While surgery has traditionally been the only option for patients suffering from a rare condition known as retroperitoneal fibrosis (RPF), Johns Hopkins researchers have now developed a medical therapy to treat and cure this progressive disorder.
The condition begins with inflammation surrounding the infrarenal aorta. As the disease progresses, the inflammation leads to fibrosis, with compression of the aorta, vena cava and ureters—and if left untreated, kidney failure.
Until recently, physicians have relied on surgery to relieve the obstruction, using stents followed by open or laparoscopic ureterolysis to relocate the ureter. “But that approach doesn’t address systemic symptoms, such as pain, weight loss and anemia, or the disease’s underlying causes—inflammation and fibrosis,” notes Paul Scheel, director of the Division of Nephrology at Johns Hopkins.
Scheel has pioneered a new nonsurgical approach to RPF that combines two drugs—prednisone and mycophenolate mofetil (MMF)—that are administered daily until resolution of the retroperitoneal mass. In an initial study of 31 patients with RPF, all who received the drug therapy saw their systemic symptoms resolve, and nearly all of their obstructed ureters (30 of 32) were obstruction-free after the drug therapy ended, Scheel notes.
Buoyed by these results, he and his colleagues have now used the prednisone/MMF combination therapy to treat 234 patients with RPF at Johns Hopkins. Using the drug therapy, they’ve achieved a response rate of 95 percent and a recurrence rate of just 5 percent.
“The prednisone/MMF drug combination has sparked a paradigm shift in the treatment of RPF,” says Scheel. “The disorder, which was treated for many years with surgery alone, was associated with significant morbidity. It can now be treated medically, resulting in a complete resolution of disease in the vast majority of cases and with few side effects.”
As Scheel and his colleagues have emerged as world leaders in the clinical care of RPF—which typically develops in late middle age and is more common in men than women—they are now turning their attention to the disease’s root causes, about which little is known. Using blood collected from RPF patients, they are working with collaborators in Italy to uncover the genetic basis of the disorder.
They have also expanded their clinical practice to include other diseases of the retroperitoneum. For example, the Johns Hopkins Division of Nephrology is one of three national centers of excellence in managing patients with Erdheim-Chester disease, a rare non-Langerhans histiocytosis that can also lead to inflammation and fibrosis around the kidneys.