although commonly
practiced in the US, reuse affects high-flux membranes performance and the practice
of reuse might have led to loss in permeability of high-flux membranes, which
could have been similar to low-flux dialyzers in a final analysis.
Thus, it cannot be excluded that a higher dialysis dose target for the high-dose
arm might have led to beneficial effects on survival. However, it is almost
impossible to increase dialysis doses without modifying the frequency. At present,
short or long nocturnal daily dialysis have limited diffusion, even if results
are very impressive, but the general applicability of this approach is questionable
without solving the problem of the “one button machine”, vascular
access and reimbursement.
Moreover, participants in the HEMO Study were prevalent haemodialysis patients.
Thus, dialysis history prior to the time of randomization and selection of long
survivors might have affected these results. Since the study was aimed at strictly
evaluating the effect of treatment modality to which patients were randomized,
any effect from previous dialysis schedules should have been ruled out. This
would have been easily achieved if only incident patients had been included.
The magnitude of the problem is of clinical relevance considering that the mean
time on dialysis was of 3.7 years and that the mean follow-up time was definitively
shorter (2.84 years).
The MPO (membrane permeability outcome) Study, which is underway in Europe,
was designed to prospectively evaluate long-term effect of membrane permeability
on clinical outcomes (including mortality, morbidity, vascular access survival
and nutritional status). The length of follow-up will be of three to six years.
Only patients who have been on dialysis for no longer than two months (incident
patients) are included. This policy was chosen to rule out any effect from previous
treatment schedules and to allow the investigators to evaluate only the effect
of flux on outcome. We decided not to evaluate the effect of different doses
of dialysis, according to our previous experience that it is difficult to have
beneficial effects on survival by further increasing the dose of dialysis when
baseline dialysis dose is already adequate according to the present general
agreement. Thus, after the publication of the Hemo Study, results from the MPO
Study are awaited with much interest. Of course, I agree that a possible beneficial
effect of convection could be attenuated by the fact that its level is low in
high flux dialysis and only haemofiltration and particularly haemodiafiltration
could provide a high dose of convection together with a powerful clearance of
low molecular weight substances.
Zoccali: We know that you are a football fan. Is it true that
your ambition is to coach Atalanta football team?
Locatelli:
I was born in Bergamo. From the very early days, I have been a supporter of
the local team, Atalanta, together with my nine brothers and sisters! Of course,
according to the Italian tradition (but probably not only the Italian one!)
every supporter wishes to be the coach of his own team and possibly of the national
team too! (I have a dream………). This is a way to remain a child
forever and to have an escape from everyday routine activities. Walter Hörl
often makes jokes about my supporting Atalanta (not a very strong team, let
me say). But I’m not the only football fan among Nephrologists! As you
well know, Carmine, every Sunday I am used to exchange e-mails with you, supporter
of Reggina (the team from Reggio Calabria) and with Giuseppe Maschio, former
supporter of Verona, and now supporter of the small, fantastic team of Chievo-Verona,
about the results of our favourite teams. We just joke and smile and this is
important in this hard life!
