Interview with Dr Kerstin Amann

Dr Kerstin Amann Institute for Pathology University Erlangen-Nurnberg Erlangen, Germany

Zoccali: Your paper on nephron number in patients with primary hypertension (New England J Med 2003; 348.101-108) is a landmark step in the quest of testing Brenner’s hypothesis on the renal origin of hypertension and progressive renal damage. How did the idea of testing this hypothesis originate in your laboratory?

Amann: The idea was born at the beginning of the 90ies when Barry Brenner presented his fascinating theory at some international meetings which Prof. Ritz and I attended. We then reasoned about a study setup that would allow us to measure glomerular number in hypertensive compared to normotensive patients. In parallel, new stereological techniques were developed in particular by Gundersen and Nyengaard and published. These techniques enabled us to investigate a greater number of human kidneys and thus the idea became much more attractive.

Zoccali: How much time has this particular research project taken?

Amann: As mentioned above we started in 1991/1992 with talking about the study design and discussing the project with our partners at the Department of Forensic Medicine and Pathology. We then studied the new stereological techniques, in particular the fractionator technique, in animal models and compared it with our standard techniques. We then had to adapt the method for the use in human kidneys (which again took some time). Even in cooperation with the Dept. of Forensic Medicine it was not easy to identify enough cases (who met the inclusion criteria) and matched normotensive controls. Several medical student and coworkers from my group tried very hard, but only when Dr. Keller started her doctoral thesis several years ago the project really made progress and came to an end.

Zoccali: The difference between hypertensive patients and matched normotensive controls in your NEJM paper is very impressive. Is there any additional verification that you may envisage to strengthen your otherwise very convincing findings?

Amann: The differences are indeed striking and this is true for all parameters that we investigated. Not only nephron number and mean glomerular volume were significantly different, but also histological indices were markedly different between the two groups.

Zoccali: In discussing your findings in the NEJM paper you allude to Barker’s hypothesis and to fetal programming. Do you believe that intrauterine life is more important than the genetic background in determining hypertension and the predisposition to renal function loss?

Amann: First, I would like to emphasize that for logistic reasons we could only investigate a small group of subjects; thus, it is not possible to extrapolate from our data on essential hypertension in general. Our findings do not exclude at all that there are other ethnical or racial groups with hypertension that do not show these alterations.
Second, I believe that essential hypertension represents a mixture of genetic back-ground and environmental influence. Our study points out, however, that it is important to emphasize the possible involvement of genes other than the usual candidate genes (i.e. vasocon-strictors and vasodilataros). Alterations in developmental genes during intrauterine life could very well be involved in the pathogenesis of hypertension and this view may open completely new perspectives.

Zoccali: Due to the accidental nature of death of patients and controls no data about renal function were available in your study. Is there any way to have information on the link between nephron number and actual renal function in vivo in man?

Amann: Not to my knowledge, but since I do not really know much about possibilities of measuring renal function you`d better save this question for a nephrologist.

Zoccali: Do you have other parallel research projects aimed at testing Brenner’s hypothesis?

Amann: We are currently discussing some follow-up projects together with the local colleagues from the Dept. of Nephrology and Pediatric Nephrology at Erlangen and hope that we will be successful in developing new experimental and clinical studies.

Zoccali: Which is the main implication of your findings in terms of prevention of cardiovascular risk and renal failure?

Amann: I think we are far away from preventing cardiovascular risk and renal failure. It would be naively simplicistic to believe that there is one single cause of essential hypertension. It is by no means excluded, and positively very likely, that other (functional) abnorma-lities are also relevant in causing or aggravating hypertension.
Together with the available animal data, however, our study in humans may provide some additional insight into one possible pathogenetic principle of the development of hypertension in one particular group of patients and the important role of the kidney in this process. If we can identify environmental factors like for example nutrition we may develop new therapeutic strategies. But again, there is a very long way to go !

Zoccali: Do you think that women need to have more research opportunities than they have now?

Amann: This is difficult to answer because I think this depends very much on the individual and the personal way of style.
As far as I was concernded I was always lucky to have great support from my chiefs and in particular from Prof. Ritz and Prof. Mall. Therefore, I could do most of the things I wanted. It was and still is, however, sometimes very difficult to bring together the clinical routine of beeing a pathologist and the interest in research, in particular if it comes to beeing away very often for congress reasons, etc. But this is of course the same problem for men and women. There are, however, some collegues who have problems with women in research, but -thanks God- they are a minority and therefore do not really count.

Zoccali: Could you tell us which problems you encountered in your career?

Amann: There were never real problems, only important decision to make.
I think that probably the most important point in my career was the decision to become a pathologist. Initially I started as a surgeon and later on spent one year at the Department of Cardiac Surgery of the University of Heidelberg. Luckily, Pathology and becoming a pathologist was more attractive, however, thanks to my mentors Prof. Mall and Prof. Ritz, and so I continued with pathology. The next crucial step was definitely my move from Heidelberg to Erlangen to become a full professor of nephropathology. And this was only possible because the local renal research group (the so-called Sonderforschungsbereich) was founded under the leadership of the late Prof. Sterzel.

Zoccali: Renal research apart, which is your favorite hobby?

Amann: My favourite hobby is sports in general and in particular Judo which I have practiced for more than 30 years now and where I am also an international referee.