Neal S. Bricker (1927-2015).

Kidney International (2015) 88 425 Leon G. Fine1,2 1Cedars-Sinai Medical Center, Los Angeles, California, USA; and 2University of California, Los Angeles, California, USA Correspondence: Leon G. Fine, Cedars-Sinai Medical Center, Davis Building 5093, 8700 Beverly Boulevard, Los Angeles, California 90048, USA. E-mail: Leon.Fine@cshs.org I t is telling to reflect upon the fact that it is often not easy to identify the essence of the contributions of eminent academics and to capture this succinctly in one or two sentences. For Neal S. Bricker, who died on 4 May 2015, this is not the case. Quite simply, Bricker taught us that the failing, chronically diseased kidney behaves in an understandable and predictable way. And that is it. How could it be, he asked, that when three-quarters of renal function is lost, the composition of the body fluids remains reasonably normal? Either evolution has endowed us with far more kidney function than we need, or whatever remains viable in the diseased kidney must be subject to an adaptation, driven by definable biological processes, that allows for survival of the organism in the face of disease. It was this latter option that Bricker chose to study throughout his professional life. Neal Bricker phrased ideas in a way that made one remember them: the ‘intact nephron hypothesis,’ the ‘trade-off hypothesis,’ the ‘magnification phenomenon.’ All of these ideas were based on the basic understanding that, in the chronically diseased kidney, it is the surviving nephron population that is able to pick up the load of its lost fellows. Truth be told, this idea was first proposed by Robert Platt (1900–1978), from Manchester, UK, in two seminal papers published in the early 1950s. Had there been no additional studies published along these lines, it is entirely possible that these papers would have been passed over as being of some interest but of no specific import. Bricker, however, immediately appreciated the beauty and the importance of the concept and launched a lifelong research program that, over many years, showed that, regardless of the nature of the disease, or the nature of the solute under consideration, the chronically diseased kidney is able to maintain external balance far into the course of the disease. His research included studies in small animals, large animals, and humans, and bored down into mechanisms at the singlekidney, single-nephron, cellular, and membrane levels. In his engaging lectures, Neal Bricker was always inspiring. He used very few slides, and regardless of the topic, they always looked more or less the same. For instance, to illustrate his ‘intact nephron hypothesis,’ one slide would compare a normal-sized, smooth kidney on the left and a miserable, shriveled kidney on the right. Both, he showed, are able to regulate the excretion of a wide variety of ions and solutes with equal precision. Another slide would compare a normal nephron on the left and a proud, hypertrophied ‘intact nephron’ on the right. The latter represented a nephron from a diseased kidney, which had adapted to retain its ability to respond to the regulatory needs of the organ in an appropriate direction. He would insert the relevant transport processes—sodium, potassium, phosphate, and so on—into the illustration and explain, in the language of transport physiology, how the surviving nephrons have adapted to meet homeostatic demands in the face of a declining total renal mass. As the number of surviving nephrons decreased, the magnitude of the adaptation of each nephron would have to increase, which he referred to as the ‘magnification phenomenon.’ This led him to the notion, also previously suggested by Platt, that extrinsic forces (such as hormones) could trigger the adaptive processes associated with the evolving uremic state. The search was then on for hormones that could be involved: perhaps parathyroid hormone to regulate extracellular calcium concentrations and promote increased phosphate excretion per nephron, or perhaps a ‘natriuretic hormone’ to promote natriuresis or a ‘renotropin’ to promote nephron hypertrophy. In this context, it was the central importance of sodium homeostasis that captured his imagination, and his consequent search for a natriuretic factor dominated his efforts for decades. The notion that some of the effects of hormones could be salutary for some renal functions on the one hand, but adverse for the function of other organs, led to the ‘trade-off hypothesis.’ For a certain gain, there is a price to pay. Thus, using parathyroid hormone as an example, he viewed the increase in parathyroid hormone levels concomitant with declining filtration function as a mechanism of controlling calcium and phosphate excretion per surviving nephron. The downside of Neal S. Bricker (1927–2015)