In Remembrance of Dr. Jared James Grantham, JASN’s Founding Editor-in-Chief

Jared James Grantham, the founding Editor-in-Chief of the Journal of the American Society of Nephrology (JASN), passed away peacefully on January 22, 2017 surrounded by his family and their love, and eulogized by an outpouring of remembrances and tributes as his passing became known.

Born (1936), raised, and educated in Kansas, and with a professional career essentially centered at the University of Kansas School of Medicine, Jared and his achievements were recognized and spotlighted on a national as well as an international stage. From the American Society of Nephrology (ASN), Jared received the President’s Medal Award, the Homer W. Smith Award, and the John P. Peters Award, and from the National Kidney Foundation, he received the David M. Hume Award. The International Society of Nephrology (ISN) bestowed on him the Jean Hamburger Award, and in conjunction with the Polycystic Kidney Disease Foundation, the ISN also awarded Jared the Lillian Jean Kaplan Prize for Advancement in the Understanding of Polycystic Kidney Disease (PKD).¹

Jared was actively involved in the ASN throughout his career, and in 1989, when serving as the Secretary-Treasurer of the ASN, Jared was invited by the ASN Council to lead its new journal, JASN. Assembling a team that consisted of a Deputy Editor, six Associate Editors, and a Managing Editor, Jared led and sustained the journal during those early precarious days when submissions to JASN were scant and survival of the journal was far less than secure.² Innovative ways were needed to provide JASN’s content, and in this regard, Jared’s resourcefulness included publishing the program and abstracts from the Annual Meeting of the ASN and soliciting reviews based on invited lectures delivered at this meeting. Under Jared’s leadership as its founding Editor-in-Chief, JASN eventually found a sure step and voice, garnered an ever-widening community of submitting authors, and gained the unwavering allegiance of an expanding readership—his leadership provided the indispensable foundation on which the current stature of JASN resides. When, after 6 years at the helm, he and his team handed over the leadership of JASN to C. Craig Tisher as the incoming Editor-in-Chief, Dr. Tisher praised their performance by noting that “Their combined efforts are to be applauded, for without the wisdom, devotion, and resourcefulness they demonstrated, the Journal would have remained only a dream.”³

Turning dreams into realities was something Jared did throughout his life. This is best illustrated by promises he made to two childhood friends Ronnie Wilkerson and Donnie Richard.⁴ While in grade school, Ronnie told Jared that he and his family suffered from PKD, a disease that would cause Ronnie noticeable gross hematuria, especially after football practice in later years, and a disease that would prematurely end his life; Jared promised that he would find a treatment for this disease.⁴ Donnie Richard was afflicted by polio, as was Jared in 1950, and both were admitted to the same hospital at the same time. Jared eventually recovered but was left with residual limb weakness, especially involving the right shoulder, and the subsequent need for cervical fusion (C2–C6) because of cervical kyphosis. Donnie, unfortunately, developed respiratory failure, a complication that, despite respiratory support from the “iron lung,” was one that proved fatal.⁴ During this hospitalization, as the outlook for Donnie dimmed, Jared made a pledge that he would do his “…best to live for both of us.”⁴ Jared delivered on both promises.

The path that would lead to a novel treatment for PKD began in research that Jared was introduced to in his first year of medical school by Paul Schloerb, a surgeon at the University of Kansas who was interested in the treatment of renal failure. Jared’s first publication assessed the removal of magnesium by dialysis membranes, and his continuing projects in this laboratory during medical school involved fluid and electrolyte disturbances. This led, after his residency, to a research fellowship at the National Heart Institute in the Laboratory of Kidney and Electrolyte Metabolism under the sponsorship of Jack Orloff, Maurice Burg, and Robert Berliner. This was followed by an appointment as a staff investigator in the same institute and laboratory. While under the mentorship of Maurice Burg, Jared innovated and refined the techniques used to study isolated perfused tubules, and thus the utility of this investigative approach in evaluating specific nephron segments. Jared focused on the collecting duct, and his seminal studies in this laboratory showed increased permeability in response to vasopressin and cAMP, the inhibitory effect of prostaglandins on these processes, and the secretion of potassium in this segment as sodium was reabsorbed. One cannot help noting that performing studies of isolated perfused tubules requires lapidary attentiveness and dexterity. That Jared became a pioneer in this technique is all the more remarkable given the physical limitations resulting from his prior illness with polio. Fortitude and resolve were among Jared’s many virtues, and these were evinced throughout his life and career.

Jared was recruited back to the University of Kansas School of Medicine as a junior faculty member in 1969, where he continued the study of isolated tubules. His first paper after his return was his single-author study in Science that showed increased deformability of the collecting duct by vasopressin as the latter promoted water movement.⁵ However, much more consequential with regards to PKD was his unexpected observation that isolated proximal tubules can secrete water when exposed to organic compounds, such as para-aminohippurate; the prevailing view at the time was that renal tubules exclusively reabsorbed, not secreted, water. This serendipitous finding concerning tubular secretion, along with the observation that the chemical makeup of fluid in cysts in a patient with PKD reflected tubular function,⁶ gave Jared his epiphany regarding the importance of tubular behavior in determining cyst formation and growth in PKD. In a series of brilliant observations, he and his colleagues showed that cystogenesis in PKD involved proliferative responses in the tubular epithelium coupled with tubular secretion of solute and water, and that both processes were driven by vasopressin and cAMP.^7,8 This led to the realization that these processes were potentially interruptible by vasopressin receptor antagonists, thereby affording a novel therapy for PKD.

The success of his scientific work was paralleled by ascending leadership positions at the University of Kansas Medical Center (KUMC). In 1970, Jared was appointed Director of the Division of Nephrology at KUMC, an appointment that brought out his remarkable leadership qualities, his capacity to discern and recruit talent to KUMC, and his ability to build an outstanding division. He recognized the importance of philanthropy in securing research support for PKD, and in 1982, he partnered with Joseph Bruening, a Kansas City businessman, to set up the Polycystic Kidney Research Foundation (PKRF), which became a major catalyst and sustenance for PKD research; members of the initial Scientific Advisory Board of the PKRF formed a core cadre of investigators who submitted and were awarded the first multi-institutional National Institutes of Health Program Project Grant centered on PKD. In 2000, Jared was named the Director of the nascent Kidney Institute at KUMC.

All along, his effort to secure a therapy for PKD based on the antagonism of vasopressin vigorously continued. Jared recognized the need for a valid biomarker to assess functional decline early in the course of PKD, and thus organized the National Institute of Diabetes and Digestive and Kidney Diseases–funded PKD observational study, Consortium for Radiologic Imaging Studies of PKD (CRISP); this study, published in 2006, showed that magnetic resonance imaging–measured kidney volume provided such a biomarker.⁹ Using this index as the primary outcome, along with changes in serum creatinine, the landmark paper by Torres et al.¹⁰ in 2012 showed that the V₂ receptor antagonist, tolvaptan, retarded the progression of PKD. In reflecting on what was needed to advance to this point after the inception of the PKRF in 1982, Jared observed that “History will show that it took several hundred scientists 30 years and hundreds of millions of dollars of private and federal loot before the first treatment specifically targeting PKD was announced in 2012.”⁴

In addition to his devotion to his family and nephrology, Jared had diverse interests and talents, including performing vocal solos, singing in the church choir, and writing children’s books and poetry. He had a superb command of the English language as is so evident in his autobiography, which is filled with many eloquent and moving passages, such as:

“Some ecstatic images will remain imbedded in my memory for the rest of my life—my gorgeous future bride as she sat directly across the chancel from me in the Baker University choir; the adorable little faces of our newborn children; and, the first time I saw a freshly-dissected, perfused, living collecting duct magnified 200 times—all love at first sight!”⁴

Steve Jobs famously said: “You can’t connect the dots looking forward; you can only connect them looking backwards. So you have to trust that the dots will somehow connect in your future.” Jared firmly trusted in and committed to his career’s direction and focus; connecting the nodes that form the network of his accomplishments is thus relatively easy. Jared was always driven by his prevailing sense of purpose in life, one broadly directed to helping others and those, in particular, afflicted by PKD; by his adamantine determination to overcome personal challenges and reversals; by his steadfast belief in communal effort in enabling progress; and by his inimitable capacity to see joyousness in life’s seemingly small moments. Jared will forever be remembered for how much he touched and improved the lives of patients with kidney disease, especially those with PKD, and how much he made the discipline of nephrology an inestimably better one for us all.

Disclosures

None.