November 09, 2011
By C.J. Janovy
|Jared Grantham, MD|
When Jared Grantham, MD, accepts the John P. Peters Award from the American Society of Nephrology this week in Philadelphia, reinforcing his stature as one of the world's foremost scientists in the field of kidney disease, he will likely think back to his childhood friend in Johnson, Kan.
"Ronnie Wilkerson and I used to trade comic books on the kitchen floor under our mothers' skirts," Grantham says. "One day he was kind of sad. He said, 'I have cysts in my belly. My mother has them, and my grandmother had them.'"
As a sixth-grader, Grantham didn't know what to make of this revelation. But he was reminded of it when he and Ronnie played together on the football team in high school. "We were relieving ourselves at the latrine, and I saw blood coming from Ronnie. He told me not to worry — it was just because one of the cysts had ruptured. Blood in the urine gets your attention."
Grantham remembered their childhood conversation. "He had used the past tense to describe his grandmother. He had been to her funeral just before that day. He knew early in his life that he would have kidney problems. At that point, there was no way to treat them."
Wilkerson would go on home dialysis and have three unsuccessful attempts at kidney transplants before he died. "Someone today," Grantham says, "we'd be able to help."
That's largely because of Grantham's work.
Grantham went on to major in biology at Baker University and finish medical school and his residency at the University of Kansas School of Medicine. Then he went to the National Institutes of Health for a research fellowship in the Laboratory of Kidney and Electrolyte Metabolism with Maurice Burg, MD.
In those days, the kidney — a fist-size organ made of a million tubes, called tubules, each about the size of a human hair, processing 50 gallons of plasma to produce 11/2 quarts of urine every day — was still a mystery.
Working with Burg at the NIH, Grantham says, "We took the kidney apart, went in and dissected each tubule to study in vitro." Plasma enters a filter at the beginning of each tubule; as the fluid moves along, tiny pumps and leaks allow essential substances to re-enter the blood. "I manufactured a miniature glass micropipette," Grantham says, "and stuck it into the lumen, pushed fluid into the tubule, collected it on the other end and did chemical tests to determine what a particular tubule was doing."
Grantham discovered that each tubule had different parts that modified the fluid pushed into it. "First it pumps out glucose, and amino acids, then sodium chloride — ordinary table salt — and water."
In 1969, Grantham was recruited back home to KUMC, where serious attention to the study of renal tubular function had begun under the direction of Lawrence Sullivan, PhD, in 1965. In 1970, Grantham was named director of the Division of Nephrology. Sullivan and Grantham would go on to found the Journal of the American Society of Nephrology in 1989 (by the time their editorial terms ended in 1996, the journal had the highest impact factor among more than 30 titles in nephrology and urology throughout the world — and still does).
During an experiment near the beginning of his time back at KUMC, Grantham found that what should have been an inert chemical normally found in urine caused the tubule to secrete fluid, bringing water back into the tube instead of absorbing it. No one had seen this secretion mechanism, and Grantham might have been tempted to dismiss it as an artifact — but he remembered his old friend.
"Ronnie Wilkerson popped into my head because sacs of fluid were developing in the kidneys," he says. Knowing he was on the right path, Grantham went on to study patients with polycystic kidney disease (PKD), determining the cysts were actually swollen renal tubules secreting fluid into expanding cavities.
Working in a rich research environment marked by collaboration among basic scientists and physician scientists — in one award acceptance speech, he described them as "a priceless community of laboratory colleagues" — Grantham ultimately mapped the life cycle of the renal cyst. And by the early 1980s, he had caught the attention of Joseph Bruening, a Kansas City real estate developer whose wife was on dialysis with PKD and whose daughter also had the disease. Bruening was concerned about his grandchildren and wanted to talk about how to encourage more research. He and Grantham started the Polycystic Kidney Disease Research Foundation, which now funds more than $2 million in national and international grants and has influenced federal support for PKD research to the extent of an additional $30 million per year.
For that work, Grantham was honored in 2003 with the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease. For using the technology he helped develop at the NIH to understand what was happening in the tubules, he had already been recognized by the American Society of Nephrology with the 1992 Homer Smith Award, the association's highest honor, given to individuals who have made outstanding contributions that fundamentally affect the science of nephrology.
This week in Philadelphia, Grantham will accept the American Society of Nephrology's John P. Peters Award, given to individuals "who have made substantial research contributions to the discipline of nephrology and have sustained achievements in one or more domains of academic medicine including clinical care, education and leadership."
Grantham will join just two others who have won the both the Homer Smith award, for basic science, and the John Peters award, for clinical science: Barry Brenner, MD, of Harvard, and Gerhard H. Giebisch, MD, of Yale.
That a KUMC scientist is among such esteemed company will not be surprising to anyone who has followed Grantham's career.
However, PKD remains one of the most common of all life-threatening genetic diseases, affecting 600,000 Americans and 12.5 million people worldwide. It is more common that cystic fibrosis, muscular dystrophy, hemophilia, Down's syndrome and sickle cell anemia. There is still no known cure.
Which is why Ronnie Wilkerson will still be on Grantham's mind when he returns from Philadelphia. Here, KUMC's Kidney Institute, which Grantham founded in 2000 and is now directed by Alan Yu, MD, counts 28 faculty investigators — 14 clinicians and 11 basic scientists — and more than 50 research associates, graduate students, fellows and support staff. They know that their work is not done.