NephMadness 2015: Obstetric Nephrology Region

Joel Topf, MD; Matthew Sparks, MD; Phyllis August, MD, MPH


March 02, 2015

Editorial Collaboration

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In This Article

Pregnancy in ESRD vs Pregnancy in Kidney Transplant

Pregnancy in ESRD

Pregnancy in dialysis-dependent kidney failure leads to significant maternal and fetal morbidity and mortality. As a result, most experts advise women who want children to wait until a successful transplant, but when the biologic clock is ticking and the PRA is high and the wait for a transplant can be years. As such, pregnancy while on dialysis may actually be the best option. And sometimes it just happens.

The first hurdle with pregnancy in dialysis is fertility. Menstrual irregularities typically begin with a GFR of 15 mL/min and amenorrhea occurs at a GFR of 5 mL/min. Even when menstruation is maintained, ovulation can be absent due to loss of the LH surge.

In a registry of female dialysis patients of childbearing age from the '90s, the fertility rate was 2.4% for HD and 1.1% for PD over 4 years (0.5% per year for the entire registry). There is data that shows that fertility improves with higher doses of dialysis. Also, registries and case series include women who get pregnant before starting dialysis and then required dialysis later in the pregnancy.

The earliest outcomes reported for pregnancies while on dialysis tended to be poor with only ~23% resulting in a live baby, with a mean gestational age of 32 weeks. But in 1998 Okundaye at al reported a trend toward better fetal survival in women who received more than 20 hours of dialysis a week.

Three series have been published with all of the pregnancies occurring after 2000, and they have reported live delivery rates from 86% to 100% and dialysis hours from 20-48 hours per week (Eroğlu et alHaase et al, Barua et al). In the two series that reported 100% live births, both employed intensive dialysis, either hemodiafiltration for 28 hours a week or nocturnal hemodialysis 48 hours a week. More impressive is that, in neither of those series did the women have significant residual renal function.

Anemia is a difficult problem in pregnancy given reports of increased EPO and iron requirements in pregnancy. Additionally estimating dry weight can be a challenge. Usually there is little weight gain in the first trimester followed by up to a pound per week during the second and third trimester. Physicians should target weight gain of 25 to 35 pounds. Frequent reevaluation of dry weight is needed and extra care should be taken to avoid hypotension.

Another issue that can complicate pregnancy is fetal polyhydramnios (or excessive amniotic fluid). Polyhydramnios is postulated to be the result of fetal solute diuresis secondary to a high urea concentration. This was corrected by increased dialysis time and has not been reported in contemporary series with intensive hemodialysis.

Pregnancy in dialysis is rare, but increasingly possible with good outcomes. The most generalizable lesson from pregnancy and dialysis is that a formerly hopeless situation has been completely transformed by a radical rethinking of what the appropriate dose of dialysis should be. Might pregnancy be a lantern shining a the way to think about dialysis dose in general?

Pregnancy in Kidney Transplant

Fertility usually returns to ESRD patients within ~3-4 months after a kidney transplant. However, menopause typically occurs 4-5 years earlier in patients with ESRD than in the general population, so this should be considered if there is a delay in the return of fertility. Pregnancy is fairly common after kidney transplantation. Despite a number of registries to track pregnancy after kidney transplant a minority of pregnancies are actually tracked. This means there is, almost certainly, a significant reporting bias in these registries that needs to be kept in mind when looking at the data.

Guidelines suggest delaying pregnancy until after the peritransplantation period as this is the time patients are exposed to the most fetotoxic and teratogenic anti-rejection medications. Previously, guidelines have suggested delaying pregnancy at least 2 years. However, given the increasing age of transplant patients these guidelines are being replaced with more realistic guidelines. Look for a stable creatinine less than 1.5 mg/dL with less than 500 mg/24 hours of proteinuria and of course no fetotoxic infections (CMV, etc) or fetotoxic/teratogenic medications prior to pregnancy.

Current recommendations advise against mycophenolate mofetil (MMF) and rapamycin for 6 weeks before pregnancy. Though some recommend using higher doses of calcineurin inhibitors, most recommend doctors maintain pre-transplant drug levels. Frequent monitoring may be required due to changes in eGFR and plasma volume with pregnancy. Transplant rejection can be difficult to detect clinically but kidney biopsy is generally considered safe during pregnancy, as is methylprednisolone to treat rejection. The gravid liver may be more prone to azathioprine toxicity, so regular assessment of liver enzymes is recommended. Tacrolimus pharmacokinetics can be altered during pregnancy and dose adjustments could be required.

The National Transplant Pregnancy Registry reports that about a third of post-transplant pregnancies are complicated by preeclampsia, possibly related to calcineurin inhibitor effects. Most registries report a high risk of preterm birth and low birth weight, on the order of 50-60%, and usually it is due to maternal or fetal compromise, rather than spontaneous labor.

Patients with functional kidney transplants have been conceiving and delivering babies for ~50 years. They represent a high-risk population and care must be taken for the fetus, mother, and graft but good outcomes are still likely and it is probably the best road through ESRD to motherhood.

Dr. August is the Ralph A. Baer, MD Professor of Research in Medicine, and a Professor of Medicine, Public Health, and Medicine in Obstetrics and Gynecology at Weill Cornell Medical College. She is Director of the NYP-Weill Cornell Hypertension Center, and the Program Director for the Nephrology Fellowship training program. Dr August is an expert in the field of hypertension and nephrology, Dr. August is committed to the prevention and treatment of high blood pressure. Her clinical practice at Weill Cornell is largely devoted to prevention and treatment of hypertension, kidney disease, and cardiovascular disease. She has served on numerous government advisory boards providing guidelines for the treatment of hypertension and hypertension in pregnancy. She is currently an Associate Editor for JASN.


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