Barry M. Brenner, M.D., of Wellesley, MA, renowned kidney physiologist and clinical nephrologist, Director Emeritus of the Renal Division at Brigham and Women’s Hospital and Samuel A. Levine Distinguished Professor of Medicine at Harvard Medical School, died peacefully, surrounded by family, on August 6, 2024, at the age of 86. Barry was born in Brooklyn, New York on October 4, 1937, the second child to first generation American parents, Louis and Sarah (Lamm), whose predecessors were farm laborers and garment workers confined to Jewish ghettos in areas known today as Eastern Belarus. Barry’s grades were average at best until his senior year in High School, when he decided that he wanted to pursue a career in medicine. From then on, he adopted a deep work ethic including 15- hours a day, 6-7 days per week study schedules, which enabled him to be the first in his family to graduate from college, which he achieved at Long Island University in 1958 in less than 3 years, with a B.S. degree with honors. He was then on to the University of Pittsburgh School of Medicine, graduating first in his class with an M.D. degree in 1962.
Four years of residency in internal medicine followed at Bronx Municipal Hospital Center, Albert Einstein College of Medicine from 1962-1966. During his second year he got hold of the newly released 1st Edition of Strauss and Welt’s Diseases of the Kidney, which he devoured and was especially enthralled with the chapters on kidney physiology. He knew then that kidney research would be his lifelong lodestar. Barry completed his internal medicine training in 1966, his final year as Chief Resident. He was offered post-doctoral renal fellowships in Boston and New Haven, but instead chose NIH where he joined the renowned Laboratory of Kidney and Electrolyte Metabolism led by the famed kidney physiologist Robert W. Berliner. There he worked closely with Julia Troy, his technically brilliant assistant who would become his chief lab technician for the next 40 years. In the late 1960’s, they and collaborators disproved the two theories then believed to explain how kidneys normally regulate body fluid balance.
In 1969 Barry was recruited to the University of California, San Francisco to lead the Nephrology Division at the Fort Miley VA Hospital overlooking the Golden Gate Bridge in San Francisco, CA. During seven extremely productive years in San Francisco, Brenner’s laboratory defined the normal physiology of glomerular filtration. The kidney is the body organ that acts to filter the blood of waste products via concentrated urine. Prior to that time, there was limited understanding of how the blood was initially filtered by the sieve-like portion of the kidney, known as the glomerulus. Brenner and his team harnessed the power of novel investigative tools and animal models to define glomerular filtration in the healthy state. During this prolific scientific period, Barry rose to full Professor, and was actively recruited to join many other medical institutions. In May 1976, 5 months before his 39th birthday, he arrived at the Peter Bent Brigham Hospital as Director of the newly established Laboratory of Kidney and Electrolyte Physiology and as the Samuel A. Levine Professor of Medicine at Harvard Medical School. In 1979 he became Director of the Renal Division at The Brigham, a position he held until 2001, when he was appointed as Director Emeritus at the renamed Brigham and Women’s Hospital and as the Samuel A. Levine Distinguished Professor of Medicine at Harvard Medical School.
It was in Boston that Barry and colleagues were able to utilize their existing investigative tools and animal models to build upon the now defined normal physiology of glomerular function and explore the kidney response to injury and disease. Brenner and his team demonstrated that when the kidney was injured and there were fewer viable functional units (nephrons), there was an inexorable decline with further nephron loss. Once an injury or kidney disease was underway, patients usually faced a progressive loss of kidney function ultimately resulting in organ failure and the need for replacement dialysis or transplantation to sustain life. Importantly, however, in the early 1980s, Brenner’s group demonstrated in animal models of kidney disease, the feeding of a low protein diet attenuated further kidney decline. Just at that time, angiotensin converting enzyme (ACE) inhibitors were introduced, which Brenner saw as offering a promising kidney protective mechanism of action. In 1986, Brenner predicted that ACE inhibitors would likely be clinically beneficial in animal models of chronic kidney disease.
Subsequent studies confirmed Brenner’s hypothesis. As with dietary protein restriction, exposure of rats to ACE inhibitors following kidney injury largely prevented further functional kidney loss. Thus, the potential for a clinically effective drug to offer renal protection was suggested.
Clinical confirmation of the kidney protective effect of the first US Food and Drug Administration approved ACE inhibitor, Captopril, came from results of a randomized clinical trial of Type I diabetic patients by Lewis and coworkers in 1991. Soon thereafter, Brenner led a similar randomized clinical trial (RENAAL) and reported significant kidney and cardiovascular benefits in Type 2 diabetic patients, using the new angiotensin receptor blocker (ARB) Losartan. These drugs were quickly promoted in treatment guidelines and their use by physicians was widely adopted for diabetics and soon extended to patients with almost every form of progressive kidney disease worldwide. The “Brenner Hypothesis” was coined. The widely held belief that chronic kidney disease progresses inexorably to kidney failure was soon discarded and millions of patients have since been able to be maintained with clinically stable kidney disease.
In keeping with this thread, Brenner went on to recognize that individuals are not all born with an adequate number of nephrons. This circumstance is common among those of low birthweight, usually due to prematurity or suboptimal intrauterine growth as sometime seen even in full term infants. In 1988, Brenner and co-researchers hypothesized that low nephron endowment at birth increases the later-in-life risk of developing hypertension and kidney disease. Other than the Brenner group, the nephrology community in general paid little attention to this novel idea for its first twenty years. The past decade and presently, however, has seen an explosion of interest, ranging from new research into processes and regulation of nephron development in utero, to early and later-life clinical kidney outcomes in affected individuals, including those with low birthweight who eventually served as living kidney donors and the kidney transplant recipients who received sub-optimally endowed organs.
Over his long and productive career Dr. Brenner published more than 730 papers and reviews. He served as Editor or Co-Editor of 49 books, and Editor-in-Chief of Current Opinion in Nephrology and Hypertension from its founding in 1992 until his final days. He was founding Co-Editor with Dr. Floyd C. Rector of four editions of Brenner & Rector’s THE KIDNEY and then as sole Editor of the next four editions before turning all editorial responsibility to six younger associates now engaged in production of the 12th edition. Dr. Brenner was invited to serve as Visiting Professor at more than 250 institutions and delivered more than 150 Special Lectures including many Memorial Lectures honoring paragons of yore. He greatly enjoyed rendering service to the greater nephrology and academic community, as member of several Study Sections for NIH, 26 editorial boards, and innumerable academic committees for Harvard Medical School and Brigham and Women’s Hospital. He served as Councilor and President of the American Society of Nephrology and American Society of Hypertension, and Vice -President of the American Society for Clinical Investigation and International Society of Nephrology. Together as Co- Chairs, Dr. Brenner and Dr. John Dirks travelled the globe as leaders of ISN’s Committee on Global Advancement of Nephrology (COMGAN) which brought modern concepts of diagnosis and treatment to practitioners who were hungry for new knowledge throughout the world. This was one of Barry’s favorite and devoted responsibilities.
In recognition of his outstanding contributions, Dr. Brenner was elected to membership in many academic and professional societies including Alpha Omega Alpha; American Society for Clinical Investigation; Association of American Physicians; American Academy of Arts and Sciences; and Fellow of The American Association for Advancement of Science; New York Academy of Sciences and Royal College of Physicians of Great Britain. He was also elected to Honorary Memberships in many national societies of nephrology or hypertension including Greece, Czech Republic, India, Argentina, Cuba, South Africa, and Lebanon. Honorary doctorates were conferred from several universities including his alma maters Long Island University and University of Pittsburgh, University of Paris- Marie et Pierre Curie, Charles University, Prague, and Universidad Complutense, Madrid.
Barry has also been the recipient of many awards. He is the only individual to receive all three major awards from ASN since inception, namely 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) as well as establishment of an Endowed Annual Brenner Lecture. He also received the David M. Hume and Donald W. Seldin Awards of the National Kidney Foundation (USA); Jean Hamburger Award, A.N. Richards Award, Amgen Prize and Endowed Brenner-Dirks Lecture of the International Society of Nephrology; George E. Brown Memorial Award and Novartis International Award, Council for High Blood Pressure Research of the American Heart Association; MERIT Award, NIH, Richard Bright Award, American Society of Hypertension; Bright, Masugi, Volhard Medal, Japanese Society of Nephrology; Gordon Wilson Medal, American Clinical and Climatological Society; Gold Medal, Fundacion Conchita Rabago di Jimenez, Madrid, and finally and especially meaningful to Dr. Brenner, two Distinguished Alumnus Awards, one from the University of Pittsburgh School of Medicine and the other from the entire University.
Throughout his career Dr. Brenner enjoyed bedside teaching rounds with medical students, residents, and clinical fellows, employing wherever possible concepts taken from renal and cardiovascular physiology to explain observed physical and chemical manifestations of disease. He likewise enjoyed frequent review of data obtained by laboratory fellows, encouraging their interpretations of results, ideas about next experimental steps to be taken, and review of manuscripts in preparation. Regrettably, space limitations prevent identifying all of Barry’s many trainees and more senior collaborators whose contributions he made every effort to extol.
Dr. Brenner leaves a treasure chest of memories in the hundreds of family, friends and colleagues who knew him as a considerate, compassionate and thought-provoking but also somewhat acerbic personality. Despite formidable commitments he cherished time with Jane, his devoted wife of 64 years, their adult children Robert Brenner, M.D. and Jennifer Ash, Ph.D., Rob’s wife Molly and children Elliott and Abigail, and Jen’s husband Ron and children Samuel and Max. Indeed, nothing brought Barry more joy than spending time with his four grandchildren and engaging and encouraging them as they matured into young adulthood. Predeceased by his sister Arlene (Halper), he cared deeply for his cousins, nieces, nephews, and their extended families. To the end, Barry maintained strong ties via email with many friends and associates, sending and receiving often lengthy expositions on a wide range of topics including past reminiscences and rants addressing current political sanity and insanity, most often the latter. He enjoyed quoting from Churchill and adopted his habit of ending emails to cronies with the letters KBO, meaning “keep buggering on.”
This depiction of the highly accomplished life of Barry Brenner could hardly have been predicted, given the very modest background from which he came. Yet he long held that these seeming limitations were, in fact, empowering as they served to motivate a yeoman work ethic and an undistracted focus to every challenge he chose to meet. The result is more than a half-century of uncommon creativity, grand achievement and several theories that will, even from this early perspective, very likely endure. As illustrated by the life of Isaac Newton, theories if confirmed and accepted widely merge into Doctrines, Principles, and perhaps even Laws. In Brenner’s case they will most certainly provide motivation, opportunity, and direction for generations of young scientists who choose to follow and extend his ambitious pursuits. To him, instead of the familiar sentiment “Rest in Peace” we think he would prefer our sending him off saying, “Barry, Keep Buggering On!”
Reference: In Memoriam of Barry M. Brenner, MD: October 4, 1937-August 6, 2024. Robert M. Brenner, M.D., Barry M. Brenner, M.D. and Richard J. Glassock, M.D. Journal of the American Society of Nephrology. Published online September 9, 2024. JASN-2024-001092.
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