Neal Birnbaum, MD, on Diagnosis and Treatment of Lupus Nephritis

In this first podcast of a series, Neal Birnbaum, MD gives an overview of lupus nephritis and discusses the diagnosis, treatment, and challenges of this complication of systemic lupus erythematosus.

Neal Birnbaum, MD, is chief of rheumatology at the California Pacific Medical Center in San Francisco, California.

TRANSCRIPTION:

Rebecca Mashaw: Hello and welcome to another podcast from Rheumatology Consultant. Today, we're inaugurating a podcast series on the subject of lupus nephritis, a serious complication of systemic lupus erythematosus. To inaugurate this podcast series, Dr. Neal Birnbaum of California Pacific Medical Center is going to give us an overview of this disease and the challenges of treating patients with lupus nephritis.

Dr Neal Birnbaum: I'm Dr. Neal Birnbaum. I'm the Chief of the Division of Rheumatology at California Pacific Medical Center in San Francisco and Clinical Professor of Medicine at the University of California San Francisco.

RM: Thank you for joining us today, Dr. Birnbaum. We're going to be talking about lupus nephritis, which is not common but probably not as rare as some people might think. How common is lupus nephritis among patients with SLE?

Dr Birnbaum: It's variable, depending on which reference you read. I saw numbers of 30%. I've seen numbers of 60% have some degree of kidney involvement in their lupus somewhere in the course of the disease. Sometimes, it's very mild and only picked up by biopsy and not requiring other treatment, but at times, it can be very progressive and leading to kidney failure and the need for dialysis or transplantation.

RM: Are there specific factors that cause some patients with lupus to be at higher risk for developing lupus nephritis, whether it's age, gender, weight, other comorbidities?

Dr Birnbaum: Not as much is known about that as we might like. We do know that some patients are more likely to have worse lupus. Worse lupus would then include more risk of renal disease. Younger patients, people of color would probably be the 2 groups that would be the higher risk. There's a lupus of the elderly in which the risk of kidney disease is quite small. If we see patients who early on have markedly abnormal serologies — their antidouble stranded DNA is very high, their complement values are very low — they're at greater risk.

RM: It seems then unlikely that there's much that either the rheumatologist or the patient can do to control for risk factors for developing lupus nephritis.

Dr Birnbaum: That's reasonably safe to say. Certainly, people should be monitored, particularly for their blood pressure, because blood pressure has an interrelationship with kidneys. Kidney disease makes blood pressure worse and vice versa. We would certainly advise all the usual admonitions about not smoking, although I can't there's a direct relationship. People should try to maintain a reasonable weight and to get some exercise. More importantly is that patients should be monitored once they are diagnosed with lupus. They should periodically have at least a urinalysis done. They should be warned what to look for, some signs that they might be developing lupus nephritis, such as unintended weight gain or puffy ankles or foamy urine when they look in the toilet.

RM: That was actually going to be my next question. What should the patient and the rheumatologist look for once the patient is known to have lupus? What kind of signals or signs might you see that are indications that they could be at risk for developing lupus nephritis? Those are certainly some key factors there. Is there anything else that you could add to that?

Dr Birnbaum: Just the comment that patients who develop nephritis as part of their lupus usually develop it fairly early in the course. The need to monitor it is more frequent in the first years. If someone gets through 5 years of lupus and they've never gotten kidney disease, there's a pretty good chance that they won't.

RM: What advice would you give your fellow rheumatologists in regard to the treatment of lupus nephritis? Is this in fact the type of disease that really does require a multidisciplinary approach?

Dr Birnbaum: Frequently, it does. It depends who your colleagues in nephrology are and how comfortable you are working with them or how much lupus nephritis you see on your own. I'm fortunate to practice at a place that has an excellent nephrology group. Several of them have worked with our group for many, many years. We're very comfortable exchanging patients. Today, the admonitions from the nephrology groups or from the American College of Rheumatology are really to biopsy earlier. In that situation, we normally get a nephrologist involved. Years ago, the nephrologists did the biopsies. Nowadays, most of them are done by the interventional radiologists, but it's still nice to have a nephrologist on board to discuss these people with because overall management is not always that simple.

RM: When is the biopsy called for? What's the indication that now it's time to biopsy this patient to take this next step?

Dr Birnbaum: The move is towards earlier biopsy because you want that information, particularly with the newer classification of lupus nephritis that came out around 2003, with the idea that people who have Class I or Class II probably don't need much aggressive management. People who have Class III, IV, and V certainly do. Class VI, which is advanced scarring, shouldn't be aggressively treated because you can't really change a scar. I would say of the patients that I have shared with our local nephrologist over the last decade or so, the ones who have gone on to, often very slowly, progressive renal failure were the individuals with long standing lupus who on biopsy did not have active inflammation but had scarring. In that situation, it's very important to maintain the blood pressure in the normal range and monitor them. Eventually, some of those patients have come to dialysis and transplantation.

RM: So transplantation is an option for patients with lupus nephritis.

Dr Birnbaum: Absolutely. Interestingly enough, when patients with lupus do come to either dialysis or transplantation, frequently the rest of their lupus feels better. For the transplanted patients, many of the drugs that are used are very similar to the drugs that we use. Mycophenolate, for instance, was originally used in transplantation and came into lupus later.

RM: When do you know it's time to do a biopsy on a patient with lupus to determine if they really are developing lupus nephritis?

Dr Birnbaum: When there's some indication, either by symptoms or by laboratory abnormalities. Has the patient suddenly gained a bunch of weight and have swollen ankles? Do they tell you they look in the toilet bowl after they urinate and it's all foamy? Laboratory studies showing a decreased serum albumin or increased protein in the urine or a rising serum BUN and creatinine or worsening of the serologies, a markedly elevated antidouble stranded DNA antibody and hypocomplementemia, any of those could be grounds to do a biopsy.

RM: How often would a rheumatologist be advised to do these serologies and to look for these biomarkers as they're working with a patient who's got lupus?

Dr Birnbaum: It's very individualized. You have to get to know the patient. Early on, we'll probably do them more frequently, maybe quarterly. If the patients had lupus for several years and they're doing well, it might be every 6 months, it might be yearly. It all depends on how the patient's doing. As I mentioned earlier, lupus often strikes a course. Whatever course it took in the first year, very often it sticks to that course in subsequent years.

RM: What treatments are available now for lupus nephritis?

Dr Birnbaum: There are a couple of baseline parameters. One is to be sure that their blood pressure is well controlled. The second is virtually everybody with lupus should be on hydroxychloroquine, Plaquenil, for chronic maintenance. At that point, what you add to it becomes individualized. If they have Class I or II lupus nephritis by biopsy, they may simply be observed. They may add a little prednisone, but often that patient does not need aggressive immunosuppressive therapy. The patients with Class V, membranous disease, often are treated with fairly high dose steroids but for a relatively short period of time. It's really the Class III, IV patients who have either focal or diffuse lupus nephritis, what they call proliferative nephritis, who tend to be treated with aggressive chemotherapy, higher dose steroids, and then the addition of steroid sparing agents, anything from cyclophosphamide, azathioprine, mycophenolate. I would say of those agents, mycophenolate— CellCept or Myfortic— has become more and more popular over the last decade as the chemotherapeutic agent or immunosuppressive agent of choice. For patients who have not responded to that regimen, now we have the recent addition of 2 FDA approved products, one, belimumab, Benlysta, and the other one, Lupkynis, which is the calcineurin inhibitor. Those are generally used as an add on to patients who are failing steroids and immunosuppressives.

RM: Any last words for your colleagues in rheumatology about the challenges of working with patients who have lupus nephritis?

Dr Birnbaum: They're very challenging patients. They can be the most difficult patients that we deal with because the disease is so heterogeneous. It's entirely reasonable to see patients with nephritis in consultation with a nephrologist and to act jointly in deciding what the best course of therapy is for an individual patient.

RM: Thank you very much for taking the time to talk with us today. I really do appreciate it.

Dr Birnbaum: Thank you for having me.

RM: Thanks for joining us today for this podcast. Look for more podcasts on lupus nephritis coming soon.