Chat Transcript for Dr. Ellen Ginzler, March 21, 2007
Moderator
Good afternoon. The Lupus Foundation of America is pleased to welcome Dr. Ellen Ginzler. Dr. Ginzler is a Professor of Medicine and Chief of Rheumatology at the Downstate Medical Center, State University of New York (SUNY) in Brooklyn.
Moderator
She earned her medical degree from Case Western Reserve University School of Medicine in Cleveland, Ohio, USA, and earned her masters in public health from the Yale University School of Epidemiology and Public Health in New Haven, Connecticut.
Moderator
Dr. Ginzler in a Fellow of the American College of Physicians and serves on the Board of Directors of the American College of Rheumatology’s Research and Education Foundation, among many other professional and institutional responsibilities. An active educator, researcher and author, Dr. Ginzler has published more than 80 scientific articles and book chapters in the field of systemic lupus erythematosus. Her particular area of clinical and academic focus is lupus and lupus nephritis, specifically its clinical course, treatment and epidemiology – with particular regard to outcomes and sociodemographic influences.
Moderator
We welcome Dr. Ellen Ginzler, and thank her for joining us this afternoon.
Moderator
The first question comes to us from Ohio. What are symptoms of kidney involvement that we should recognize at home?
Dr. Ginzler
Frequently the first symptoms of kidney involvement in lupus are non-specific. In the beginning kidney function is usually normal, but it is common to feel fatigue or to have other symptoms of active lupus, such as joint pain or swelling, hair loss, or a butterfly rash. As the kidney involvement continues, it is common to spill protein in the urine. This can lead to fluid retention and leg swelling. Some people who do not even have a diagnosis of lupus yet may notice leg swelling, which leads them to see a doctor, who may make a diagnosis of lupus.
Moderator
Our next question is from Maryland. Is there any routine testing that can warn the physician and patient of the beginning of renal failure before the damage is worthy of Prednisone or chemotherapy?
Dr. Ginzler
Every patient with lupus should have screening tests of kidney function, including blood urea nitrogen (BUN) and serum creatinine. These blood tests show how well the kidneys are functioning to eliminate wastes. The urine should be examined to look for protein and blood cells, called urine sediment, which may be due to inflammation in the kidneys. If these tests are normal, they are usually repeated at intervals of about 3-6 months. If lupus is active in other systems besides the kidneys, or if there is evidence of protein or blood cells in the urine, these tests should be repeated much more frequently – usually every month. A small amount of worsening can be detected before severe changes occur. Lower doses of prednisone or other medications may reverse the abnormalities if detected early.
Moderator
Oklahoma asks ... Is there anything I can do to prevent getting nephritis? What should I look for, if anything?
Dr. Ginzler
In addition to monitoring kidney function and urine protein levels, it is appropriate to monitor anti-double stranded DNA levels and complement levels in the blood. Anti-DNA antibodies are very specific for lupus, and are often present in the blood with active kidney inflammation. An increasing amount or titer of anti-DNA antibodies in the blood suggests that lupus kidney disease is flaring, but some people with lupus will make these antibodies without having detectable kidney disease. Although it may not be possible to prevent a flare of kidney disease, detecting it early is important in planning the proper treatment.
Moderator
Missouri wants to know ... I've read that kidney involvement occurs in 30-50% of lupus patients. Is this a true estimate? Those figures seem high. Should I look forward to kidney problems?
Dr. Ginzler
Kidney involvement can actually occur in more than 50% of lupus patients. In part, the diagnosis depends upon how carefully one looks for protein or blood cells in the urine, and what level of urine protein and kidney function is considered to be abnormal. About 30-40% of lupus patients will develop moderate to severe kidney disease.
Moderator
This question comes from Florida. Once you start with kidney involvement (Nephritis) is it a sign that eventually you will have kidney disease?
Dr. Ginzler
Once you start to show signs of lupus nephritis, treatment may result in a return to normal kidney function and improvement in urine protein and sediment. In patients who have ever had active lupus nephritis, there is a greater chance that another flare of active kidney disease will occur in the future.
Moderator
Our next question comes from Michigan. If proteinuria is not treated, will this result in permanent damage to the kidneys? What level of proteinuria is dangerous?
Dr. Ginzler
If proteinuria becomes chronic, either because it is untreated or does not respond to treatment, it can result in permanent damage to the kidneys. In some patients this may eventually lead to kidney failure. It can also increase the risk for infections and high cholesterol levels, which are a risk factor for coronary artery disease and strokes. Other patients seem to be able to have chronic proteinuria without symptoms or poor kidney function. If the urine protein level is above 1000 mg/24 hours, I like to monitor kidney tests at least every 3 months. Some of the investigational treatments being studied in clinical trials now may be more effective in decreasing proteinuria.
Moderator
North Carolina wants to know ... How serious can your kidney problem get with lupus?
Dr. Ginzler
Even with treatment, some patients with lupus nephritis will not improve. Kidney function may continue to deteriorate and lead to kidney failure that requires dialysis. Kidney failure can occur during a flare-up of active nephritis, or it can develop slowly over many years due to continued scarring of the kidneys even after the signs of an active flare have subsided.
Moderator
Another question from Ohio. When do you recommend having a kidney biopsy, i.e. what lab results -- levels of protein, etc. would cause you to feel that a biopsy would be necessary or useful?
Dr. Ginzler
Not all doctors agree on the proper time to do a kidney biopsy. Some believe that it should be done as soon as any abnormalities of kidney function or urine analysis are found. Others believe that mild abnormalities can be treated without a biopsy. It is important to think about what information will be obtained from the biopsy, such as the amount of active inflammation vs. scarring that is present. We also look for specific types of changes in the kidney (defined as World Health Organization – WHO – types 1-5). The WHO classification gives information used to determine the types of treatment and chances of achieving a remission of the active nephritis.
Moderator
We have a question from Colorado. Do the kidneys have the ability to regenerate or heal themselves from an attack of Lupus nephritis if the patient goes into remission?
Dr. Ginzler
Treatment is designed to decrease or eliminate the inflammation that occurs with active nephritis. Kidney tissue does not regenerate, but it can return to or maintain normal function.
Moderator
New York has a question. Can you discuss Cyclosporine vs. CellCept? How about Cytoxin vs. Rituxan? I was on CellCept my nephrologists wants to switch to Cyclosporine. My rheumatologist wants to start Cytoxin but my nephrologists would like me to try Rituxan.
Dr. Ginzler
There are many questions about treatment for lupus nephritis. There are a number of options, and not all rheumatologists and nephrologists agree. Most would start with prednisone, although the dose may vary depending upon the severity of symptoms and amount of kidney dysfunction. For moderate to severe nephritis, the most common choices in addition to prednisone are either cyclophosphamide (Cytoxan) – usually given as an intravenous infusion, or oral mycophenolate modetil (CellCept). CellCept tends to have fewer side effects, and has not been shown to cause infertility. Whichever drug is selected first, the other may be prescribed if the first does not work.
Moderator
Michigan has another question. I had a kidney biopsy performed in May 2001 because of too much protein in my urine. As a result, I was prescribed CellCept for approx. 2 years. I was then taken off the CellCept because tests showed that the protein in my urine had decreased. What are the chances of this happening again?
Dr. Ginzler
We do not know for sure how long a patient should be treated with CellCept or IV Cytoxan after going into remission, but most experts believe it should about 2-3 years before discontinuing the maintenance regimen. We do not know how long it can take for a flare-up to occur, but it can be as soon as a few months, although other lupus patients may not have another episode of active nephritis for many years. It is essential that kidney function and urine protein levels, as well as serum complement and anti-DNA levels, be closely monitored after the medications are stopped, probably every month for 3-6 months, then every 2-3 months. This allows the doctor to detect a flare-up even before there are any symptoms, and to restart treatment quickly.
Moderator
Joining us is California. What do you think of CellCept as a medication? What new medications are possibilities in treating lupus?
Dr. Ginzler
Unlike Cytoxan, which has been used to treat lupus nephritis for more than 25 years, CellCept has been used for only about 8 -10 years. Neither medication has been approved by the FDA for treatment of lupus. I believe that CellCept is just as likely, and probably more likely, than IV Cytoxan to be effective in resulting in a complete or partial remission of lupus nephritis, and that it has less side effects than Cytoxan. Still, there are many patients who do not have a significant benefit from either drug. There are many new agents being developed and tested as treatments for lupus in general and specifically for lupus nephritis. Most of these new drugs can only be obtained by participating in a clinical trial to find out whether they will prove to be effective without side effects.
Moderator
Michigan has a question. I was treated with Rituxan for lupus nephritis and have been in remission since, for 3 years. How long do you predict this will work?
Dr. Ginzler
Like CellCept, Rituxan is available by prescription but has not been approved by the FDA for treatment of lupus. By interfering with certain immune functions, it is designed to result in a long-lasting remission of disease activity. In different reports, this remission may last for as short a time as several months to as long as several years. Clinical trials are going on now to get better information about the benefits and side effects of Rituxan as a treatment for lupus.
Moderator
Our next question comes to us from Indiana. Is there anything other than a drug that one could use or do for the kidney to stop leaking protein?
Dr. Ginzler
There are actually other medications which decrease the protein spillage in the urine. The most common are called ACE inhibitors, generally used to treat high blood pressure, but they can also be used in people with normal blood pressure.
Moderator
From Connecticut. I am 25, and have been living with lupus nephritis for 4 years. I just got married, and am getting ready to start a family. How can I prepare myself for pregnancy with lupus nephritis?
Dr. Ginzler
When you have lupus, it is always best to plan in advance for pregnancy, and to discuss the plans with your rheumatologist or nephrologist. It is best to begin trying to become pregnant when your lupus is in remission or only mildly active. It is easier to conceive when you are relatively well, and it is best for the baby if you do not require many medications, especially high dose steroids or immunosuppressive agents. Some medications may need to be stopped well in advance of becoming pregnant, while others, such as Plaquenil and Imuran, are generally considered to be safe during pregnancy. There are also specific antibody tests that need to be done, such as anticardiolipin antibodies, the lupus anticoagulant, and anti-Ro and La antibodies. These antibodies in the mother can influence the proper development of the growing fetus.
Moderator
California asks the following. Is there any advice that you can offer for the family in means of trying to give support to someone who is about to start dialysis?
Dr. Ginzler
Family support is very important for all patients with lupus, but especially when one needs to begin dialysis. Kidney failure is often accompanied by symptoms such as fatigue, a general sense of weakness, anxiety, and insomnia, so patients may need physical help to get through their activities of daily living. Going to dialysis, usually 3 times a week, is also very time-consuming and causes a major change in life style. Help in getting to treatments, as well as emotional support are essential to making the adjustment. When a lupus patient knows that dialysis will be required soon, it is not too early for family members to think about whether they would be willing to consider giving the gift of a kidney transplant.
Moderator
The Philippines has a question. I've had a kidney transplant 16 years ago due to lupus nephritis. I had a recurrence 2 years ago. What can I do to prevent recurrence of my lupus nephritis in the future? How long can my transplant hold on with the recurrence of my lupus nephritis?
Dr. Ginzler
Many people asked about kidney transplants. Twenty years ago we believed that kidney transplants were not successful in patients with lupus, but currently we know that the prognosis is usually very good after a kidney transplant. It is important not to plan the surgery until any infections or other medical problems are treated. The medications used to prevent rejection of the transplant (CellCept, Imuran, cyclosporine, tacrolimus) also work to prevent the development of active lupus nephritis in the transplanted kidney. One study reported 10 years ago found that 10% of patients did have a recurrence of lupus nephritis, but this outcome is probably much less common now with newer anti-rejection drugs.
Moderator
Here's an interesting question regarding stem cell treatments. Can lupus nephritis or other severe features of lupus be cured with a stem cell transplant?
Dr. Ginzler
The goal of a stem cell transplant is to eliminate the cells from the bone marrow which cause the immune abnormalities leading to active lupus, and then to allow the bone marrow to recover with normal functioning immune cells. In order to do this, very powerful drugs need to be given first, essentially destroying the bone marrow. The risk for severe infections and other side effects is very high, and the procedure is extremely expensive and difficult for a patient to undergo. As a result, the initial enthusiasm for this form of treatment has decreased substantially.
Rosie
If a person is down to 25% kidney function, is it time to find a match? Does a blood match from a relative ensure that the tissues will match?
Dr. Ginzler
Some people with only 25% kidney function remaining may continue to feel well with proper diet and exercise for as much as 4-5 years, while others will progress within a year or 2 to kidney failure with symptoms of fatigue, poor appetite, difficulty sleeping, and general muscle aches and weakness. Transplants from related donors have a better chance of being successful, but with the newer anti-rejection drugs, they do not have to be a perfect match. The good thing about a live donor transplant is that it can be planned in advance, and you can make sure that both the donor and recipient are in the best possible medical condition when the surgery takes place.
ggl
What specific levels of protein and red cells in the urine would you consider signs of remission that would show the current drug therapy is working?
Dr. Ginzler
We consider complete remission to occur when the level of protein in the urine is less than 500 mg per 24 hours, and there are fewer than 5 red blood cells and/or white cells in the urine, with no cellular casts. In fact, absolutely normal kidney function probably means that the proteinuria is below 200 mg/24 hours. On the other hand, a partial remission may also indicate that a patient has responded well to treatment. Some doctors consider a remission to occur if the protein spillage goes from levels that indicate nephrotic syndrome (more than 3500 mg/24 hours) to less than nephrotic levels. Others feel that a decrease of 50% is consistent with significant improvement.
whootie
Are anti-DNA levels always positive in lupus?
Dr. Ginzler
Anti-DNA antibodies are very specific for lupus, but do not have to be present. Some people with lupus have anti-DNA antibodies all the time, even without any other signs or symptoms of lupus nephritis. Some lupus patients with nephritis may not have anti-DNA antibodies, especially if they have milder forms of lupus kidney disease. In most patients, the level of anti-DNA antibodies correlates with the amount of inflammation and degree of active kidney disease. Often the anti-DNA levels increase before a flare-up. This helps us to detect the flare early and start treatment.
Michelle
How common is infertility as a side effect from Cytoxen treatment?
Dr. Ginzler
The drug which is most often associated with infertility is Cytoxan. The risk of developing infertility is directly related to increasing age and the duration that Cytoxan is given. If a woman in her teens, 20s to 30s gets a single six month course of Cytoxan, the chance of infertility is probably less than 10%.
Tia
Can CellCept be used as a "maintenance" drug during periods of low nephrotic activity?
Dr. Ginzler
The evidence so far from two controlled studies, one in Miami Florida and the other in Hong Kong, suggests that CellCept is a good drug for maintenance therapy to prevent flares of lupus nephritis after the active disease has been successfully treated with either Cytoxan or Cellcept. Two large studies are now in progress to provide further information about the effectiveness of CellCept compared to Imuran as a maintenance therapy.
KL
How prevalent is cancer after treatment with Imuran?
Dr. Ginzler
Many patients are concerned about the risk of cancer after having lupus for a long time, or after being treated for many years with immunosuppressive drugs such as Imuran. A study including almost 10,000 patients with lupus found that the risk to develop cancer is mostly related to lymphomas. Smoking increases the risk for cancer in lupus patients, just as it does in other people. So far, there is no good evidence for a link between Imuran and cancer in lupus patients.
EB
How old is too old for a kidney transplant?
Dr. Ginzler
A patient's general medical condition is probably more important than their chronological age in deciding whether they are a good candidate for a kidney transplant. The same is true in deciding whether the potential donor is appropriate.
Tia
How long can someone be on dialysis before requiring a transplant?
Dr. Ginzler
Some patients feel very well on dialysis and adapt to the life-style changes very well. I have patients who have been o dialysis for more than 15 years and do not wish to consider having a transplant. Others may have chronic problems such as infections or clotting of their graft site for dialysis, or may just not want to have to dialyze 2 or 3 times a week. It is an individual choice based on medical condition and life style.
Moderator
How does the body produce complements (specifically C3 and C4)? Why do these numbers fall in lupus nephritis?
Dr. Ginzler
Complements are a group of proteins made by the liver. They are activated by inflammation and combine with antigen-antibody complexes which precipitate in tissues and result in more inflammation. The complement components are used up during this process, so the levels we measure in the blood decrease, especially during active kidney disease.
Dr. Ginzler
The questions all of you asked were excellent, and I enjoyed answering them. Please remember that treating lupus is a partnership between patients, family members and friends, and doctors – particularly rheumatologists and nephrologists. Many advances in treatment are on the horizon, especially because of new clinical trials. Your participation in these trials should hasten the approval of new drugs for lupus, and probably also help us to a better understanding of why lupus develops.
Moderator
That is all the time we have for today’s chat. Thank you to Dr. Ellen Ginzler for joining us today.
Moderator
Please join us Wednesday, April 11 at 3 p.m. EST for our guest Dr. Laura Coleman from the Marshfield Clinic Foundation. Dr. Coleman will discuss diet and nutrition for people with lupus.
Connect with Us: