A New Diagnostic for Kidney Disease

MED prof honored as BU Innovator of the Year

Suggest to David Salant that his research must have taken a long time and you’ll hear a dry chuckle.

“How about 30 years?” Salant says.

Salant, a School of Medicine professor of medicine and of pathology and laboratory medicine and chief of the nephrology section at Boston Medical Center, was named the University’s Innovator of the Year July 14, honored for his work identifying an antigen implicated in an autoimmune form of kidney disease called membranous nephropathy. The discovery has the potential to change the lives of hundreds of thousands of patients.

The award, presented each year by the Office of Technology Development, recognizes a BU faculty member whose cutting-edge research has been brought to market and benefits society at large. Salant’s discovery has been licensed to Germany-based Euroimmun, which quickly developed tests that were approved by the Food and Drug Administration (FDA) last year. Salant says the tests will provide quicker, easier diagnosis and also help measure the response to treatment of the kidney disease.

“Dr. Salant serves as a role model for students and other physicians looking to transform patient care by turning their own discoveries into practical applications,” said Gloria Waters, BU vice president and associate provost for research, as she presented the award to Salant at Technology Development’s sixth annual Tech, Drugs, and Rock n’ Roll event.

Salant first encountered membranous nephropathy, which occurs when the immune system goes awry and produces antibodies that attack healthy kidneys, in the early 1970s, when working in a teaching hospital in his native South Africa. “The first patient I encountered was a man in his early- to mid-40s with a young family, a good job. This was a devastating illness to him,” Salant says. “He got progressively worse and ended up on dialysis. I was fascinated by the fact that this was an autoimmune disease that no one knew anything about.”

The achievement—for which Salant shares credit with longtime colleague Laurence H. Beck, Jr., a MED assistant professor of medicine—was identifying the antigen, a protein called PLA2R, that is targeted by the immune response in 70 percent to 80 percent of the cases of the disease.

In 1977, Salant arrived at the Medical Campus on a research fellowship to work in a nephrology lab. Working with animals that had the disease, his group found antibodies to an unknown protein antigen in the glomerulus, the filtering unit of the kidney. But the equivalent in human cases was never established. It would take 30 years and one unintentional development for Salant, working with Beck, to identify a similar antigen in humans.

“Generally one adds a reducing agent to the protein mixture that one assumes contains the antigen, in order to open or unfold the proteins,” Salant says. “It turns out that if one does that, PLA2R is not identified by the circulating antibodies.” In other words, their method of looking for the connection had prevented it from happening.

“We left out the reducing agent for reasons that had nothing to do with what we were looking for and…then saw the protein,” he says. “It was somewhat serendipitous.”

David Salant receives Innovator of the Year Award

Vinit Nijhawan, Office of Technology Development managing director (left), and Salant (Photo to the right).

It took the researchers another year to firmly identify PLA2R, with the help of a collaborator in France and scientists at the University of Louisville using mass spectrometry. Their results, published in the New England Journal of Medicine in 2009, generated interest from investigators around the world and a number of companies, leading to the connection with Euroimmun.

“The number of human autoimmune diseases in which the target antigen has been identified can probably be counted on one or maybe two hands,” Salant says.

Although membranous nephropathy is classified as a rare disease, it affects hundreds of thousands of people around the world, according to Salant. After diabetes, it is the most common cause of the set of kidney malfunctions known as nephrotic syndrome, and one out of four patients develops end-stage kidney failure requiring dialysis or a transplant.

The current method for detecting membranous nephropathy is a kidney biopsy. Euroimmun tests for PLA2R with a blood test known as an immunoassay. The FDA does not currently recommend that it replace the biopsy, but it at least gives doctors a second, less invasive option in confirming a diagnosis.

PLA2R can also be instrumental in monitoring the response to treatment for membranous nephropathy, Salant says. The disease is treated aggressively with immunosuppressive and chemotherapeutic drugs, much like a cancer would be, “and it is not a benign treatment,” he says. But until now gauging the progress of treatment has been difficult.

“If you can follow along with the treatment using the antibody levels and then stop treatment when the antibody levels fall to zero, then you know that the patient is in remission,” he says.

Beck and some of their European colleagues have even more recently identified a second antigen that accounts for about 5 percent of cases, Salant says. So is he going to find the antigen(s) for the remaining cases? “If I live long enough,” he says.

Several hundred people, from students and faculty to tech executives and venture capitalists, crowded into the George Sherman Union’s Metcalf Hall for the sixth annual Tech, Drugs, and Rock n’ Roll networking event, which also honored the winners of the Technology Development MAPP mobile app development contest.

Author Joel Brown can be reached at jbnbpt@bu.edu.