Lupus Nephritis and Reproductive Health: Part 2

In the second podcast of a 2-part discussion, Dr Sammaritano discusses the challenges of caring for patients with lupus nephritis during pregnancy, including the safest medications to use and how to manage flares of disease.

Lisa Sammaritano, MD, is a professor of clinical medicine at Weill Cornell Medicine and an attending rheumatologist at the Hospital for Special Surgery in New York City.

TRANSCRIPTION:

Rebecca Mashaw:  Hello, and welcome to another podcast from Rheumatology Consultant. I'm your moderator, Rebecca Mashaw. Today, we continue our conversation with Dr. Lisa Sammaritano about caring for patients with lupus nephritis who wish to become pregnant or are pregnant, including how to potentially avoid complications and how to manage complications when they do arise.

As a rheumatologist, what, if anything, do you do differently when you're working with patients who are pregnant and have lupus nephritis as opposed to patients who have lupus but do not have the kidney involvement? Are there particular complications or symptoms that you watch for? Do you see them more frequently?

Dr. Lisa Sammaritano:  Yes and yes. Actually, let me take a step back from answering that question to just say, first, I think that we do our utmost to ensure that patients will not have lupus nephritis that is active during pregnancy.

As a part of that, we counsel our patients from early on before they tell us they want to become pregnant, so that they understand that if the time is right for them to consider pregnancy, that their lupus, especially their nephritis if they've had nephritis, needs to be quiet.

That is because the risk of lupus nephritis and the risk of other manifestations of active lupus, that really impacts the outcome of pregnancy, both for the mother and the child. Having active lupus when conceiving—and again, now I'm talking about any significant lupus activity, I'm not talking about a little rash here or there but significant disease activity—increases the risk of miscarriage, risk of pregnancy loss increases, the risk of early delivery, intrauterine growth restriction or babies that are small for their gestational age. And lupus itself, as well as any form of kidney disease, increases risk of preeclampsia.

We really try hard to educate our patients and encourage them to discuss this with us so that we can agree together on timing and medications. Now, that is the ideal situation. Things don't always work out that way.

In a patient who has a history of lupus nephritis but overall quiet disease, of course, we follow carefully in terms of symptoms of active lupus, frequent checks of urine for protein, frequent checks of complement levels and DNA. We do advise that they see a maternal‑fetal medicine specialist, and that they be followed more carefully with monitoring throughout the pregnancy, as compared to patients with lupus and no history of nephritis where we will follow them in much the same way but probably a little less obsessively, a little less closely.

What about the patient who unexpectedly becomes pregnant when she has active lupus nephritis, or is pregnant and newly develops lupus nephritis, or recurrence of prior nephritis? That's one of our most challenging scenarios.

In that setting, we will treat with high‑dose corticosteroids because we do feel that prednisone and prednisolone carries minimal risk for the fetus. Of course, high‑dose steroids will increase a woman's risk of high blood sugar, high blood pressure. Again, we will use it if and when we have to, and we will start that patient on azathioprine.

We might consider adding tacrolimus. We might consider, if things are quite serious, giving intravenous pulse corticosteroids and even, as I mentioned before, giving intravenous rituximab during the course of the pregnancy.

Another frequent complication is that patients who have lupus and renal disease, as well as those who have antiphospholipid antibodies — another really important risk factor for pregnancy complications in lupus —those patients are at much greater risk for preeclampsia and oftentimes for earlier onset of preeclampsia.

Sometimes, we will have patients who, at the end of their second or early third trimester, may develop a new onset of protein in the urine with high blood pressure. How do we know if that is preeclampsia or if that is reoccurrence of their lupus nephritis that had been quiet during the early part of pregnancy? It's challenging and ultimately can be impossible to decide, in part because sometimes they occur together, but what we do in that situation is it's best to look at other measures that might give us a clue.

For example, rising levels of anti‑DNA antibodies or falling levels of complement are consistent with active lupus, presence of other lupus symptoms such as recurrent rash, hair loss, joint inflammation with swelling. Those all suggest that there is ongoing active lupus.

When we can't decide, we may end up treating for both. That sometimes means treatment for preeclampsia, which ultimate treatment, of course, is delivery, and treatment for lupus nephritis unless everything comes down and goes away once the patient is delivered.

One thing that is helpful to remember is that preeclampsia, by definition, only occurs in the second half of pregnancy. That means after 20 weeks. If one of our patients at 14 or 15 weeks of pregnancy develops high blood pressure and a marked increase in urinary protein, we assume that that's lupus nephritis.

I will say, although I have not done this, there may be a role sometimes, especially early in pregnancy, for kidney biopsy to assess the severity and activity of the lupus nephritis. There are studies that report that in some cases that may change patients' decision‑making in terms of the pregnancy.

That's an unusual case because again, early in pregnancy, we usually can tell. Later in pregnancy, we do our best. Even though these biopsies can be done later in pregnancy, most often, they're not just because there is still the risk of a biopsy and the concern of adding that risk to all of the other risks that the patient is facing.

RM:  To wrap this up, what advice do you have for your fellow rheumatologists who may be caring for patients with lupus nephritis who are or want to become pregnant, who were considering fertility treatment if that's an issue, who are making choices about contraception and whether to even attempt to become pregnant? What's the best thing they can do for those patients?

Dr. Sammaritano:  Well, I think there is a series of questions that it's important to run through. The first is, can this patient safely carry a pregnancy? And although the answer is usually yes, occasionally it's no.

Sometimes, our patients with previous lupus nephritis, even though it may be well‑treated and completely inactive now, may be left with kidney damage that has left them with a lowered GFR or filtration rate that is not consistent with being able to safely carry a pregnancy.

Normal serum creatinine is less than 1. When women are pregnant, their creatinine usually drops to about 0.5. That's because, with all of the extra blood volume that a woman needs to circulate through not only her own circulation but the placenta, the kidneys are working overtime and are filtering about 50% more blood volume than they normally do.

So you can imagine if the patient has a creatinine of 2 or higher, which indicates a real drop in their normal filtration rate, that kidney will be overwhelmed with the demands of pregnancy and may well then have a further deterioration in kidney function, leading even to the possibility of kidney failure.

That first question while usually fine, occasionally, there will be a patient who needs to be counseled about that.

You mentioned fertility therapies. One thing that these patients have the option of pursuing would be to undergo an IVF cycle and then have a surrogate carry the pregnancy for them because their renal function is usually not threatened by a brief IVF cycle. It doesn't have the same demands on the kidneys.

Of course, there are many issues around that including financial and legal, but if that is an option, that may be a way that a woman with low kidney function can have a biological child. Once you get past that question, you need to look at the activity of the lupus.

If it's active, you need to tell the patient, "Sorry, we need to redouble our efforts to control your active lupus and in 6 months, we can revisit this question,” again, ideally. The other issues are, assess how significant any prior kidney issues have been. Look at antibodies. I know it's not the focus of our discussion today, but there are important antibodies to look at including the antiphospholipid antibodies I mentioned, which can increase risk of miscarriage or pregnancy complications, as well as anti‑Ro and La antibodies, which carry their own risk of neonatal lupus developing in the developing fetus. It's important to look at those.

The final point, I think, is to have a clear discussion with the patient and her partner, if possible, about the risks of pregnancy for her, given her particular disease, activity, damage if that has been present, and antibodies, and then move forward from there.

It's important to collaborate with both a nephrologist for those with a history of nephritis as well as, of course, a maternal‑fetal medicine specialist. I think that with that team approach—and the team includes the patient who is now educated, aware of the risk, making her decisions based on what we estimate her risk to be—I think that's the best way to go forward and have a successful pregnancy.

I will say that, sometimes, it takes longer than anyone would like. I have had patients with nephritis who have gone through this process and went on to azathioprine, and then did flare, and had to go back on mycophenolate. Yet ultimately, this particular patient that I'm thinking of, it took us 3 to 4 years to get her to the point where she delivered a baby.

She now has two young children, and her kidney function is fine because we paid attention. We monitored, and we pulled back and treated her again when we had to. And she was willing to defer her plans for pregnancy so that when she did have a pregnancy, it would be safer for her and for the baby.

RM:  The story as always is healthy the mother, healthy baby?

Dr. Sammaritano:  Yes, I think so.

RM:  Thank you so much for spending this time with us. We really appreciate you sharing your knowledge and your insights.

Dr. Sammaritano:  Thank you. It's been a pleasure.