Interview with Prof C. Wanner

Prof C. Wanner Department of Medicine, Division of Nephrology University Clinic Würzburg, Germany

Prof Zoccali: You are the director of an academic renal unit with several research projects both in clinical and basic science. Which is the main difficulty for being successful in both areas?

Prof Wanner: Strong efforts have to be made to guide a renal unit towards a good balance between the necessity of patient care and the interest in good research projects. A lot depends on the co-workers the unit can attract. Difficulties for the balance emerge when the shift of resources towards routine patient care is too strong. Considerable energy is necessary to defend, often in the interest of the co-workers, protected lab time from the daily demands the clinic has. I believe that a balance can best be achieved by carrying out results from basic science (bench) directly to clinical projects (bedside). Years ago, I was lucky to convince Jan Galle to join the group. He is successfully running the basic science lab where many of our key young people have made their first steps.

Prof Zoccali: Perhaps cardiovascular complication of chronic renal diseases is your favourite subject. How did your interest in this topic start?

Prof Wanner: This interest originated 15 years ago out of the lipid field when Heinrich Wieland, who ran a first class lipid laboratory at the University of Freiburg, invited me to use a beautiful high throughput diagnostic technology park. However ultracentrifugation machines produced results of difficult interpretation and even a stable isotope technology training at the US-NIH during 1992 did not really solve my questions. Although the complex dyslipoproteinemia of the nephrotic syndrome and renal failure initially protected me from nasty questions such as “What does all that mean for the outcome of CKD patients”. Subsequently these questions appeared, but no big "statin company" wanted to invest money into cardiovascular outcome research of kidney patients at that time. When I moved to Wuerzburg in 1994, I discovered Franconia with dialysis centres tightly linked to the renal unit at the University hospital. These units cared for several hundred patients available for cross sectional observation studies with long-term follow-up. Colleagues were open to collaboration and we started the inflammation study with C-reactive protein as one predictive outcome marker in 1995. Except for that study, which originated from a clear hypothesis and was funded with a very small grant within the University, all other cardiovascular outcome research subsequently performed have always been influenced by "What is really feasable and can be done at a given time and with what resources". Unfortunately several good ideas could never be translated into research projects.

Prof Zoccali: The cost of clinical trials is very high and this is the main reason why they are rarely performed in patients with renal diseases. How would you solve the problem of having solid intervention studies in these patients?

Prof Wanner: Networking with dedicated collegues, on the multinational level, may at least provide the sufficient number of patients. Nevertheless, a limited budget is always mandatory. The 4D study was lucky that investigators expressed their clear willingness to solve a given hypothesis without remuneration. Sufficient funding was available from Pfizer for drug supply, insurance of patients, support groups, monitoring and organisation. Such an opportunity does not come along every day and pharmaceutical companies are the only supporters of intervention studies. Currently, the German government funding agency provides, for the first time, 50 Million Euro for clinical studies.

For nephrology I only see one solution. Funds, sufficient to embark in solid intervention studies, can be raised by national or international societies, from multiple sources, and distributed through foundations or charity organisations. The Nierenstichting in the Netherlands has been very successful so far.

Prof Zoccali: Do you feel that clinical epidemiology research in Europe is still a rather neglected area of research?

Prof Wanner: Clearly yes, the USA is way ahead and things are only slowly improving in Europe. I always wondered why so little is invested in this field. At least in Germany, reviewers and government funding agencies still believe that clinIcal research can simply be done by every doctor beside his routine clinical workload. This is certainly not the case since more complex epidemiology and cardiovascular outcome studies require highly trained specialists as well. Genetic field working units need clinicians trained in phenotyping of rare diseases, ideally with some knowledge in molecular genetics. Establishing a large scale biobank (serum, DNA and tissue) requires skilled technicians. Biobanks also need specific knowledge for establishment and a lot of care over time. On the other hand every national genome network initiative thoughout Europe is intensively searching for well characterized patient cohorts.

Prof Zoccali: You are now a member of the registry Committee of the ERA-EDTA and Editor of the Registry newsletter. We know that in Germany the ERA-EDTA Registry has a reputation that is inferior to its merits. What should the Registry do to gain credibility among German nephrologists?

Prof Wanner: Stepping into this new task I asked collegues why German nephrologists stopped sending data to the Registry in 1985. As often happens, communication had deficits at this time. This problem can certainly be overcome by more intense communication. Germany now has its own registry, the QuaSi-Niere, which came out during recent years. QuaSi-Niere is now very successful in collecting a growing database. I see that German nephrologists increasingly trust and believe in the work of QuaSi-Niere. This is not at all obvious in respect to the lack of remuneration quality assurance receives in Germany. Data collection is based on so-called good will and repeated collections for several Registries are not appreciated. I understand that my membership in the ERA-EDTA Registry may be useful in improving the communication between the various working groups. Currently, the ERA-EDTA Registry newsletter is a good initiative to demonstrate the work and the activities of the Amsterdam group to everyone.

Prof Zoccali: For a clinical investigator which is the best way for balancing clinical and research duties?

Prof Wanner: A clinical investigator requires the same amount of protected research time as any other basic science research person. Clinical investigators currently learn that the training and education slightly will be prolonged but usually they all take this task with enthusiasm. Colleagues should join working groups so that clinical studies can continue as well when the principal investigator him/herself has heavy clinical duties from time to time. Today many investigators join coordinating centers for clinical studies, which are established at most University hospitals and embedded in the medical faculty. Biostatistics, study nurses and capacity for surveys and monitoring can be shared. At the present time the group of secretaries, study nurses and doctors at our renal unit varies from 5 to 10 full time people.

Prof Zoccali: You are the chief investigator of the 4D study. The nephrology community has been waiting for the results of this trial for many years. Is there anything coming soon?

Prof Wanner: The 4D study started in February 1998 and was regularly closed in February 2004. The 4D study investigates the effect of atorvastatin on major cardiovascular events and outcome in 1254 type 2 diabetics on dialysis. Intense work is currently done to collect and evaluate laboratory data and more than 450 primary endpoints. According to a detailled plan unblinding will be this fall and data presentation subsequently at a major meeting most likely in November 2004.

Prof Zoccali: Which is the paper that influenced your scientific choices the most?

Prof Wanner: Back in 1983 I received a biochemistry and protein chemistry oriented research training in the laboratory of Walter Hörl. Transfer of data from the bench to bedside led to studies in nutrition, carnitine and lipid metabolism. In the neighbourhood of an excellent lipoprotein laboratory I came across John Moorhead and colleagues' groundbreaking hypothesis of lipid nephrotoxiciy in chronic progressive glomerular and tubulo-interstitial disease. (Lancet 1982;2:1309-1311). Since that time and with the help of good collaborators and friends I have followed the idea that lipids have an impact on progression of renal disease as well as cardiovascular disease. The field was broadened in cooperation with Jan Galle investigating lipoprotein derived inflammation and oxidative stress. Although Moorhead provided already some aspects at that time one question always remained "Is it really clinically relevant and can the lipid mediated pathology be treated". Following this idea one necessarily will end up doing randomized controlled trials.

Prof Zoccali: Which is your favourite hobby?

Prof Wanner: I believe that physical fitness goes along with a higher working capacity and better mental performance. Indeed some good ideas and projects always come to mind during cycling in Franconia and in other parts of Europe. Probably due to these activities my wife and three boys love outdoor activities and are good skiers. Unfortunately physical fitness requires at least 3 x 40 minutes training per week and I am intensively struggling to achieve that task. The goal/vision is to participate every year, in August, in a major cycling marathon in the Swiss Alps or in the Dolomites.

Prof Zoccali: Which advice would you give to a young fellow starting his/her career in nephrology?

Prof Wanner: If possible enter an active (!) scientific and clinical oriented group, where supervision by an inspiring mentor is available and a structured training can be provided. Our policy in Wuerzburg is to have talented students with us in our laboratory or in the genetic field service unit during the preparation of their thesis. If the student is willing and motivated to continue I would do first a one year intense clinical training and prepare for a two year research training in the field of interest. My advice would be to seek training in a molecular genetic lab. Hopefully the fellow will then come back to good old Europe and to your laboratory taking into consideration the current competition for little money and funding.