Nancy A. Melville

November 08, 2013

ATLANTA — Women who have undergone kidney transplantation who discontinue mycophenolic acid immunosuppressives (MPA) before conception have more successful pregnancies, without any increase in organ rejection or graft loss, a new study shows.

"Kidney transplant recipients with stable transplant function on MPA prior to pregnancy who conceive after discontinuing treatment in the recommended timeframe, have a significantly higher rate of live births without any increase in rejection, graft loss, or birth defects," said lead investigator Vincent Armenti, MD, from the University of Central Florida College of Medicine in Orlando.

The link between MPA products and birth defects has been well documented. In fact, the US Food and Drug Administration changed the classification of the drugs to category D, indicating positive evidence of fetal risk.

To evaluate the effects on mother and child if MPA products are discontinued prior to conception, Dr. Armenti and his team from the National Transplantation Pregnancy Registry identified 114 kidney transplant recipients who conceived while taking MPA and 163 who conceived after discontinuing MPA.

The results were presented here at Kidney Week 2013.

Of those who discontinued, 69% switched to other immunosuppressive agents, most commonly azathioprine, Dr. Armenti told Medscape Medical News.

More pregnancies in the MPA group than in the discontinuation group were unplanned (19% vs 62%; P < .001).

You can safely go off the drug or switch to another drug, and the likelihood is low that you will have an organ rejection.

The rate of live births was significantly higher in the discontinuation group than in the MPA group (79% vs 43%; < .001), and the rate of miscarriage was lower (19% vs 52%; P < .001).

"These results confirm that exposure to MPA within 6 weeks of conception and during pregnancy results in significantly higher rates of spontaneous abortion and birth defects," Dr. Armenti noted.

There were no significant differences between the 2 groups in terms of kidney problems, such as graft loss within 2 years of delivery and biopsy-proven rejection during pregnancy.

The interval between transplantation and conception was significantly longer in the discontinuation group than in the MPA group. In addition, creatinine levels were lower before, during, and after pregnancy in the discontinuation group.

Dr. Armenti pointed out that the National Transplantation Pregnancy Registry is conducting more research to better understand the long-term effects of MPA on pregnancy. "Whether these recipients resume MPA postpartum, and their long-term transplant function, requires further investigation."

All recipients and transplant professionals are encouraged to report pregnancies to the registry, he said.

Nephrologist Michelle Josephson, MD, from the University of Chicago, said she agrees that more research is needed to gain a better understanding of long-term outcomes, but that this study, nevertheless, offers important insights.

"What's interesting is that this study, in a sense, is looking at 2 populations. The bottom line is that the group that conceived while still on MPA is probably a much different group for various reasons," she told Medscape Medical News.

"Whether they neglected to tell their physician that they planned to conceive or the physician failed to inform them of the risks associated with conceiving while on MPA isn't known, but there are a number of clues that say the group that conceived while on MPA is not doing quite as well on several levels," Dr. Josephson said.

"There are more unplanned pregnancies, it looks like they got pregnant a little sooner after transplant, and kidney function prior, during, and after pregnancy is not as good," she pointed out.

The finding that there were no differences in graft loss or organ rejection is also significant, Dr. Josephson said. "I think it's important for reassuring people that you can safely go off the drug or switch to another drug and the likelihood is low that you will have an organ rejection."

But, she added, "another important lesson here is that patients who have the planned pregnancies are the ones who, overall, seem to do better, but maybe that's not much of a surprise."

This study was funded by Novartis, Astellas, Pfizer, and Bristol-Myers Squibb. Coauthor Michael Moritz, MD, reports being a consultant for Highmark Blue Shield and receiving research funding from Novartis and Bristol-Myers-Squibb. Dr. Josephson has disclosed no relevant financial relationships.

Kidney Week 2013: the American Society of Nephrology 46th Annual Meeting. Abstract SA-PO1017. Presented November 9, 2013.


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