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2000 Presidential Address

2001; American Society of Nephrology; Volume: 12; Issue: 9 Linguagem: Inglês

10.1681/asn.v1291971

1533-3450

Thomas H. Hostetter,

Dialysis and Renal Disease Management

This is the Society's first meeting outside the United States. However, the organization was and still is chartered to accept membership from all of North America. Thus, we have numerous members from Canada as well as Mexico and Central America. My thanks go out to our host country. I am sure you will enjoy this lovely city. I would also like to thank those who have helped to make the organization run over the last year and who have helped to make my job easier. First, thanks to my fellow members of the Council who provided advice and hard work for our organization. Numerous members of committees of the Society have also worked diligently on many facets of the organization, only some of which will I have time to mention. To them, my thanks as well. The permanent staff of the Society stationed in Washington has had a trying year with a move of their offices and some turnover in staff. They remained cheerful and hardworking. We owe them a great deal. My colleagues at the University of Minnesota have shouldered responsibilities for me during this year, for that I am grateful. Patty Johnson has been my right hand in this job. She has been superb. Finally, family and friends have provided counsel and encouragement during this year. The meeting depends on corporate support. I want to acknowledge these most generous patrons. A special thanks goes to the Program Committee members who were responsible for most of what you will be enjoying over the next four days. This committee worked hard, as always, but with remarkably good humor. They showed judgment and taste in constructing your menu for this meeting. They are the Chair, Tim Meyer, Sharon Anderson, Joseph Bonventre, Michael Caplan, Ricardo Correa-Rotter, Allison Eddy, Jonathan Himmelfarb, Charles Jennette, Christopher Lu, Victor Schuster, and Stefan Somlo. There are some key changes in the staff of the Society at our Washington office. First, Julia Janko took over as our Executive Director in the Spring of this year. I am grateful for her committed, strenuous effort. As Bill Bennett announced at last year's meeting, Bob Narins was chosen for a new position, Director of Postgraduate Education. Bob is now charging ahead in that job. Craig Tisher's tenure as the Editor of the Journal of the American Society of Nephrology will be coming to a close next June. We are in the final phases of a search for his successor. However, I am quite sure that no one can replace Craig's determined advocacy for the Journal or his thorough-going concern for its quality. During his editorship, the Journal has prospered magnificently. It is one of the treasures of the Society. Craig and his editorial group deserve tremendous credit for maintaining and enhancing the quality of our Society's journal. Finally, Jill Rathbun, Director of Government Relations, will be going back to graduate school next fall. She has been tireless in her efforts, unfailingly cheerful, and highly effective. I thank her as well. The Society is extremely broad in its scope. Any report I give to you will necessarily overlook certain features of the previous year's accomplishments. Thus, I apologize at the outset to those who have worked in areas that I will not have time to discuss. In addition to our core emphases on providing a forum for scientific interchange and continuing education at this meeting and the dissemination of the information through the Journal, the Society sustains a government relations advocacy program. A number of important issues have been addressed through this program over the last year. First, in response to the National Institutes of Health's (NIH) decision to reorganize their review process, an integrated review group dealing with kidney and urologic diseases was included. One of the Council members, Bill Mitch, has been particularly active in this area and we are now at the forefront in submitting proposals for actual new study sections in the next phase of this process. Bill and the staff with the Government Relations group have done a tremendous job in getting us ahead in this effort. A consistent theme of the Renal Research Retreat, organized 2 years ago by Wadi Suki, was the need to harness the burgeoning harvest of genetic information and bring it to bear on kidney-expressed genes. In this regard, we have advocated for a kidney genome initiative within our institute at the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases. That initiative is moving ahead. Indeed, at this meeting. Robby Starr from the NIH staff will be holding a meeting to obtain thoughts on needs for genomic research and related bioinformatics. In the past, the Society has not reached out extensively to patient groups. We have rather viewed ourselves as a professional and scientific group. Our government relations have focused on research interests. Indeed, those are still the primary lobbying interests of the Society with practice issues shared and lead through our affiliation with the Renal Physicians Association. However, it is abundantly clear that advocacy for research is most effectively carried to Congress by those who are most affected by research, namely, patients with kidney disease. For this reason we have developed a mail campaign to establish a cadre of patients willing to support kidney research at appropriate times. For the remainder of my time I will be discussing two topics. The first is the National Kidney Disease Education Project, an effort championed not only by our society, but the affiliated societies of CAKS, especially the President of the National kidney Foundation, Joel Kopple. The final point, to which I will also return in my later remarks, is a proposed Loan Repayment Plan for physician investigators embarking on investigative careers. This proposal was spearheaded by Lance Dworkin and our Government Relations Committee. The rationale for the Kidney Education Program is simple and direct. We are in the midst of an unabating crescendo of renal disease (1). Indeed, these data from the U.S. Renal Data System of 2000 show that the incidence of kidney failure has been increasing at a rate of 6 to 8% over the last decade. (Figure 1). At this compounded rate of increase, the number of patients coming into renal failure has doubled. Furthermore, over 300,000 people live with renal failure now, and nearly 100,000 U.S. citizens will develop it this year. Indeed, in certain areas of the United States and within particular ethnic groups, the disease is, without hyperbole, epidemic. It is only within the last few years that we have obtained some idea of the size of the pool from which they derive. Data extrapolated from the 1990 National Health and Nutrition Examination Survey (NHANES) were published by Jones and colleagues not quite 2 years ago (2). The NHANES is a periodic survey of 18,000 people selected to be representative of the demography of the United States. A full 10.8 million, nearly 6% of the adult population of the United States, have a serum creatinine of greater than 1.5 mg/dl. Of course, the numbers decline with increasing cutoffs. However, it is a dauntingly large group who are at some point on the road to end-stage renal disease (ESRD). We don't know how many of these people will progress to ESRD or their distinguishing characteristics. Indeed, many may succumb to other vascular complications perhaps bound up with their reduction in kidney function before reaching kidney failure. However, it is from this population that the huge burden of ESRD derives. Probably, most of these people have no idea that their kidney function is depressed. Like hypertension, renal disease is largely a silent disease. However, the public awareness of hypertension has changed over the last several decades. Data gleaned from the last report of the Joint National Commissions on High BP point out that of the individuals with high BP only about 50% of them knew they had it in the 1976 to 1980 period, and successively smaller protions were under any treatment and adequate control for that treatment (3). Those disturbing percentages were markedly enhanced by the next phase of this examination from 1988 to 1991; by which time, nearly three quarters of people with hypertension knew they had the problem, most were on treatment, and 29% were receiving adequate treatment. Those who have followed this trend have been concerned that improvement in awareness, treatment, and control has not continued in the last survey. Nevertheless, the numbers are much better than at the start.Figure 1: . Prevalence and incidence of treated ESRD since 1984 and projected to 2010. From USRDS, 2000.What was responsible for improved awareness and treatment of hypertension? Probably several factors, but beginning in 1972 the Heart, Lung, and Blood Institute of the NIH began a high BP education project. One of our members, our Secretary-Treasures, John Stokes, was instrumental in launching that effort when he was at the NIH. The effort is ongoing, and much of the increase in awareness and treatment of hypertension can be attributed to the program. Furthermore, if one simply follows the incidence of stroke and coronary artery disease over the last 25 to 30 years, there are dramatic reductions (Figure 2). No one claims that the initiation of the High BP Education Project was the sole reason for this decline. Indeed, the decline began somewhat before, but it probably helped. But, undoubtedly you will not have failed to note that in stark contrast to the relentless increase in the incidence of kidney failure, both stroke and coronary artery disease are on the decline. As you all know, treatment attenuates the course of renal insufficiency. If properly instituted, it may even prevent kidney failure in some individuals. Overall, the rates of loss of kidney function measured as a decline in GFR per year as reported in a number of studies conducted in the late 1970s and into the 1980s was about 14 ml/min per yr. By contrast, the rate of decline has been cut by more than half in studies conducted during the 1990s. Most but not all of the patients studied had diabetes and proteinuria and were treated with angiotensin-converting enzyme inhibitors. However, the point, I hope, is clear that, at least in studied populations, we can do something quite substantial.Figure 2: . Change in age-adjusted death rates for cardiovascular disease (CVD), including stroke and heart disease (CHO), between 1950 and 1996. The vertical line marks the beginning of the National High Blood Pressure Education Program.How are we doing in practice? Bits of data are emerging. Three years ago, a group from Emory, led by Dr. William McClellan, reported on this issue (4). These investigators examined the discharge orders in patients in both community hospitals and tertiary care centers. They found that among people with serum creatinine levels of 1.5mg/dl or greater only about a quarter of those with hypertension and less than one third with diabetes mellitus were treated with angiotensin-converting enzyme inhibitors, a standard of therapy stipulated by many practice guidelines. Furthermore, of those with detectable overt proteinuria, only about one out of eight hypertensive patients and one out of three diabetic patients were on this form of therapy. We do not know how well their BP was controlled. Furthermore, one suspects that patients who have not even been admitted to a hospital but who would meet these criteria of elevated creatinine and/or proteinuria are treated at even lower rates than patients who have been hospitalized for some reason. Thus, these data suggest that we are considerably behind the current situation for primary hypertension in terms of treatment and likely control. We are now about at the point with treatment of progressive renal injury where hypertension was in the early 1970s. We have effective therapy. They are both silent diseases with potentially disastrous outcomes. Screening is simple. There are advantages for patients, physicians, and industry in extending therapy. Indeed, some industries have begun to heighten public awareness of renal disease on their own. The time has come to mount a vigorous effort to educate the public about kidney disease, particularly individuals at high risk and urge them to seek treatment. We should continue to provide education to physicians, including primary care doctors. We will need practice guidelines as the National Kidney Foundation, and we with the Renal Physicians Association are developing. Even performance measures may ultimately be required to increase the rate of treatment. Hopefully, we can then begin to change the rate of increase of kidney failure as has occurred with cardiovascular disease. I am aware that this is a multifactorial process. Broad issues of healthcare delivery, in many ways peculiar to the system or lack thereof, in the United States contribute to this process, but I do not believe that we can hide behind those undeniable system problems and avoid doing what we can. I have a personal interest to acknowledge. I will be assisting Dr. Briggs and her staff at the NIH to develop such an education program by taking a leave of absence from the University of Minnesota to work on this program over the next 2 years. I will be calling on many of you to help me. However, as firmly as I believe in the importance of bringing current therapies to the largest number of people at risk, we cannot view the problem as one simply due to public ignorance or to lack of guidelines or to insufficient performance standards. We need to know more at fundamental levels to improve therapies that, while better than 20 years ago, are still far from perfect. Renal failure still supervenes even in many well-managed patients today. We need to understand even more about how to optimally apply the imperfect antihypertensive and dietary therapies that we have today. We need to know at an epidemiologic level, what percentage of people with renal insufficiency progress? What happens to the rest? What are the markers of progression? Molecular markers? Genetic markers? And even clinical and demographic markers? What are the physiologic mechanisms whereby these genetic and molecular markers emanate from or lead into progression? Obviously, to answer these questions and many others that should rightfully attract our attention, we will need investigators. The continued influx of younger investigators is essential. Furthermore, many of these problems, and facets of all of them, will profit by efforts from physician-investigators in particular. Here, we have a problem. Now, I am aware that the topic of the vanishing physician-investigator has been a staple of these sorts of talks since, at least, the late 1970s when Dr. Wyngaarden published a New England Journal of Medicine piece based on a presidential address entitled "The Clinical Investigator as an endangered species" (5). Since that time, a number of other eminent figures have sounded this concern. The issue has been raised often enough that many of us have become almost inured to it. However, after reading a position paper by Dr. Leon Rosenberg in Science last year and more recently a review by Zemlo and colleagues in the FASEB Journal this summer, I became convinced that the problem is even more acute (6,7). From that FASEB Journal report, the data indicate that the number of MDs enrolled in NIH-funded postdoctoral training programs has decreased by nearly 30% over the last ten years from relatively stable numbers before that. A similar trend has been noted in the number of first-time MD applicants for NIH grants over the last five to six years. Even greater downward trends for MD participants on NIH study sections are reported in the FASEB Journal review. These trends are in accord with the falling fraction of investigators less than 45 years old such that the distinct minority of grant holders are less than 45 years of age. Of course, the overall biomedical research enterprise still flourishes. PhD and MD/PhD scientists have always contributed to this continued advance, and rightly so. However, it seems likely that a lower limit exists at which progress in biomedical research will be notably hampered by an insufficient number of physician-investigators. In addition, depletion of scientifically trained faculty in clinical departments can only dilute interest in such careers among students. Any such social trends have complex underpinnings. I will not enumerate the multiple proposed causes for these trends. Instead, I refer you to Dr. Rosenberg's editorial in Science and the FASEB Journal review for more detailed analyses. Furthermore, I will not simply bemoan this situation, but rather, I want to show you that the Society has been addressing this issue at several levels for the last few years. First, a workforce analysis was performed in conjunction with sister societies. Although it was based on the needs for clinical practice, an effect of this document has been to enhance interest in nephrology among medical trainees and at least entice them into considering this specialty. My own nonsystematic survey finds that almost all directors of nephrology fellowship programs describe a distinct uptick in the quality and number of applicants over the last several years. Of additional importance was the decision in 1996 during Bill Couser's presidency to invite to this meeting medical residents and, more recently, pediatric residents who are interested in nephrology but as yet uncommitted. To date, nearly 500 residents have been brought to the meeting under the support of Society funds. I want to especially welcome the residents here today who are participating in that program. Efforts targeted more directly at supporting investigation, and particularly younger investigators, began with the decision five years ago to supplement first awards of the NIH, the so-called R29s, when they were too meager. Also, we have provided bridging support for NIH applications just missing funding in the form of Career Enhancement Grants. We have developed awards targeted at young investigators, now called the Gottschalk awards, which supply $75,000 a year for 2 years to investigators working in nephrologic areas. In the last year, Norm Siegel, along with Amin Arnaout and Joe Bonventre, developed a program to support medical students to take a year off from courses to work in a research setting while receiving a stipend as well as providing support to the laboratory. Joyce Yu of Mt. Sinai School of Medicine and Roy Mathew of Long Island Jewish Medical Center received those awards. Finally, we have identified the large debt most MDs face when leaving their training as a substantial barrier to choosing a career in investigation. The average debt now approaches $90,000 for the young physician who is by this point 30 or more years of age. Sustaining this debt while protracting ones training in investigation versus moving into a generally more remunerative practice makes for a painful choice. We are all mindful that multiple factors enter into this decision, but debt seems to occupy the mind for many. As we advocated loan repayment with Congress, it became apparent that other groups, most notably the Federation of American Societies of Experimental Biology (FASEB), had come to very similar conclusions and were proposing nearly congruent legislation. Thus, last summer we formed a coalition with FASEB. Since then, multiple other partners have joined. The proposal would provide a net $75,000 of loan repayment. The recipients would be chosen by competitive review at the NIH. We've had quite remarkable bipartisan support for this proposal with the Congress. Through the efforts of Roland Blantz, a draft bill has been produced in the offices of Congressman Brian Bilbray from California. We have great hopes that this bill will be passed in the current Congress, but if it gets caught in the last minute rush to the election, we have every expectation that it will pass in the next year [The bill supported by ASN and FASEB was not passed in the last Congress. However, authorization for loan repayment for clinical investigators was passed and the NIH is in process of formulating this program.] Furthermore, I hope that the Society wil consider backstopping, with our own funds, qualified applicants from nephrology who might just miss in the NIH review process. The decline in physician-investigators is a problem, but the Society is acting vigorously to rectify it. However, in the same sense that the answers regarding the rapid growth of ESRD are not simply better systems and better management but the continued attack on basic questions. Attracting MDs into investigative careers must rest on more than simply debt relief. I suspect that a large component of this problem of diminishing MD interest in investigation stems from our sometimes tortured absorption in the strains of current practice. Such distraction creates a reciprocal loss of attention to the many, large still unresolved but beautiful questions in nephrology. Many of you are deeply involved in solving some of these problems. But, I believe, we have not, and I include myself in this accusation, conveyed convincingly to students, residents, and nephrology fellows how intriguing, how pretty, many of these questions are. Indeed, students all too often view the science of nephrology and medicine as largely established and simply waiting for better systemization. Even worse, the incursion of management forces into the lives of their would-be teachers has led us to lament these burdens rather than to raise the attention of students at all levels to the fascinating and abiding puzzles. I won't presume to direct the research investigation of the discipline by myself. For that, I refer you to a rather weighty document derived from deliberations of our Research Retreat of 2 years ago (8). It listed multiple areas of investigation as goals for the few years. But, I did recently impose upon a number of eminent investigators within the Society to get their more impromptu views on major unresolved research issues. Those I interviewed were remarkably forthcoming, and listed in Table 1 are a few of their suggestions. Many more other fascinating particular areas were proposed as well. Great expectations are attached to the genetic study of hypertension as well as the risk for renal disease. Progress in knowledge and techniques as well as advances in animal models and in simpler forms of hypertension fuel this optimism. Substantial NIH support has gone to developing a network for the study of immune tolerance. Experts in this area view this as a realizable goal. You will hear more about xenotransplantation on Monday at the Plenary Session. Bioengineered kidneys and stem-cell therapies are also under exploration. The reclassification of tumor pathology by gene expression is something that our plenary speaker this morning has been instrumental in initiating. Such an approach to reorganization of renal pathology is more distant, but with newer techniques, such as laser capture and expansion in our knowledge of gene expression, this too may become the way we understand kidney disease. Perhaps the most time-honored field within nephrology is the study of salt, water, potassium, and acid regulation. Enormous detail is currently available. However, the regulation of these inorganic solute balances may still contain mysteries. It is only within the last decade that an actual biosensor in the extracellular fluid, a calcium sensor, was discovered. Whether sensors for pH or potassium will be identified and linked to homeostasis is unknown. But, as one eminent investigator in this area mused on the subject, he noted that perhaps examination by gene expression of organs other than the kidney coupled with newer informatic organization might identify new regulators of salt, potassium, and acid homeostasis. Uremic toxins have been of interest to nephrologists for decades. However, it is still remarkable that nearly a million people are dialyzed worldwide, yet no nephrologist believes that the procedure works simply by removing ions, water, and urea. We have almost no idea what chemical causes uremic symptoms. Another fascinating, but almost totally unknown area, is the molecular signal to compensatory renal growth as renal mass is lost. Finally, many of those with whom I spoke identified the establishment of disease registries and treatment cooperatives as a need. Many remarked that oncology has made advances on relatively rare tumors by such efforts. These efforts have been sorely lacking in renal disease. I would hate to think that we have failed to develop these systems simply because we have the option of placing patients on dialysis or transplantation. Even if our current therapies are rather modest for some diseases, an organized approach is likely to increase our understanding of the diseases and thereby suggest more sophisticated approaches to their management. I list these topics to emphasize to the students, residents, and fellows here that there are innately intriguing as well as practically compelling questions still open. Hopefully, such lists also serve to remind all of us that the field remains fertile. If we are to attract the best physician investigators, we should focus on these sorts of large issues and try to blunt our preoccupation with managed care, documentation, etc., as intrusive as they are.Table 1: Sample of outstanding problems in nephrologyThis Annual Meeting was begun as a forum to discuss the most current and exciting basic and applied issues in nephrology, but we must reawaken what I perceive as some diminution in our enthusiasm for these questions and take the core themes of nephrology home to our trainees. I hope this request will be taken as something more than a treacly admonition to just "think positively," although there may be some value to self-conscious attempts to elevate our concerns. I have a concrete suggestion, though. Take home from this meeting to your students a question or two, basic and/or clinical. Tell the students, of whatever stripe, what's new, but also let them know that mysteries remain. If you don't see students, do the same for your practice partners or the primary care doctors who consult you. I have called attention in this talk to two areas that are in some tension by usual measures. On the one hand, the Society has joined in support for public advocacy and public education hoping to apply current, if incomplete, methods for slowing the enormous increase in kidney failure. On the other hand, I have called us to refocus our attentions in a very systematic and conscious way on basic and clinical problems in nephrology. Can we do both? Can we, on the one hand, seek public and social change and simultaneously inspire fundamental research on the other? I think we can and should. Over the next five to ten minutes, I want to close by supporting that profession of faith in our ability to do both. To do so, I want to look back. For reasons that will become apparent, the New England Journal of Medicine of October 12, 1967 provides a useful point of reference. (9) It was a remarkably nephrologic issue. The lead article highlighted a problem that persists. That paper by the group of David Hume, the surgeon involved with the first renal transplant, was one of the early definitions of what has come to be called chronic allograft nephropathy or chronic rejection. The accompanying editorial pointed out that then, in 1967, only about 65% of living related donor grafts were working at 1 year and that less than half of those from cadaver kidneys functioned for a year. Of course, the results of transplantation are dramatically better today. Earlier in this current year, this same journal reported a 94% 1-year survival for grafts from living donors and an 88% rate for cadaveric ones (10). All that said, we still understand very little of the mechanisms or treatment of chronic allograft injury, the very subject of this article. Indeed, this process is now the major limit to transplant longevity. The article on "Physiology for Physicians" was by Dr. Arthur Guyton who has been one of the most persistent advocates of the notion that arterial hypertension resides in a defect in the ability to excrete sodium. Within the last decade, the molecular definition of one of the rarer forms of hypertension, Liddle's Syndrome, has proven Guyton's principle. However, the molecular understanding of the vast body of essential hypertension is, as I said earlier, still a work very much in process. The genetics article that week dealt with autosomal monosomy in man but was far from molecular. It was more like histologic genetics. Indeed, the accompanying editorial described the situation as "Clinical chromosomology in 1967" and noted that it had then been less than 9 years since the first chromosomal abnormality had been detected in humans. Needless to say, the molecular genetic definition of disease has exploded since these observations. The Clinicopathologic Conference of the Massachusetts General Hospital (MGH) turned out to be a case of Goodpasture's syndrome. The diagnosis was made, and unapologetically so (do they ever apologize at the MGH?), without immune localization of basement membrane-directed antibody. Immunofluorescence microscopy, now standard, wasn't then. On a more somber note, a special article was submitted by an Australian correspondent and dealt with medical aid in South Vietnam during the relatively early phases of that war which escalated in the next five years. I review this edition of the New England Journal of Medicine not just because of its nephrologic interest or to trumpet our progress, but also because it came out the week of the very first meeting of the American Society of Nephrology, 33 years ago. That meeting took place in Los Angeles and attracted about 1000 attendees with 300 scientific abstracts. There were four plenary speakers at that meeting, the same number as there are for our meeting now. We are indebted to Dr. George Schreiner for his precis of the meeting published later in Nephron. Dr. Louis Welt's discussion of clinical nephrology spanned renal biopsies to uremic biochemistry. Dr. Frank Dixon reported that nephritis could be induced in monkeys with antibody eluted from the kidneys of patients with Goodpasture's such as the one in that week's New England Journal of Medicine. Dr. Robert Berliner reviewed micropuncture, the split-drop technique and anatomic determinants of absorption. Finally, Dr. Daniel Tosteson supplied an analysis of membrane transport. The presidential address at that meeting was delivered by Dr. Neil Bricker and was entitled "Dialysis, Toad Bladders and Social Conscience: the Search for Balance" (11). The first term, dialysis, refers to the lack of organized support for dialysis for patients with renal failure in 1967. Toad bladders served as an icon for the interest of many of the founding investigators of the Society in water transport using this favored model system. Dr. Bricker addressed an issue that was quite contentious. The debate centered around whether resources, both financial and workforce, should be deployed in providing dialysis in a systematic way across the United States or whether those resources were better husbanded to basic investigation. Most of you are aware that it was not until 1973 that the Federal Government began to provide money for dialysis care in the United States. He asked whether the profession could do both. Could it provide life-sustaining care on a broad scale and continue to pursue research? He concluded in the affirmative. I quote "... as long as chronic dialysis treatment remains an acceptable technique for treating patients with end-stage kidney disease and transplantation is capable of sustaining meaningful life for one or more years, every effort must be made to increase the availability of these procedures. But, second, we must not accept our present state of knowledge. Rather, we must intensify, not diminish our broad based, multi-categorical attack on renal diseases." This was an era that many regard as the golden age of biomedical research in the United States. But even then, there were, as you see, serious dilemmas for nephrology, to say nothing of the crescendoing foreign war, still-tenuous civil rights for many citizens, and a near absence of women in medical research. Can we do less today? Only if we choose to be distracted by the narrowest quotidian concerns, as annoying and insinuating as they are. Finally, I'll quote a fragment of an address by the all-but-canonized, Canadian physician, Sir William Osler (12). He delivered this address to the Canadian Medical Association in 1902. "Never has the outlook for the profession been brighter. Every-where the physician is better trained and better equipped than he was twenty-five years ago. Disease is understood more thoroughly, studied more carefully and treated more skillfully. The average sum of human suffering has been reduced in a way to make the angels rejoice. Diseases familiar to our fathers and grandfathers have disappeared, the death rate from others is falling to the vanishing point, and public health measures have lessened the sorrows and brightened the lives of millions." His orotund, Victorian rhetoric with its evocation of his own golden age offends our current sensibilities. However, putting aside the triumphalism, Osler's optimism, stagy as it may have been, perhaps even to the degree that it was self conscious, is still worthy of our admiration. Some similar, if more subdued, strain of public optimism, I suppose, informed the assertion in 1967 at the birth of the Society that nephrology could and should do both, could and should promote research and patient care. There are, of course, golden ages only through memory's haze, but the problems, both practical and investigative, and the resources to solve them, have never been greater than today. It may not be the best of times, but it is far from the worst. In the United States, we are at peace and mostly affluent. We enjoy a more merit-based society than ever. Our major source of research funding, the NIH, is in the midst of major increases. Most importantly, an epidemic of renal disease awaits both the application of our current, best methods and the solution of beautiful, biologic puzzles. We can still do both. Our greatest risk lies not in overreaching, but rather in doing neither by doing something less.