COMMENTARY

Management of the Pregnant Dialysis Patient

Case Presentation

An outside nephrologist calls you to arrange transfer of dialysis care for a 31 year old woman who has been on dialysis for 3 months and has become pregnant. She is 16 weeks pregnant by ultrasound. The high risk OB visit is essentially unremarkable. The patient is on dialysis 3 times each week, M-W-F via a left arterio-venous fistula. Time on dialysis (Qt) is 3.5 hours, on an F8 dialyzer. Her recent monthly labs show a BUN of 72 mg/dL, creatinine of 8.1 mg/dL, K 4.6 mEq/L, calcium and phosphorus 9.8 and 5.2 mg/dL, respectively. Her Hgb is 11.6 g/dL, WCC 6.0x10⁹/L, plats 192,000. Her urea reduction ratio (URR) is 68%, KT/V of 1.24.  Her beta HCG level is highly positive. What are the next steps?

Discussion

Pregnancy is uncommon and usually unplanned in patients undergoing chronic hemodialysis. Only 42% of pre-menopausal women on dialysis have normal menstrual periods; most women are in fact anovulatory. Other reproductive endocrine abnormalities in female dialysis patients include hyperprolactinemia, low serum progesterone levels, and absent LH/FSH surges. The overall conception rate in dialysis patients is 0.3-1.4%/year, and the pregnancy rate is greater for patients on hemodialysis than those on peritoneal dialysis.

Claudio Luders and colleagues from São Paulo, Brazil published their experience on the management and outcomes of pregnant women on dialysis in AJKD in 2010. This is a fantastic paper because of the size of the study, the details that they provide, and the uplifting results.

In their paper, Luders et al present retrospective data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis at the São Paulo University Medical School (São Paulo, Brazil). They analyzed maternal and fetal outcomes of all of these 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as preeclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, they performed logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight.

The main findings of their study were:

87% overall rate of successful delivery, with a mean gestational age of 32.7+/- 3.1 weeks.

Preeclampsia was associated with a poor prognosis compared with pregnancies without pre eclampsia:

• a successful delivery rate of 60% versus 92.9% (P <0.02)
• extremely premature delivery rate of 77.8% versus 3.3% (P <0.001)
• lower gestational age (P <0.001), and birth weight (P <0.001).

Patients with an adverse composite fetal outcome had:

• a higher frequency of preeclampsia (P <0.001)
• lower frequency of polyhydramnios (P<0.03)
• lower third-trimester hematocrit (P< 0.03),
• higher predialysis serum urea level (P <0.03).

Luders et al in their paper explain their approach to managing the dialysis prescription. Essentially, they use a short frequent dialysis schedule that is adjusted initially for whether the patient has residual renal function and the body weight. They dialyze their patients 6 times weekly on a high-flux, high-efficiency dialyzer. For patients with a urine output >1,000 mL/day, who are less <1 year on dialysis therapy, and have a body weight <70 kg, they start off with a 1.5- to 2.0-hour dialysis treatment 6 times/weekly. In contrast, for patients with a urine output<1,000 mL/day, who are > 1 year on dialysis therapy, or have a body weight >70 kg they start initially with a 2.0- to 3.0-hour dialysis treatment 6 times weekly. They say that they individualize the dialysis prescription based on laboratory, ultrasonographic, and clinical parameters. They also indicate that for complications, such as severe hypertension, anorexia, frequent nausea or vomiting, uncontrolled edema, excessive weight gain, and persistent polyhydramnios, the dialysis time is increased by 30-minutes.

The other study that has generated considered interest is from Barua et al (2)

They describe their experience with five patients (age range, 31 to 37 yr) who had seven pregnancies while on nocturnal hemodialysis and delivered six live infants. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 ± 10 to 48 ± 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean blood pressure were maintained within normal physiological parameters. The mean gestational age of the six live births was 36.2 ± 3 wk and the mean birth weight was 2417.5 ± 657 g. The maternal and fetal complications that were observed included, intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, Barua et al augmented dialysate phosphate supplementation regimen as required.

The dialysis prescription that was used comprised of 7 nights of nocturnal for 8 hours at a blood flow and dialysate flow rate 300 to 400 ml/min and 500 to 750 ml/min, respectively. They used either a F80 polysulfone dialyzer (Fresenius Medical Care, Lexington, MA) or the Exceltra 120 dialyzer (Baxter, Chicago, IL). The dialysate composition was as follows: sodium, 137 to 140 mEq/L (mmol/L): potassium, 1.5 to 2 mEq/L (mmol/L); bicarbonate, 35 mEq/L; and calcium 6 to 7 mg/dL (1.5 to 1.75 mmol/L).

Susan Hou from Loyola University in Chicago, in an accompanying editorial (3) in AJKD discusses both papers.

She writes:

“Luders and colleagues provide several important insights. Women who start dialysis after conception need not be on a dialysis regimen of 20 or 48 h/wk. Over 75% of women who start dialysis after conception have a surviving infant, although those who have cared for even 1 woman with a late fetal loss know that 75% is not good enough. We have concentrated on outcomes in women who conceive after starting dialysis because their outcomes have been so poor. There may also be benefit to carefully measuring residual kidney function in women who conceive after starting dialysis. It is clear that the prevention of preeclampsia is urgent in women with kidney disease as it is in all areas of obstetrics”.

Regarding the Barua study, Hou writes:

These unprecedented results reinforce our views that time on dialysis is an important factor in outcomes. Our usual approach is to prescribe 4 hours of dialysis 6 d/wk in an attempt to be sure of reaching 20 h/wk even with access problems and snow days. The schedule is onerous for patients, whose motivation may fade as the pregnancy progresses. In the United States, it is difficult to offer even the most motivated pregnant woman 48 h/wk of dialysis since nocturnal dialysis programs (home or in center) are not yet widely available. The overall success rate of 87% in the current report compares favorably even to the outcomes of pregnancy in transplant recipients, although the mean gestational age of 32.7 weeks is not as good. The success rate of 79% infant survival for pregnancies in women who conceived after starting dialysis is dramatically better than the 50% we reported in 1998”.

What might be the next steps for our patient?

In the United States, where nocturnal dialysis is not easily available, one reasonable approach would be to schedule 4 hours of dialysis 6 days each week (for a total of 24 hours of dialysis) using a high flux polysulfone dialyzer. Adjusting the dialysate to achieve electrolyte concentrations in the patient that parallel the levels observed for that stage of a normal pregnancy is important; however, there is no "normal" value for pregnancy -- it changes as pregnancy progresses.

Generally, however, serum sodium is decreased approximately 5 mEq/L as compared to the non-pregnant state and plasma osmolality decreases by approximately 10 mOsm/Kg H20. Serum potassium level is not altered (although there is total body K retention overall). Pregnancy causes a respiratory alkalosis -- arterial pC02 decreases by approximately 10 mmHg and arterial pH increases slightly to 7.44. The chronic respiratory alkalosis is associated with a decrease in serum bicarbonate to 17 to 20 mEq/L.

Some general adjustments can be made: for example, modifying the HC03 bath to 25 mEq/L (for the normal HC03 in pregnancy of 17-20 mEq/L), and calibrating the dialysate sodium to achieve a serum sodium of 134 mEq/L. No adjustment in the heparin dose is necessary since heparin does not cross the placenta. Very careful monitoring of volume is key, but adjusting this as plasma volume and weight increases, and as pregnancy progresses is also important.

Peritoneal dialysis is another option, but is limited by the volume of exchanges that are tolerable (approximately 1500 cc exchanges) and the potential issues in both the mother and fetus with exposure to high glucose dialysate. Most centers prefer hemodialysis over peritoneal dialysis unless ther are specific reasons that hemodialysis is contraindicated or not preferred.

References

1. Luders C, Castro MC, Titan SM, De Castro I, Elias RM, Abensur H, Romão JE Jr. Obstetric outcome in pregnant women on long-term dialysis: a case series. Am J Kidney Dis. 2010 Jul;56(1):77-85. Epub 2010 Apr 10. PubMed PMID: 20382457.

2. Barua M, Hladunewich M, Keunen J, Pierratos A, McFarlane P, Sood M, Chan CT.Successful pregnancies on nocturnal home hemodialysis. Clin J Am Soc Nephrol. 2008 Mar;3(2):392-6. PubMed PMID: 18308997; PubMed Central PMCID: PMC2390936.

3. Hou S. Pregnancy in women treated with dialysis: lessons from a large series over 20 years. Am J Kidney Dis. 2010 Jul;56(1):5-6. PubMed PMID: 20620681.