Pregnancy and Kidney Transplantation: Frequently Asked Questions

During my nephrology fellowship, I was asked by a renal transplant recipient at her 9-month post transplant clinic visit “Doctor, can I become pregnant?  Will I have a live healthy baby? Will my kidney function get affected?” I did not have clear answers then and read extensively on the subject.

**below, I will summarize what I have learned about pregnancy in kidney transplantation, please consult your nephrologist before you consider pregnancy if you have a kidney transplant**

The first successful pregnancy in kidney transplant recipient occurred in 1958 to the 23 year old Edith Helm who had received a kidney from her identical twin sister Wanda Foster. Thus, this occurred not long after the first kidney transplant in 1954. She delivered a healthy full term boy of 3300 grams by cesarean section 2 years after her transplant. Interestingly, even her donor and twin sister Wanda Foster gave birth four times successfully after kidney donation.

Chronic kidney disease is associated with disruption of hypothalamic gonadal axis primarily causing hyperprolactinemia and anovulation due to absence of the luteinizing hormone surge.

Pregnancy is rare in women with ESRD with the incidence of conception ranging from 0.9 to 7%. Kidney transplantation is associated with normalization of the reproductive hormones and restoration of fertility as soon as 6 months after transplantation and gives us an apparent large window of opportunity to help women of childbearing age who want to have babies. On the other hand, deteriorating allograft function may narrow this window unpredictably. In addition, pregnancy in kidney transplant recipients is challenging due to the side effects of immunosuppressive medications, and higher risk of adverse maternal and fetal complications. Therefore, It becomes important as physicians to counsel and medically optimize kidney transplant recipients who wish to become pregnant.

I have put below common questions that are frequently asked by women with history of kidney transplant.

Question: Is pregnancy possible after a kidney transplant?

Answer: Yes, pregnancy is possible in kidney transplant recipients. However, there are several important things that one must consider before you decide to conceive like timing of conception, risk and changes in immunosuppression that we have discussed below. It is extremely important that you talk to your transplant nephrologist about this beforehand.

Question: What is the likelihood of maternal complications if I do decide to get pregnant?

Answer: There is a 6 fold higher likelihood of preeclampsia in women who have a kidney transplant and a reported incidence of 15-25%. There is a also 5 fold higher risk of needing a cesarean section. However, there is no increased risk of maternal mortality.

Question: Will I have a live healthy baby?

Answer: Likely Yes, having had a kidney transplant does not increase fetal mortality, especially if the timing is right and adequate precautions are taken (see below). However there is a 12 fold high likelihood of preterm and low birth weight babies; and a 3 fold higher likelihood of having small for gestational age babies.

Question: What are the risk factors associated with poor maternal and fetal outcomes?

Answer: The two most important risk factors are serum creatinine > 1.4 mg/dl, presence of hypertension during pregnancy and proteinuria > 500 mg/24h. It is advisable to become pregnant sooner than later - younger age at conception is associated with better outcome.

Question: What is the optimal time to conceive?

Answer: The optimal time to conceive is after 6 months and within 2 years of getting the transplant. It is known that if time to conception is more than 2 years of getting a transplant, it reduced the likelihood of viable fetal outcomes.

Question: Will pregnancy affect my allograft function?

Answer: Likely No, the kidney allograft is able to adapt normally to physiological changes of hyperfiltration in pregnancy. An uncomplicated pregnancy does not increase the risk of kidney loss. However it may affect graft function if you have risk factors like higher pre-pregnancy creatinine (or lower kidney function) or develop hypertension during pregnancy.

Question: What are the changes in immunosuppression that are made if I wish to become pregnant?

Answer: Mycophenolic acid (cellcept) and sirolimus are teratogenic, and must be stopped 6 weeks prior to conception. Cellcept has shown to be associated with limb and facial anomalies tacrolimus/cyclosporine (class C), azathioprine (class D) and low dose maintenance prednisone (< 20 mg/day) (class B)  are safe to be used during pregnancy. Even though azathioprine is listed as class D, it is to safe to be used during pregnancy because the fetal liver lacks the enzyme inosinate pyrophosphorylase that converts it to active metabolite 6 mercaptopurine; and fetus is protected from its adverse effect.

Question: My friend wants to donate a kidney. Will donating a kidney affect her future pregnancy?

Answer: Likely No, donating a kidney does not affect the chances of her becoming pregnant. Post-donation, however, there is a 2.5 fold higher risk of preeclampsia and gestational hypertension in living donors, without any associated fetal complications.

Question: I am currently on dialysis. Should I try to become pregnant now or wait till I get a kidney transplant?

Answer: The incidence of conception on dialysis patients is very low ranging from 1-7%. Even when women with ESRD are able to conceive, the incidence of live birth is 20-40%. Women should be advised to wait till they get a transplant. However if the wait list for transplant is long due to high PRA or they are getting older, they may be advised to try to conceive while on dialysis. How Intensification of dialysis to >36 hours per week is associated with improved fetal outcomes with a live birth rate of 85%.

For a review of Pregnancy in Kidney Transplant review its entry in NephMadness ‘15.

Post by Silvi Shah, NSMC Intern

Hyperammonemia - When should we start dialysis?

I would like to discuss a case that I recently saw in renal consult. He was a man in his 60s with history of end stage liver disease who received a liver transplant. His hospital course was complicated by anuric ATN and liver graft failure. As a result, he was started on dialysis on post-operative day 0.  Dialysis was stopped on post-op day 2 due to recovering renal function. On post-op day 3 he became encephalopathic. His ammonia level was elevated to 337 and did not improve with conventional therapy with lactulose/rifaximin. The question was whether to start dialysis or not in spite of his recovering renal function.

Causes: The urea cycle in the liver in which ammonia gets converted to urea is responsible for excretion of waste nitrogen.  Hyperammonemia in newborns is most commonly associated with inherited disorders of amino acid and organic acid metabolism. Causes in adults include Reye’s syndrome, liver failure, sepsis especially infections with urea splitting organisms, high dose chemotherapy, drugs (salicyclates, valproate), gastrointestinal bleeding, multiple myeloma, parenteral nutrition and late onset of urea cycle defects. The latter usually presents with episodic encephalopathy precipitated by metabolic stressors like infection, anesthesia or pregnancy.

Clinical features: Hyperammonemia can be life threatening and if persistent can lead to irreversible neuronal damage. It leads to cerebral edema causing progressive encephalopathy. Respiratory alkalosis is common due to central hyperventilation. Severe hyperammonemia can also cause seizures. An MRI brain is usually consistent with hypoxic ischemic encephalopathy

When to start dialysis? There are no published guidelines for when to initiate dialysis in a patient with hyperammonemia due to urea cycle defects. It is commonly indicated if the ammonia blood level is greater than three to four times the upper limit of normal or greater than 200 micromoles/L. Continuous hemodialysis is started with higher flow rates and is the most effective treatment in rapidly reducing ammonia levels.  Even though ammonia is osmotically active, the rapid removal of ammonia is not associated with disequilibrium syndrome mainly due to two reasons: First, there is a rapid equilibration of ammonia across the cell membrane. Secondly, the total amount in the blood, even in severe hyperammonemia, is only about 200 micromoles. This contributes less than 1 mosm per liter to total osmolality and therefore, even if it were all removed at once, the change in osmolality is too small to make cause disequilibrium. Contrast this with ammonia levels in the urine which are typically in the millimolar range.

The question remains whether to start dialysis in the setting of acute severe hyperammonemia (levels > 200 micromoles/L) and encephalopathy in adults with liver failure and normal kidney function. I was not able to find any literature on it and would like to know what the practice in other institutions is?  I believe since severe hyperammonemia can lead to irreversible brain damage, dialysis should be instituted. See this previous post concerning hyperammonemia in individuals with myeloma.

Posted by Silvi Shah