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Prof William E. Mitch
President, American Society of Nephrology Edward Randall Distinguished Professor of Medicine University of Texas Galveston, TX , USA |
Prof Zoccali: You are the President of the ASN. The ASN is the largest scientific society in the field of Nephrology. It has an ever increasing international flavour and Renal Week is in the agenda of most nephrologists worldwide. Do you have specific projects to make your society even more internationally orientated than its is now?
Prof Mitch: The charter of the American Society of Nephrology (ASN) is for North America and, hence, includes Canada, Mexico, Central America, Caribbean countries and the United States. This year we have instituted a grant program in conjunction with SLANH (Sociedad Latinoamerica de Nefrologia y Hipertension) to interact more closely with young nephrologists both from other areas of North America and from South America. Recipients of these grants will spend a month with a Division of Nephrology in the U.S. or Canada and then attend Renal Week, the ASN Annual Scientific and Clinical Program. Secondly, Dr Robert Narins, ASN Director of Postgraduate Education, has constructed 1 day “Regional Meetings” that are held in different parts of the U.S. At these meetings, highlights of Renal Week are summarized, reviewed and critiqued for ASN members and others who were unable to attend Renal Week or who missed key presentations. The ASN Council has discussed whether a similar program might promote interactions with our international colleagues. We would like to strengthen the many clinical and scientific ties between the ASN and other nephrology societies.
Prof Zoccali: One important aspect of the ASN is its lobbying activity with the Congress. This issue is at center stage in the ASN newsletter. To me other societies have much to learn from the ASN in this area. Could you please tell us the main advantages and the benefits which have derived to American Nephrology from this well conceived, continuous lobbying activity?
Prof Mitch: The ASN represents the common interests of both nephrologists and scientists who are interested in kidney disease so, in that sense, we are a “lobby”. However, we believe that the most effective way of influencing Congress is to bring to their attention advances in kidney research or problems that are faced by nephrologists, and our strategy is to highlight specific scientific and clinical issues for members of Congress and the National Institutes of Health (NIH). About 5 years ago, the ASN, in conjunction with NIH leaders, surveyed areas in kidney disease that needed intensive research and wrote a “Research Priorities” booklet which has assisted the NIH in identifying priorities for research investment. This year, we are holding similar meetings with nephrologists, as well as scientists outside of nephrology, but we will address only 5 areas: acute renal failure, hypertension, diabetic nephropathy, transplantation and uremia. The plan is to identify topics in each area that are ripe for research investment. Regarding the practice of nephrology, ASN members have written a “white paper” for Medicare that reviews positive and negative aspects of new regulations on dialysis reimbursements. In short, we believe that highlighting specific issues is the most effective way to influence Congress and the NIH.
Prof Zoccali: Muscle proteolysis/wasting is one of your main interests and you have offered fundamental contributions in this area. Do you foresee scientific advancements (on this topic) that may soon hit the clinical arena?
Prof Mitch: Recently, we found that activation of caspase-3, an intracellular enzyme of the apoptotic pathway, is an initial step causing loss of muscle protein (J. Clin. Invest. 113:115, 2004). This is of interest because this initial step leaves a “footprint” of capase-3 activity in muscle, a characteristic 14 kDa fragment of actin. Although we have not yet studied patients with kidney failure, we have found this footprint in muscle biopsies of patients with accelerated muscle atrophy from aging or burn injury and, importantly, it disappears with effective therapy. We speculate that finding this fragment could develop into a simple method of identifying that a patient has accelerated muscle protein breakdown and, if countermeasures to block protein breakdown were successful, the actin fragment footprint should disappear. Clinically, this needs to be tested rigorously so it could be added to aggressive treatment of metabolic acidosis in order to prevent the loss of protein stores.
Prof Zoccali Dietary treatment of CKD is another area in which you have offered important methodological and experimental contributions. Do you think that this is still an area needing further research? What studies are you presently pursuing or perceive as much needed?
Prof Mitch: I believe that attention to diet is a critical part of successful treatment of patients with chronic kidney disease (CKD) as well as dialysis patients. Regardless of opinions on whether dietary manipulation slows progression of renal insufficiency, CKD patients have a limited ability to excrete the waste products that cause uraemia as well as sodium, phosphates, etc. A properly designed diet can prevent the problems arising from impaired excretory capacity in addition to the other metabolic problems of CKD patients. The importance of a proper diet for CKD patients is recognized in the U.S. by Medicare, as they now pay for dietary consultations for CKD patients. The more pressing problem, however concerns worldwide projections of the growth of kidney disease. Nephrology must find ways of ameliorating the problems of CKD patients besides dialysis. The economic and physician resources to treat all these patients with dialysis are simply not available.
Prof Zoccali : Do you think that, as occurred in the early days of dialysis, the epidemics of ESRD may eventually impose hard choices also on affluent countries and eventually bring back the ethical dilemma of making choices about who should be treated?
Prof Mitch: I fear you are correct because there will be pressing economic and manpower shortages. Besides continuing our efforts to find measures to eliminate kidney disease, I believe Nephrology must take the lead in designing a complete therapeutic program for CKD patients. The program should include a diet that assists in the control of blood pressure, blood sugar and the accumulation of unexcreted waste products, the use of inhibitors of the renin system, and attention to factors that cause cardiovascular disease.
Prof Zoccali: How do you foresee nephrology in 2015? What kind of organizational, technical and scientific evolution do you envisage in 10 years' time?
Prof Mitch: I find it very difficult to predict the future because of the rapid expansion of patients at risk for diabetes, of patients with diabetic kidney disease or other nephropathies. Presently, we have very few programs directed at identifying patients who are at high risk for CKD early and enrolling them into a preventive program. I only hope that nephrology will be heavily involved in making decisions about methods for identifying and treating CKD patients. For this to occur, it seems to me that nephrologists must quickly take a leading role now in designing programs for combating the epidemic of CKD.
Prof Zoccali If you received an invitation from congress to spend 100 billion dollars for a research project that you consider as being of immediate (or almost immediate) use to patients with CKD, which project would you propose? (I know that this is not easy, but please try.)
Prof Mitch: This is a very difficult question because I fear that the epidemic of CKD will be upon us before key discoveries are made about preventing and treating kidney disease. For this reason, I believe major funding should support research into basic mechanisms for the problems of kidney disease. My confidence in research is bolstered because even relatively recent reports have been translated into clinically useful strategies (e.g., the ability to use molecular techniques to mass-produce erythropoietin and the discovery of the calcium receptor leading to calcimimetic agents that can control hyperparathyroidism). Beyond research of this type, efforts should be made to determine accurately how many individuals are at risk for CKD.
Prof Zoccali: How did you become interested in renal diseases? How important were your mentors in your choices?
Prof Mitch: When I was a medical intern and resident, John Merrill and his colleagues were introducing treatments for CKD patients who previously had had no hope of leading a productive life. The excitement of implementing these new strategies and the obvious opportunities for research in several distinct areas of nephrology made it the obvious career choice. Likewise, opportunities for advancing patient care through biomedical research were emphasized daily by George Thorn and Eugene Braunwald and this created an atmosphere at the Brigham that was impossible to avoid - every one of my class of residents wanted to participate in this excitement.
Prof Zoccali: Which scientific papers influenced you most?
Prof Mitch: There would be a long list for two reasons: first, important discoveries almost invariably raise questions that have to be answered by future experiments. This makes it difficult to pick one paper about a topic; and secondly, my interests became broader with time. When I began in nephrology, I was intrigued by a chapter on intracellular mechanisms of protein degradation (Annual Review of Biochemistry 43:835, 1974) by Fred Goldberg and Paolo Dice. Then there was the initial article about changing urea metabolism with ketoacids by Mack Walser (J. Clin. Invest. 52:678, 1973) plus the evaluation of protein intake in dialysis patients by M.F. Borah and others (Kidney Int. 14:491, 1978).
Prof Zoccali: What is your favourite hobby?
Prof Mitch: Listening to classical music, especially Bach and Scarlatti, plus tennis.
