Brenner’s Unforgettable Legacy: Transforming Medicine and Renal Science for Generations

The young Barry Brenner – the most brilliant student you can ever imagine – was fascinated by Oppenheimer and his insights in the field of theoretical physics, particularly black holes and quantum mechanics. This youthful interest ignited his decision to devote his life to science.Widely regarded as the parent of contemporary nephrology, Doctor Brenner had an amazing career, marked by rapid and remarkable achievements at every stage. He completed his degree in Biology with honors from Long Island University before advancing to the University of Pittsburgh School of Medicine, earning the esteemed George Heard Memorial Prize in Medicine. For Doctor Brenner, research was not merely about generating new knowledge; it was about ensuring these insights profoundly impacted patients’ lives and directly contributed to treating diseases – a goal he consistently achieved.Following medical school, he had his residency at the Bronx Municipal Hospital Center where he had become intrigued by the kidney. By the end of his 4-year residency, he decided for the NIH Laboratory of Kidney and Electrolyte Metabolism, known for its ground-breaking work in renal physiology under Robert Berliner. His 3 years at the NIH revolutionized nephrology, disproving previous dogma on regulation of fluid reabsorption by renal proximal tubule and sodium handling suggesting instead the crucial role of hydrostatic and oncotic pressure in peritubular capillaries and in the control of glomerular filtration. As a follow-up of his studies at NIH, Brenner established a new laboratory at the Fort Miley VA Hospital in San Francisco, affiliated with the University of California School of Medicine. During his time there, he held several key positions, including Assistant Professor (1969-1972), Associate Professor of Medicine and Physiology (1972-1975), Senior Staff Member at the Cardiovascular Research Institute (1974-1976), and Professor of Medicine and Physiology (1975-1976).His pioneering research on the mechanisms of glomerular filtration during his 7 years in San Francisco had an enormous impact on the current and future advancement of knowledge in Nephrology and Medicine at large. He became highly sought after by the world’s most prestigious universities and chose to lead the Kidney and Electrolyte Physiology Laboratory of the Harvard Medical School, Brigham and Women’s Hospital.It was in Boston that Brenner expanding his research, discovered that the loss of a critical number of functional nephrons triggers a progressive decline in kidney function, ultimately leading to organ failure. In addition, as Director of the Renal Division at Brigham and Women’s Hospital, he also turned the Renal Division into the nation’s leading nephrology program, with multiple recommendations from US News and World Report.An important aspect of Brenner’s work was his exciting and controversial relationship with International Society of Nephrology (ISN) activities. In 1991, the Commission for the Global Advancement of Nephrology (COMGAN) was established. Leaders of ISN at that time realized that for ISN to be genuinely international, it needed to address the problems of the poorest, the most vulnerable patients without access to medications. Brenner was appointed as chairman of this initiative, a role that he accepted enthusiastically in partnership with John Dirks. Barry began his work in Russia, he encountered young people, and realized the need for educational programs, skills and infrastructures soon to be expanded to other countries. Under his leadership, COMGAN was tremendously successful. Several programs were launched, aimed at developing partnerships between high- and low-income countries to conduct clinical research, and for this purpose, Brenner visited several countries, spending the necessary time in each to speak with doctors and trainees to really understand what was working and what was not, to offer advice, to generously share his charisma, and to inspire enthusiasm in everyone he met. After more than 20 years of dedication to COMGAN, the relations between Brenner and the ISN have cooled, but at the end of the ISN meeting in South Africa, his last suggestion was illuminating. He reasoned that a future initiative of COMGAN (he never understood why they moved from COMGAN to GO) could focus on the issue of nephron number and development of kidney disease later in life, a subject that has attracted his interest since several years. The idea was that, particularly in emerging countries, women with high-risk pregnancies – such as diet with not enough proteins, hypertension and pre-eclampsia – should be identified and followed up in the long term. It could have been indeed an exciting project for ISN, but unfortunately, it was never taken into consideration. However, Barry’s suggestion resulted in two important papers: a consensus document in The Lancet and a review in Nature Reviews Nephrology. Around the same time, a meeting on the idea that early stages of life could have a relevant impact on adult health resulted in an entire issue of Nephron dedicated to the subject. These initiatives have been instrumental to expose the entire renal community to Barry’s visionary idea that renal, cardiovascular diseases and diabetes risk starts in utero.The numbers behind his prolific research career are truly remarkable: he authored hundreds of papers and reviews, published as Editor or Co-editor almost 50 books. Most notably, he founded the Brenner and Rector’s “The Kidney,” the world’s foremost textbook of Nephrology, co-editing the first four editions and later serving as sole Editor for the next four, before passing all editorial responsibilities to six younger colleagues.Beyond his publications, he has held 26 editorial board appointments, has participated in more than 250 Visiting Professorships and delivered more than 150 Special lectures, underscoring his profound impact on the field. In addition, he also served as member of numerous societies, including roles as Councilor and Vice-President of the American Society for Clinical Investigation, Councilor and President of the American Society of Nephrology and the American Society of Hypertension, Councilor of the International Society of Nephrology, Councilor and Co-Chairman of the COMGAN of the International Society of Nephrology, Councilor of the American Association of Physicians, and Chair of the Section on Medical Sciences of the American Association for the Advancement of Science, Councilor of the Association of American Physicians.His remarkable contributions to science, clinical practice, and academia have earned him countless awards, far too many to list individually. He is the only individual to have received three awards from the American Society of Nephrology: the Homer W. Smith Award (for basic science), John P. Peters Award (for clinical science), and the Robert G. Narins Award (for education and teaching) along with the establishment of an Endowed Annual Brenner Lecture in his honor. Among the other prestigious prizes he has received are: Fellow, Royal College of Physicians, London (1998), Jean Hamburger (1999), Amgen (2003), A N Richards (2015), and Life Time Achievement (2016) Awards, International Society of Nephrology, Novartis International Prize for High Blood Pressure Research, American Heart Association (2005). He has received honorary degrees from Harvard University (A.M., 1977), Long Island University (D.Sc., 1987), the Université de Paris, Pierre et Marie Curie (D. Med. Sci.,1992), Diploma, Charles University, Prague (1995), and Universidad Complutense, Madrid (2002).As for one of us (GR), at the beginning of our acquaintance, things were not always easy with Barry and in a couple of occasions I was truly upset. Over the time, we cultivated our relationship, both professionally and personally, which evolved to the point those years later, after his most recent visit, I received this unforgettable letter: “My usual dismal mood on arriving home from a long journey is typically due to weariness and frustration with airports. Yet despite a 3-h delay on top of the expected 14-h trip from Italy to house due to an unexpected late winter snow storm, Jane was pleasantly shocked to find me smiling and very relaxed on arrival at the front door. Why, she asked, was I in such unusual good humor? I told her that my 3 days in Bergamo were exceptionally grand in every respect. (…) Beppe, all this of course reflects our immense friendship and mutual admiration, based on years of sharing ideas and together moving our discipline to new levels of progress and respect.”Throughout the years, we had dinner together on several occasions. Barry always chose places with a unique atmosphere, where he sometimes brought his dear friends, among them Don Seldin, for whom he had great admiration, and Richard Glassock, the person who was closest to him even in his difficult times. Whenever he visited, I did my best to live up to his expectations. Once I took him to a special restaurant, “Lio Pellegrini,” and he was enchanted by it, both for the ambiance and the outstanding quality of the food.The very day after, on the occasion of a meeting held in Verona, speakers were treated at the finest restaurant in the city. Barry and I were seated far apart, he was at the most prestigious table in the company of the foreign guests, while I was seated at a minor table with young colleagues. The general atmosphere was that of a pleasant evening; everyone was happy with the location and the food. At a certain point, Barry wrote a note on a small piece of paper, handed it to the waiter with a nod in my direction. The waiter brought it to me to the curious and somewhat astonished glances of the other guests. I never told anyone what was written on that note; it said: “Lio Pellegrini was better.” This was so Barry: he would never pass up a chance for a quip. Moreover, his gesture toward me – I was only 30 at the time – in front of everyone made me, for the first time, feel like someone.Doctor Brenner was always generous with advice, which was never “maybe, I don’t know, it depends,” but rather a straightforward “yes” or “no.” And his advice was almost always the right one. One day, I found myself in great embarrassment after a phone call from Jerry Kassirer inviting me to join the International Editorial Board of The New England Journal of Medicine. He told me that it would be something prestigious for Italy and that I would be the first nephrologist on the Board, but he immediately added that this role was absolutely incompatible with any other editorial commitments. At the time, I was an Associate Editor of JASN and did not have the courage to tell Craig Tisher that if I accepted The New England’s offer, I would have to relinquish a position he had generously offered me. At one point, I considered turning down Kassirer’s offer due to my conflicting feelings. I was ready to decline, but before doing so, I asked Barry for advice. His response was: “As for the Nobel Prize you never know, but this is now. It is something you can’t refuse.” Again, a quip – this time about the Nobel Prize – but it was a priceless piece of advice, and it was the right one.