Robert Schrier, MD
Dr. Robert Schrier was at UCSF from 1969-72 as an Assistant and then Associate Professor. He left to become Head of the Division of Renal Diseases and Hypertension at the University of Colorado (1972-92). He has been considered one of the most successful Chairs of Internal Medicine in the country (University of Colorado 1976-2002). He is the editor of the textbook Diseases of the Kidney and Urinary Tract, now in its 8th edition. Dr. Schrier has served as President of the American Society of Nephrology (1982-83), National Kidney Foundation (1984-86) and International Society of Nephrology (1995-97).
On his research while at UCSF: Well, at that stage, someone told me that everything was known about water homeostasis and that I shouldn't study that. But we became interested in catecholamines because there had been some in vitro data suggesting that alpha-beta adrenergic stimulation had an impact on water transport in the nephron. And so we wanted to see whether or not that was an in vivo phenomena. It was pretty important because the bioassay then for anti-diuretic hormone could not distinguish between hyponatremic and normonatremic patients. So there was a suggestion either there's a reset osmostat (different sensitivity to the hypothalamic osmo receptors) or it's a primary intrarenal regulation in the circumstances where the degree of hyponatremia and hypoosmolality should have shut off ADH, leading to free water excretion and avoided hyponatremia. But there was clear evidence that advanced heart failure and advanced liver disease were associated frequently with a degree of hypoosmolality that would have turned off ADH. And since the bioassay was not sensitive enough, what we did in the in vivo studies was to use hypophysectomized animals that were glucocorticoid replaced. It was really relatively simple to go through the buccal area and take out the pituitary. And to our surprise, those effects - the antidiuretic effect of alphaadrenergic stimulation, first of all, was independent of osmolality, and was 100 percent dependent on the presence of ADH. So what was being seen in vitro, and was thought to be ADH-independent, in vivo it clearly was ADH dependent. So we thought that we were on to something, and the question was, was this a different pathway than the osmotic regulation of ADH. And we did arterial baroreceptor denervation in a series of studies, and showed that the effect of those non-osmotic effects on ADH with alpha and beta adrenergic stimulation were totally abolished. I think that sort of opened up the era of the nonosmotic baroreceptor pathway and that it's less sensitive that the osmotic regulation of vasopressin which is regulated 1 to 2 percent change in osmolality, whereas the change in blood pressure or blood volume needed about a 8 to 10 percent change. But when it occurred, when that non osmotic baroreceptor pathway was stimulated, the levels were much higher for vasopressin. And that suggested that not only the V2 but also the V1 vascular effect of vasopressin might be important in patients with heart failure and cirrhosis. And that led us to the hypothesis which we studied for a long period of time about body fluid volume regulation, and suggested that non osmotic baroreceptor-mediated vasopressin was the pathway for hyponatremia and heart failure and cirrhosis. What this needed first of all was a sensitive RAI bioassay, and once I moved to Colorado we developed that. And that clearly showed that at levels of osmolality that would suppress vasopressin, that didn't occur in patients that were hyponatremic with heart failure or cirrhosis.
On trainees and colleagues at UCSF: Tom Berl13 had finished one year of his fellowship and he finished the second year with me in Colorado, and then he came on the faculty. And John Conger had finished his fellowship in San Francisco and he came with me also when I came to Colorado. I have a huge respect for San Francisco, and a lot of loyalty. Holly Smith and I continue to have good contact, and I saw Larry Earley 2 recently. That's when we were in Philadelphia we saw Larry. And Barry and I have a good relationship. In fact, I gave the first Barry Brenner lecture at the Brigham two or three years ago. So I think I'm proud to have been associated with Larry Earley and Barry Brenner, and Holly Smith, and I owe San Francisco a lot because the training that Tom Berl had and John Conger received, helped us launch our Division in Colorado.
13. Dr. Tomas Berl went on to become Chief of the Division of Renal Disease and Hypertension at University of Colorado and was President of the ASN from 2004-05