Brian Kaplan was a 14-year-old high school freshman when he was diagnosed with lupus kidney disease. His aunt had died from lupus years before, so the diagnosis felt decidedly grave.
Kaplan was prescribed a course of cyclophosphamide, a chemotherapy drug developed for treating various types of cancer that is used off-label to try to halt the progress of lupus. And with the treatment came another piece of grim news: He might never become a father, because cyclophosphamide is known to cause infertility in both men and women.
“At that point, my dad even suggested going to a bank and freezing” sperm, says Kaplan. “I didn’t want to do it, but it was always something in the back of my mind. But then, I was also worried about not even living long enough to be a father.”
Twenty-six years later, the Washington, DC, resident is not only surviving, but also chasing around a gleeful 3-year-old son. The cyclophosphamide didn’t cause infertility, and after a few major flares of the disease—most notably in college, when his kidneys nearly failed—doctors have told him the disease is active, but low-grade and not progressing. “I wish it were a full-on remission,” he says, “but this is a close second.”
Los Angeles resident Dawn Snow also experienced her first symptoms of kidney disease due to lupus at a young age—in her 20s.
But in two big ways, Kaplan, now 40, and Snow, now 33, have had vastly different experiences. For one, Kaplan had the advantage of a mother who recognized his aches and red face as lupus and wouldn’t give up until she persuaded his doctors to perform a kidney biopsy. The biopsy showed kidney involvement. Within 10 days of showing symptoms, he received his first dose of cyclophosphamide.
Snow, meanwhile, wrote off first her hair loss, then her fatigue, and later her aching joints as “superwoman syndrome” from caring for her mother, fostering her newborn nephew, and working two jobs. She wasn’t diagnosed until her markers for the disease were triple what her mother’s were when she was diagnosed with lupus four years before.
And second, Kaplan’s family had health insurance and access to National Institutes of Health (NIH) doctors to treat his lupus kidney disease, while Snow had no insurance at all. Even after she was diagnosed, Snow didn’t get a second opinion when a doctor told her not to worry about her kidneys. As a consequence, Kaplan is healthy enough to work at a full-time job for the Department of Homeland Security, and Snow receives Social Security disability insurance payments and must endure dialysis treatments to remove toxins from her blood three times a week.
Kaplan is lucky his disease was caught as early as it was, since early diagnosis meant his kidneys were not as damaged as they might have been. Still, in the 1990s, doctors had few medications—cyclophosphamide, azathioprine, and corticosteroids—to treat lupus kidney disease. Today, though Snow’s kidneys have suffered more damage, her doctors have more treatment options to choose from, as well as the benefit of several landmark studies and improved treatment guidelines. If there’s a chance Snow can recover from her debilitating lupus kidney disease, it will be because of the expanded base of knowledge about lupus.
How we got to the point where doctors have a greater arsenal of drugs and information for managing lupus kidney disease is a story of diligent researchers, persistent patients, determined physicians, and increasing interest from pharmaceutical companies. Together, these factors have opened up a whole new world of lupus kidney disease care that doctors say is just the beginning.
“Anyone who lived through the decade before this one and then this decade can see that all of a sudden, we’re getting a world [of] more options,” says Gerald Appel, M.D., professor of clinical medicine and director of the clinical nephrology division at Columbia University College of Physicians and Surgeons. “One decade has just changed everything.”
Countdown to remission
Kidney involvement occurs in as many as 60 percent of those with lupus. For people like Snow, the clock is ticking. Dialysis has made her feel better, but whether her body can hold out until she gets a kidney transplant is an open question. The good news is that a lot more people being treated for lupus kidney disease are surviving than in decades past: Fifty years ago, the five-year survival rate—the period of time researchers studied patient records—was close to zero. Today, it’s more than 85 percent, according to the NIH.
That’s because in the past decade, a series of research studies and new medications have created options. When Appel started treating lupus kidney disease 35 years ago, the only medication available was cyclophosphamide. The plan of attack then was to hit hard, using high drug doses that would suppress the overactive immune system. The drug worked well—but it also caused infertility, hair loss, and an increased risk of opportunistic infection. You couldn’t stay on it too long, because it increased the risk of cancerous tumors, too.
For young adults in their 20s or 30s, the drug often killed their chance of having a family and could ruin their self-image and self-esteem with its physical side effects. And while cyclophosphamide did beat the disease into something resembling remission, it was too toxic for people to stay on it as a “maintenance” therapy. You were either on cyclophosphamide, or you weren’t on anything, leaving people subject to lupus flares.
Then, in 2002, a study out of Europe called the Euro-Lupus Nephritis Trial found that lower doses of cyclophosphamide were as effective as the traditional high doses, with reduced toxicity. This offered hope to physicians and patients alike that side effects could be minimized somewhat.
This encouraging news was followed in 2005 by a crucial study, for which Appel was a co-author, published in The New England Journal of Medicine. It showed that a newer drug called mycophenolate mofetil, or MMF (trade name: CellCept®), could be as effective as cyclophosphamide—without the hair loss, with much lower risks of infertility and cancer, and with fewer lupus flares later.
Since then, many drugs developed to treat diseases such as rheumatoid arthritis and multiple sclerosis have been studied and offered to people with lupus, including rituximab and MMF. And that means doctors like Appel and people with lupus kidney disease like Snow and Kaplan now have more choices.
But the advances are not limited to medications. Diagnosis and clinical regimens have been re-examined and revised as well. In 2004, the International Society of Nephrology/Renal Pathology Society (ISN/RPS) worked together to revise the 1982 classification system, published under the direction of the World Health Organization, that divides lupus kidney disease into six classes. The improved categorization and terminology clearly describe the various lesions that occur and will help prevent severe cases from being undertreated.
And then there are the lupus kidney disease treatment guidelines. Written in 1999, they did not take into account any of the advances of the past decade. Last year, Bevra Hahn, M.D., former chief of rheumatology at the University of California, Los Angeles (UCLA) School of Medicine, co-wrote new guidelines that are most notable for urging immediate kidney biopsies when there is any indication of kidney involvement and if the person has never been treated for lupus kidney disease before. This can help speed up diagnosis and allow treatment to begin before the disease causes irreparable scarring or other damage.
“Having a guideline about the kidney biopsy should be helpful for clinicians who don’t think about doing that immediately,” Hahn says. “It’s also helpful because third-party (insurance company) payers often won’t cover the cost of a biopsy without medical guidelines like this.”
The guidelines also lay out a path for physicians to follow when people like Snow don’t respond to typical treatments. For instance, the guidelines recommend rituximab when a person isn’t responding to MMF or cyclophosphamide, despite disappointing clinical trial results that compared the drugs. The same goes for the immunosuppressant ciclosporin (trade names: Neoral®, Sandimmune®).
Third, the guidelines recommend that everyone with lupus kidney disease be treated with the antimalarial drug hydroxychloroquine (trade name: Plaquenil®).
Finally, the guidelines are notable for what they leave out: They don’t say any treatment is contraindicated—that is, there is no recommendation against a treatment. This fits well with a disease such as lupus, which affects each person differently, and so must be treated on a case-by-case basis.
The next decade
For Snow, the next 10 years will be critical for her health. Dialysis three times a week makes her feel many times better than she felt in 2009. But it’s not enough. What she wants is to get back to being a fashion stylist. She wants to date again. She wants a purpose. She wants to contribute.
There are many reasons to think that 10 years from now, options for people with lupus kidney disease will be even broader. From where Brad H. Rovin, M.D., sits at his office at the University Hospitals at The Ohio State University College of Medicine, the future is bright.
Rovin, who is a professor of medicine and pathology and director, division of nephrology, says this year should bring at least a tentative answer to the question of whether the Euro-Lupus protocol (which found that lower doses of cyclophosphamide were as effective as higher, more toxic doses) will work in people who aren’t Caucasian. Most Caucasians with lupus kidney disease respond better to cyclophosphamide than African Americans and Latinos, so it may be that the protocol won’t work as well on African Americans and people from South America, whom Hahn says often have more severe disease.
The push to improve treatment doesn’t stop there. Researchers are studying how best to improve care for those with lupus kidney disease. Clinical trials include those looking at abatacept (trade name: Orencia®) for treatment of lupus kidney disease; other trials will try to determine whether adding the experimental immunosuppressant laquinimod to standard therapy can reduce residual inflammation, which in turn may help lead to complete remission. Right now, complete remission is rare; many treatments aim simply to stop progression of the disease.
Rovin says he is preparing to start a study of the first drug developed specifically for lupus, belimumab (trade name: Benlysta®), as a potential treatment for lupus kidney disease. “What I’m hoping we’ll see is biologics and targeted therapies that are not only less toxic to use, but also help us achieve better, more sustained, complete remissions,” he says. “And that, in and of itself, will be key to preserving kidney mass in the long run.”
Hahn hopes new classes of medications called small molecule inhibitors can not only address the symptoms of lupus kidney disease, but can also prevent the cascade of events that lead to kidney failure.
“We have some work to do, but we’ve made a lot of progress over the last few years,” she says. “A lot of people are still with us who wouldn’t have been 40 to 50 years ago. A lot more are having pregnancies and families, which was much harder to do a few decades ago. We are on the right track.”
Hope is catching
While scientists study potential treatments, Wendy Rodgers, 40, of Torrance, CA, feels like she is starting a new life. Rodgers was diagnosed with lupus kidney disease in 2000 and received a kidney transplant three years ago. In November 2012, her disability insurance company informed her it was discontinuing payments based on the dramatic improvements in her health. Between that and a tripling of her health insurance premium, she has to go back to full-time work.
She worries about her immune system, compromised by the anti-organ-rejection medications she’s on; she wonders if it will limit her job options, and if going back to work as a school teacher could compromise her health. Plus, there is that 12-year gap in employment, and a concern about managing her treatments at a time when she may not be able to afford all her medications. Continuity of care is essential for people who have had organ transplants.
Still, these are challenges Rodgers is willing to face. She hopes more people with debilitating lupus, including Snow—whom Rodgers met through a friend with lupus—will eventually be part of the working world again.
Give the gift of life: Hope through transplants
When Julie Glennon, 44, of West Palm Beach, FL, was diagnosed with lupus kidney disease and, later, kidney failure, she had to consider a kidney transplant. Her brother was deemed a good match. He was ready to begin the process of donating his kidney when her beeper from the transplant center in Jacksonville went off. A cadaverous kidney was available.
“I realized, at 31, that this kidney transplant was not going to last forever,” she says. “So I thought, ‘Let me spare my brother from this for now.’”
Organ donation is the reason Glennon and Wendy Rodgers, 40, of Torrance, CA, are still alive, and the transformation in both was instantaneous. But it is not always that simple. According to a 2007 review of previous research, as many as 11 percent of kidney donors had trouble getting life or health insurance because of their donor status. Transplant center staff in one study told researchers that 39 percent of eligible donors declined to donate for fear of being considered uninsurable. But this concern—at least as it applies to health insurance coverage—will no longer be an issue under the soon-to-be-implemented provisions of the Patient Protection and Affordable Care Act (ACA), which, starting in 2014, will prohibit health insurers from rejecting applicants due to pre-existing conditions.
There are many ways to donate an organ to someone in need. Consider contacting Donate Life for the donation center near you. “Gratitude is just a baseline of how I feel,” says Rodgers, who received her transplant two days after Mother’s Day 2009, which also happened to be her daughter’s birthday. She continually thinks of the mother of the 25-year-old woman who made the decision to donate her daughter’s organ. “That could have as easily been me making that decision,” she says. “Your life becomes more of a priority because you don’t want to let that family or person down for making that sacrifice.”
Living Well With Lupus
For Dawn Snow, lupus kidney disease is a thief—it steals your youth and your dreams, says the 33-year-old from Los Angeles. But people with lupus develop whole tool kits to protect themselves—body, mind, and spirit—from the ravages of the disease. Here are a few of them.
- Eat Well. Kidney disease requires a specific diet with low sodium, low phosphorus, and low potassium, as well as a limited intake of liquids. Wendy Rodgers of Torrance, CA, went from enjoying pizza and chocolate to eating plenty of green, leafy vegetables and avoiding most forms of dairy. “You’ve got to eat less processed food,” she says. “Thank goodness I like a lot of things!” If you have lupus kidney disease, talk to your physician or a registered dietitian about the recommended dietary guidelines and where to find meal-planning tips online.
- Laugh. The first thing I found I needed and didn’t have was laughter,” says Rodgers. “Having a chronic disease is so serious that there are not many moments that you sit around chuckling.” But she found that laughter at the Renal Support Network, which she joined as her disease progressed. She also found people who were doing something positive—like organizing “renal proms” for young people with kidney disease who could not attend their school’s event, or advocating on Capitol Hill on renal health issues—and it changed her mindset. To find local groups, check out the Renal Support Network (rsnhope.org) or call the Renal Support Network’s peer support phone line at 800-579-1970.
- Exercise. Brian Kaplan of Washington, DC, swears by exercise. In his very unscientific opinion, it “oils the joints” and keeps him moving. While it may not technically oil the joints, exercise has been found to improve energy in people with lupus. And its antidepressant effects are well known. Sometimes, Kaplan says, it’s the only way he can release the pressure he feels from having lupus kidney disease. And you might want to consider exercise programs supported by the Lupus Foundation of America, such as this low-impact routine, or an exercise program that can be tailored to your health and energy level, such as Fitocracy or Stretch Exercises, both available as smartphone apps. Be sure to discuss exercise guidelines with your physician before you get started.
- Develop Social Support. Even after everything Snow has been through—delayed diagnosis, treatment of resistant disease, kidney failure, dialysis—it’s an “attitude of gratitude” that keeps her healthy, she says. For instance, just before her diagnosis, she took custody of her sister’s newborn son. Her sister was struggling with schizophrenia and had gone off her medications during the pregnancy. Even though this was another stress, it gave Snow something she didn’t get during her own troubled childhood: unconditional love. If I hadn’t had that love to draw from, I probably would have given up,” she says. And when the prednisone made Snow psychotic, imagining she was the queen of Egypt, it was her sister who comforted her, because she understood what it was like. If my sister hadn’t been there, I would probably still be in that place,” Snow says. “I could have conversations with her without stigma, when no one else understood.”
- Give Back. Since her diagnosis, Rodgers has been part of the Renal Support Network, she campaigned for Donate Life, and she has taken part in the LFA’s national Walk to End Lupus Now™ program. After feeling alone with her disease—and so different from many of the mostly elderly people with kidney disease—finding her own supportive communities has given a new purpose to a life taken off course by lupus. “I really like to help people. That’s just how I’m built,” she says. “I feel a joy in helping others, especially others who have this disease. To me, having had my life in some ways devastated by this disease, giving back is my way of fighting back. To find a purpose within the challenge is a beautiful thing.”