Q&A: What to know about pregnancy for women with kidney disease
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Key takeaways:
- Despite misconceptions, women on dialysis do become pregnant and women with a kidney transplant can safely breastfeed.
- Women should wait at least 1 year after transplant before attempting to conceive.
When counseling women with kidney disease about pregnancy, nephrologists and women’s health providers must emphasize intentionality.
That means consistent use of a reliable birth control method and discussions with the health care team before attempting to conceive — whether a woman is on dialysis or is a kidney donor or recipient.
“We need shared decision-making with women rather than a paternalistic attitude,” Silvi Shah, MD, MS, FASN, FACP, associate professor in internal medicine at the University of Cincinnati College of Medicine and a specialist in women’s health in kidney disease, told Healio. “We have to remember that childbearing is important, and we have to counsel women with kidney disease about all the risks and then support them in whatever decision they take.”
Pregnancy for women with kidney disease is considered high risk, Shah said. She spoke with Healio about the relationship between kidney function and pregnancy, considerations for women with a kidney transplant, common misconceptions about conception and breastfeeding, and more.
Healio: First, do women with kidney disease have special fertility considerations?
Shah: Women with kidney disease do have special fertility considerations. Hormonal changes occur with kidney disease. Kidney disease is associated with impairment and disruption of the hypothalamic-gonadal axis. This is responsible for decrease in the levels of estrogen, progesterone and testosterone. And at the same time, there is increase in the levels of prolactin and luteinizing hormone. The absence of surge of luteinizing hormone and gonadotropin-releasing hormone ultimately results in anovulation and impaired fertility.
Women with kidney disease, especially women who are on dialysis, have menstrual abnormalities. Women with chronic kidney disease also have menstrual abnormalities, but, interestingly, a kidney transplant restores fertility. Menstrual cycles can return within 2 months of getting a kidney transplant, and fertility may return as soon as 6 months.
Healio: Should women wait a certain amount of time following a transplant before attempting to conceive?
Shah: Usually, we ask women to wait at least 1 year because we want to make sure their graft function is stable, they do not have any recent episodes of rejection and they are not on any medications that are teratogenic and can be harmful for the baby, especially in the first 6 months when they also receive some sort of prophylaxis, which is teratogenic.
Nationally, with most of the kidney transplant programs, women are on triple-drug immunosuppression: a calcineurin inhibitor, which can be tacrolimus, the most commonly used calcineurin inhibitor, or sometimes cyclosporine; an antiproliferative agent, which is typically mycophenolate; and prednisone. Of these three drugs, mycophenolate can cause birth defects and is not safe during pregnancy.
If a woman wants to get pregnant, we change mycophenolate to azathioprine, a slightly weaker immunosuppression agent. Switching should take place at least 6 weeks before attempting planned conception.
So, when I have a patient who tells me “I want to get pregnant,” my first concern is that they wait at least 1 year after the transplant. The second concern is they have minimal risk factors, which means they have a stable creatinine less than 1.4 mg/dL, they do not have any recent episodes of rejection, they have minimal proteinuria, blood pressure is optimally controlled and they’re on this optimal immunosuppression for at least 6 weeks before starting to try to get pregnant.
Healio: So, it must be important for women always to be using contraception unless they are trying to get pregnant.
Shah: Absolutely. They have to be on birth control. This is something we’re trying to raise awareness for nationally through meetings, conferences [and] talks, that contraception is important.
In the past, it was believed that women on dialysis cannot get pregnant because of impaired fertility. Last year, we published a study that showed for the first time that women on dialysis have a high rate of pregnancy — 18 per 1,000 person years. Our hypothesis was that most of these pregnancies are unintentional and none of these women are using birth control because it is just believed that they cannot get pregnant. We were able to capture all conceptions, regardless of the outcomes; it may have ended up in a miscarriage or abortion, but we were still able to capture the pregnancy incidence, and the pregnancy incidence was high.
So, yes, women on dialysis should be on contraception. Women with chronic kidney disease should be on contraception. And, importantly, women with kidney transplant should be on contraception if they want to prevent any unintentional pregnancies. This is something we tell them right at the time of their transplant evaluation: You need to start contraception as soon as you get a kidney transplant before you decide to proceed with pregnancy.
Healio: Are there reasons to choose one form of contraception over any other?
Shah: We have different contraceptive options to choose from, but what we have to keep in mind is their failure rate — especially now with changes in reproductive health laws — and any side effects. We tell all our patients they should not use barrier contraception because of a high failure rate.
The top contraceptive method we recommend is intrauterine devices because their failure rate is low, less than 0.1%, and they are usually safe. The next is progesterone-only methods, which, again, have a low failure rate and have lower incidence of side effects.
Combined oral contraceptives, which contain both estrogen and progesterone, can be used, but we have to be careful because most transplant patients have a higher cardiovascular risk just because of the history of kidney disease. They may have hypertension, a history of blood clots, deep vein thrombosis or lupus nephritis. In all those cases combined, oral contraception would not be the first choice.
Healio: Once a woman is pregnant, does pregnancy affect kidney function?
Shah: Pregnancy does impact kidney function, in general, because there is hyperfiltration, which occurs during pregnancy, there is increase in GFR. Usually, for women with normal kidney function, creatinine level falls below the baseline during pregnancy, especially in the first and second trimesters. If they had a baseline creatinine of 1 mg/dL, during pregnancy, it would be 0.6 mg/dL to 0.7 mg/dL.
Now, the guidelines we have regarding diagnosis of chronic kidney disease — the KDIGO guidelines and others — do not take pregnancy into account. We don’t have a lot of knowledge on how to define chronic kidney disease or even acute kidney injury with pregnancy. However, we do know creatinine falls, so we have to take that into account when we are evaluating kidney function of women with kidney transplants. Even normal creatinine levels may indicate an acute kidney injury because there is decrease in creatinine during pregnancy.
Healio: Does kidney disease, transplantation or donation present elevated maternal or fetal risks?
Shah: Kidney transplant does increase risks for adverse maternal and fetal outcomes. This is a high-risk pregnancy. Kidney transplant increases risks for caesarean section and preeclampsia. The risk for preeclampsia is much, much higher for women with kidney transplant compared with the general population.
There is also an increase in the risk of worsening of kidney function with pregnancy, and that, again, depends upon the baseline creatinine level. Studies have shown — not in the transplant population, but in patients with chronic kidney disease — that if your creatinine was more than 2 mg/dL, you had a 30% chance of needing dialysis by 12 months postpartum.
Adverse fetal risk also is higher for women with kidney transplants. There is higher risk of preterm birth, low birth weight, intrauterine growth restriction and perinatal mortality with kidney transplant compared with the non-transplant population.
Healio: Does kidney donation present any elevated risks?
Shah: Kidney donation also increases risks, but these are much less compared with the kidney transplant population. Studies have shown that kidney donation increases the risk for preeclampsia and gestational hypertension by 2.4-fold compared with women who have not donated a kidney.
Healio: Finally, in the postpartum period, are there any special considerations with breastfeeding or follow-up?
Shah: This is an important question. Breastfeeding is safe with kidney transplant.
I was surprised to see that even right now it is not widely known that breastfeeding is safe. Even in the kidney care community, it is perceived that breastfeeding is not safe. I recently had a patient who was admitted to a community hospital, and she was told not to breastfeed, that it’s not safe.
It is important for us to highlight that breastfeeding, if the patient is on optimal immunosuppression — calcineurin inhibitors, azathioprine and prednisone — is safe. We do not have a lot of data on mycophenolate and breastfeeding.
It is important for us to counsel women about pregnancy risks and have a close follow-up
with a multidisciplinary team. These are high-risk pregnancies, and women will need a maternal fetal medicine specialist and a neonatologist in addition to a transplant nephrologist. The women should deliver and be followed in a tertiary care center that has a neonatal intensive care unit, because the majority of these babies are preterm.
Reference:
Shah S, et al. J Am Soc Neph. 2023:doi:10.1681/ASN.20233411S152a.
For more information:
Silvi Shah, MD, MS, FASN, FACP, can be reached at shah2sv@ucmail.uc.edu; X (Twitter): @silvishah.
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