Daniel M. Keller, PhD

November 20, 2014

PHILADELPHIA — For women who have undergone kidney transplantation and are receiving antirejection drugs, pregnancy is safe and outcomes are good, according to new data from the National Transplantation Pregnancy Registry.

"We tell women that if they have stable transplant function and they're on medications that are compatible with pregnancy, we see very low rates of rejection and graft loss within two years of pregnancy," said Lisa Coscia, RN, from the registry at the Gift of Life Institute in Philadelphia.

"The babies are born a little bit early, around 36 weeks, and weigh about 5.5 pounds, but overall do very well," said Coscia, whose team conducted two studies presented here at Kidney Week 2014.

In the first study, she and her colleagues evaluated 1514 pregnancies in 895 women who had undergone kidney transplantation and were receiving azathioprine, cyclosporine A, or tacrolimus.

The three immunosuppressants were introduced at different times and, therefore, have been used in different eras. The study covers the period from 1967 to 2013, and all three drugs were still being used to some degree in 2013.

Table 1. Immunosuppressant Use in the National Transplant Registry

Variable Cyclosporine Group Azathioprine Group Tacrolimus Group
Years of use 1982–2013 1967–2013 1993–2013
Women, n 466 240 189
Pregnancies, n 778 441 295
Babies born, n 808 456 303

 

"The incidence of rejection and of graft loss were comparable" in the three treatment groups, Coscia told Medscape Medical News. However, there was significantly more hypertension during pregnancy in women treated with cyclosporine than in those treated with azathioprine or tacrolimus (61.5% vs 26.1% vs 51.0%; P < .001)

In addition, serum creatinine levels were significantly higher in cyclosporine-treated women than in women treated with either azathioprine and tacrolimus.

Table 2. Serum Creatinine Levels

Stage of Pregnancy Cyclosporine Group, mg/dL Azathioprine Group, mg/dL Tacrolimus Group, mg/dL P Value
Before 1.4 1.1 1.1 <.01
During 1.4 1.2 1.2 <.01
After 1.6 1.2 1.3 <.01

 

There were more planned pregnancies in the tacrolimus-treated women than in women treated with either cyclosporine or azathioprine (73% vs 58% vs 59%; < .01). Coscia speculated that in recent years, as tacrolimus use became more common, more women might have planned their pregnancies and replaced mycophenolate mofetil — known for its association with pregnancy loss and congenital malformations — with another therapy.

There were no significant differences between the three groups in terms of rejection that required treatment during pregnancy (range, 0.5% - 1.4%) or graft loss in the 2 years after pregnancy (range, 4.2% - 7.2%). Live births ranged from 77.6% to 81.6%, and miscarriage rates were similar in the study participants and the general population.

About half the babies in each group were born just shy of 37 weeks of gestation, which would qualify them as premature.

Birth defect rates were no greater than in the general population in the United States, and longer-term follow-up studies on the children show that they do well in terms of learning and behavior.

The mother's glomerular filtration rate before conception is the key to a successful pregnancy, researcher Serban Constantinescu, MD, from the Temple University School of Medicine in Philadelphia, told Medscape Medical News.

Dr. Constantinescu presented another study by the team at the meeting. In it, they showed that as the glomerular filtration rate decreased during pregnancy, the incidence of graft rejection and hypertension rose.

A lower glomerular filtration rate was also associated with higher rates of graft loss in the two years after pregnancy, a decrease in live births, and an increase in low-birthweight babies and miscarriages.

Coscia explained that the Gift of Life Institute recommends multidisciplinary care — involving obstetricians skilled in managing high-risk pregnancies and, if possible, the transplant center — for transplant patients who become pregnant.

She said the registry and publications from it are available to anyone who is interested in pregnancy after transplantation.

Major Contribution

This research group has made "a major contribution in terms of keeping track of as many pregnancies as they have been able to follow," said Phyllis August, MD, from Weill Cornell Medical College in New York City. "They've performed a very important service to the community," she added.

Dr. August acknowledged the association seen between cyclosporine, and to some degree tacrolimus, and more blood vessel constriction leading to higher blood pressure, and the fact that babies were born a bit earlier in the cyclosporine and tacrolimus groups than in the azathioprine group. "But for the most part," she told Medscape Medical News, the drugs "are pretty safe to use in pregnancy."

She explained that even with these complications, most nephrologists would not consider switching a patient to azathioprine. "We believe that cyclosporine and tacrolimus are better drugs to prevent rejection and for the long-term health of the kidney," she said.

However, because mycophenolate is contraindicated in pregnancy, if another drug is needed to prevent kidney rejection, the choice is azathioprine with or without prednisone.

 
It's definitely one of the miracles of transplantation.
 

When asked if the time between transplantation and pregnancy matters, Dr. August echoed Dr. Constantinescu, and said that what is most important is the way the kidney is functioning; you want "a good kidney with a good creatinine — as close to 1 mg/dL as possible — and normal blood pressure."

Under ideal circumstances — meaning a well-matched living donor kidney — Dr. August said her advice is that women wait 1 year after transplantation before becoming pregnant. After that, "go for it. It's definitely one of the miracles of transplantation that reproductive function is restored almost to normal and that women can have babies."

In less than ideal circumstances — a deceased donor kidney and a somewhat elevated creatinine level — she said she would advise women to wait 2 years, "just to let the kidney declare itself." For women with creatinine levels in the area of 2 mg/dL, "you have to have a serious talk with your nephrologist," she advised.

Pregnancy itself is a strain on the kidney, and the role that hemodynamic, immunologic, and inflammatory factors play is not clear, Dr. August explained.

She said she would like to see more rigorous studies on the children's immune systems as they develop, but said that several of her patients have children in college, and they seem to be fine.

The national registry is supported by grants from Astellas Pharma US, Pfizer, and BMS. Ms Coscia, Dr. Constantinescu, and Dr. August have disclosed no relevant financial relationships.

Kidney Week 2014: American Society of Nephrology Annual Meeting. Abstracts TH-PO1120 and TH-PO1052. Presented November 13, 2014.

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