Pregnancy and Dialysis

A woman with no past medical history was admitted to the ICU service with acute kidney injury secondary to atypical HUS. She was early in pregnancy and we were consulted in order to start dialysis. The management of a pregnant dialysis patient is no simple matter.

About 13-36% of TTP-HUS in women is associated with pregnancy. Pregnancy may be a risk factor for developing TTP-HUS because of hypercoagulability, loss of integral endothelial cell membrane proteins, decreased fibrinolytic activity and ADAMTS13 activity. Among all patients with pregnancy associated TTP-HUS, 8% occurs in the 1^st trimester, 16% in the 2^nd trimester and 77% in the 3^rd trimester or post-partum. 

There are a number of factors to think about in the management of pregnant dialysis patients:

1. Duration and frequency of dialysis:  Pregnant patient usually start on daily dialysis with a predialysis BUN goal of <50mg/dl. It has been shown that patients on nocturnal hemodialysis with an average of 48hours/week have better outcomes than women who dialyzed 20 to 26 hours/week.

2. Anemia:  Pregnant women usually require higher doses of erythropoietin and iron, with goal of Hg>10g/dl, and transferrin saturation>30%. These targets are based more on patients in the general dialysis population and are not evidence based. Pregnant women are usually anemic although their red cell mass increases.

3. Hypophosphatemia: Our daily phosphorous ingestion is 800 to 1600mg. 2.5g to 3.0g phosphorous is removed during a regular 4 hour dialysis treatment. Phosphorous levels will decrease in patients who receive intensive hemodialysis.   Hypophosphatemia can cause tissue hypoxia and intracellular depletion of adenosine triphosphate with impairment of glucose metabolism. In a pregnant patient, our goal is to keep the phosphorous level >3mg/dl with either po repletion or supplemental phosphorous in the dialysate.

4. Calcium: 25 to 30 g of calcium is required for fetal skeletal growth. This demand requires transfer of 140mg/kg/day calcium across the placenta. To prevent osteopenia, it is recommended that an additional 1500mg of calcium be ingested daily during pregnancy.

In conclusion, adequate dialyses, treatment of anemia, maintenance of nutrition and electrolyte stability are the most important factors for a successful pregnancy in chronic dialysis patients. The outcomes of pregnancy in dialysis patients were reviewed in a previous blog post.

 

Our patient was started on 6 times/week hemodialysis for 4 hours each session.  Her phosphorous level was 2-2.5mg/dl after 1 week on hemodialysis.  With aggressive oral repletion and a regular diet, her phosphorous level was maintained at 3mg/dl upon discharge. 

Posted by Jie Cui

Azathioprine in pregnancy

We recently discussed this issue in conference and I thought it might be worth sharing a few interesting points:

Azathioprine is normally converted to the active metabolite 6-mercaptopurine. However, in pregnancy the placenta can metabolize azathioprine to thiouric acid, an inactive metabolite. In addition the fetal liver does not have inosinatopyrophosphorylase which therefore largely protects the fetus from exposure to active compounds.

Azathioprine has been classed as FDA category D - positive evidence of risk.
Despite conflicting data, general expert opinion suggests that azathioprine may be considered for use during pregnancy in certain situations (where the potential benefits outweigh potential risks).

In terms of breast feeding, in a small study, active metabolites have been detected in small quantities in breast milk. Overall the significance of this remains to be fully determined. Manufacturers have taken the official stance to warn against breast feeding while taking the drug.


As with all considerations of alterations in immunosuppressive dosing, careful consideration of risks and benefits should be explored in detail with the treating physician before any change is undertaken.