In-depth Review
Pregnancy in chronic renal insufficiency and end-stage renal disease

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Abstract

Childbearing is important to women with renal disease, but pregnancy has generally been regarded as very high risk in these women. In this review, an attempt is made to clarify the nature and severity of those risks in the settings of chronic renal insufficiency and end-stage renal disease, including dialysis patients and transplant recipients. Hypertension is the most common life-threatening problem in all three groups. A wide range of antihypertensive medications have been used, with angiotensin-converting enzyme inhibitors the only drugs absolutely contraindicated because of their association with neonatal anuria, pulmonary hypoplasia, and neonatal death. Women with serum creatinine levels of 1.4 mg/dL or greater are at risk for accelerated loss of renal function compared with women who don't become pregnant. Transplant recipients have a risk for loss of renal function similar to controls as long as renal function is well preserved. The frequency of conception is decreased in women with renal insufficiency and markedly decreased in dialysis patients (0.5% per year). Return of fertility is the rule in transplant recipients. Exposure to immunosuppressive drugs, including prednisone, azathioprine, cyclosporine, and tacrolimus, has not been associated with an increase in congenital anomalies. These drugs, particularly cyclosporine, have been associated with small-for-gestational-age babies. Transplant recipients are at risk for infections that have implications for the fetus, including cytomegalovirus, herpes simplex, and toxoplasmosis. All groups have an increased risk for prematurity and intrauterine growth restriction. The percentage of pregnancies resulting in surviving infants in women with renal insufficiency and transplant recipients ranges from 70% to 100%. For women who conceive after starting dialysis, the likelihood of a surviving infant is approximately 50%.

Section snippets

Chronic renal insufficiency

The most compelling problem that distinguishes women with renal insufficiency from other women with renal disease who conceive is the loss of renal function. Although hypertension and increased proteinuria are common in all women with renal disease who conceive, there appears to be a critical degree of renal insufficiency that puts a woman who becomes pregnant at risk for an accelerated decline in renal function. This observation is long standing, but systematic evidence to support it has been

Pregnancy in dialysis patients

Fertility is markedly reduced in dialysis patients. Estimates of the frequency of conception in dialysis patients ranges from 1.4% per year in Saudi Arabia16 to 0.5% in the United States.15 Both these estimates are based on surveys that covered only half the women of childbearing age treated with dialysis. A report from Belgium, based on a survey to which all the dialysis units in the country responded, put the frequency at 0.3% per year.17 There is a widespread impression that conception in

Pregnancy in transplant recipients

Fertility is usually restored in women with renal transplants, and pregnancy is common, occurring in 12% of the women of childbearing age in one series.24 The recovery of fertility is less common in women who undergo transplantation close to the end of their childbearing years.

Preconception counseling

Women of childbearing age being considered for renal transplantation who are not rubella immune should receive the rubella vaccine before transplantation because live virus vaccines are contraindicated posttransplantation (Table 2).

. Monitoring and Management of the Pregnant Transplant Recipient

Pretransplantation
   Rubella vaccine
Criteria for advising pregnancy
   2 years posttransplantation
   Stable renal function with creatinine ≤2.0 mg/dL
   BP ≤140/90 mm Hg on medications
   Proteinuria <500 mg

Infections

Both dialysis patients and transplant recipients face the risk for infection during pregnancy. Women transplant recipients are at increased risk for bacterial infections during pregnancy. Forty percent have urinary tract infections, and these women should have monthly screening urine cultures.35 If asymptomatic bacteriuria is present, the patient should be treated for 2 weeks and may be treated with suppressive doses of antibiotics for the rest of the pregnancy. At the time of delivery,

Worsening renal function in the pregnant transplant recipient

The differential diagnosis and initial workup of worsening renal function in the pregnant transplant recipient are listed in Table 3.

. Worsening Renal Function in the Pregnant Transplant Recipient

Differential DiagnosisInitial Workup
PreeclampsiaBlood pressure
Cyclosporine toxicityCyclosporine level
Acute rejectionRenal ultrasound
Chronic rejectionUrine culture
Recurrent disease24-Hour urine protein
Hemolytic uremic syndromeLDH, transaminases, uric acid
PyelonephritisCBC
ObstructionPlatelet count,

Anemia

The hematocrit decreases almost invariably in hemodialysis patients who conceive. Transplant recipients and women with renal insufficiency may also have a decrease in hematocrit greater than that seen in normal pregnancy. The reason for anemia is not clear, but it appears to be more complicated than simple iron deficiency.

Choice of modality

When the first cases of pregnancy in peritoneal dialysis patients were reported, it appeared that the outcome was better for peritoneal dialysis patients than for hemodialysis patients.78 With the accumulation of more data, it has become clear that the apparent superiority of peritoneal dialysis simply reflected the overall improvement in outcome for pregnancies in dialysis patients compared with earlier reports.15

There are theoretical advantages to peritoneal dialysis in that there are no

Calcium and phosphorus

Thirty grams of calcium are necessary for calcification of the fetal skeleton. If the patient is dialyzed on a bath containing more than 3.5 mEq/L of calcium, dialysis easily provides this amount. If she is dialyzed on a lower calcium bath, enough calcium should be absorbed from phosphate binders if she takes at least 2 g of calcium daily. 1,25 Dihydroxyvitamin D preparations, either oral or intravenous, are usually continued, although their effect in pregnancy is not well understood. The

Nutritional considerations

Providing a dietary prescription for the pregnant dialysis patient requires extrapolation from the usual diet prescribed for healthy pregnant women and that prescribed for a nonpregnant dialysis patient.82 Tentative guidelines are listed in Table 4.

. Nutritional Guidelines for Pregnant Dialysis Patients

Calories
   HD35 kcal/kg/d + 300 kcal
   PD25 kcal/kg + 300 kcal
Protein
   HD1.2 g/kg ideal pregravid weight + 10 g
   PD1.4 g/kg ideal pregravid weight + 10 g + dialysate losses
Vitamins
   ANo

Obstetric management

Care of the pregnant dialysis patient and transplant recipient requires close cooperation between the nephrologist and a high-risk pregnancy specialist experienced in treating women with renal disease. A neonatologist should be prepared for the care of a newborn of a mother with renal disease.

Management issues in the newborn

Infants born to both dialysis patients and transplant recipients should be observed in a high-risk setting even if they appear healthy. Infants of dialysis patients are born with blood urea nitrogen and creatinine levels equal to the mother's, and they generally experience an osmotic diuresis after birth. Without careful monitoring and replacement, they develop volume contraction and electrolyte abnormalities.84

Calcium should be monitored carefully because infants exposed to hypercalcemia are

Conclusion

Pregnancy in the transplant recipient can be anticipated and planned for. Under the appropriate circumstances, physicians may encourage it and the desire for parenthood may even influence the decision to undergo transplantation. Although one might have anticipated severe problems for the fetus exposed to immunosuppressive drugs, the problems encountered to date are manageable and do not compare with the risk to the fetus of renal failure.

For women with chronic renal insufficiency and for

References (84)

  • JL Holley et al.

    Gynecologic and reproductive issues in women on dialysis

    Am J Kidney Dis

    (1997)
  • SH Hou et al.

    Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or continuous ambulatory peritoneal dialysis

    Am J Kidney Dis

    (1985)
  • SN Sturgiss et al.

    Effect of pregnancy on long-term function of renal allografts

    Am J Kidney Dis

    (1992)
  • JM Davison

    The effect of pregnancy on kidney function in renal allograft recipients

    Kidney Int

    (1985)
  • IZ Beitins et al.

    The transplacental passage of prednisone and prednisolone in pregnancy near term

    J Pediatr

    (1972)
  • I Penn et al.

    Parenthood following renal transplantation

    Kidney Int

    (1980)
  • S Saarikoski et al.

    Immunosuppression during pregnancy. Transmission of azathioprine and its metabolites from mother to fetus

    Am J Obstet Gynecol

    (1973)
  • JM Davison

    Pregnancy in renal allograft recipients: Prognosis and management

    Clin Obstet Gynaecol (Bailliére's)

    (1994)
  • Y Ville et al.

    Pregnancy in liver transplant recipients: Course and outcome in 19 cases

    Am J Obstet Gynecol

    (1993)
  • BM Sibai et al.

    Effects of diuretics on plasma volume in pregnancies with long-term hypertension

    Am J Obstet Gynecol

    (1984)
  • GW Gladstone et al.

    Propranolol administration during pregnancy: Effects on the fetus

    Pediatrics

    (1975)
  • SC Pruyn et al.

    Long-term propranolol therapy in pregnancy: Maternal and fetal outcome

    Am J Obstet Gynecol

    (1979)
  • MKW Cottle et al.

    Maternal and fetal cardiovascular indices during fetal hypoxia due to cord compression in chronically cannulated sheep

    Am J Obstet Gynecol

    (1983)
  • J Cockburn et al.

    Final report of study on hypertension during pregnancy: The effects of specific treatment on growth and development of the children

    Lancet

    (1982)
  • GD Waisman et al.

    Magnesium plus nifedipine: Potentiation of hypotensive effect in preeclampsia?

    Am J Obstet Gynecol

    (1988)
  • IE Bhorat et al.

    Malignant ventricular arrhythmias in eclampsia: A comparison of labetolol with dihydralazine

    Am J Obstet Gynecol

    (1993)
  • MF Gadallah et al.

    Pregnancy in patients on chronic ambulatory peritoneal dialysis

    Am J Kidney Dis

    (1992)
  • TJ Evans et al.

    Congenital cytomegalovirus infection after maternal renal transplantation

    Lancet

    (1975)
  • VT Armenti et al.

    Medical management of the pregnant transplant recipient

    Adv Ren Replacement Ther

    (1998)
  • ZJ Hagay et al.

    Congenital cytomegalovirus infection: A long-standing problem still seeking a solution

    Am J Obstet Gynecol

    (1996)
  • C Hutto et al.

    Intrauterine herpes simplex virus infections

    J Pediatr

    (1987)
  • BM Sibai et al.

    Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome)

    Am J Obstet Gynecol

    (1993)
  • SH Hou et al.

    Pregnancy in women with end-stage renal disease: Treatment of anemia and premature labor

    Am J Kidney Dis

    (1993)
  • S Hou et al.

    Management of the pregnant dialysis patient

    Adv Ren Replacement Ther

    (1998)
  • J Brookhyser et al.

    Medical nutrition therapy in pregnancy and kidney disease

    Adv Ren Replacement Ther

    (1998)
  • MJ Hussey et al.

    Obstetric care for renal allograft recipients or for women treated with hemodialysis or peritoneal dialysis during pregnancy

    Adv Ren Replacement Ther

    (1998)
  • DL Blowey et al.

    Neonatal outcome in pregnancies associated with renal replacement therapy

    Adv Ren Replacement Ther

    (1998)
  • E Imbasciatti et al.

    Pregnancy in women with chronic renal failure

    Am J Nephrol

    (1986)
  • S Abe

    Pregnancy in glomerulonephritic patients with decreased renal function

    Hypertens Pregnancy

    (1996)
  • P Jungers et al.

    Pregnancy in women with impaired renal function

    Clin Nephrol

    (1997)
  • DC Jones et al.

    Outcome of pregnancy in women with moderate or severe renal insufficiency

    N Engl J Med

    (1996)
  • R Kimmerle et al.

    Pregnancies in women with diabetic nephropathy: Long-term outcome for mother and child

    Diabetologia

    (1995)
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    Received January 30, 1998; accepted in revised form July 24, 1998.

    Address reprint requests to Susan Hou, MD, Section of Nephrology, Rush Presbyterian St Luke's Medical Center, 1653 West Congress Pkwy, Chicago, IL 60612. E-mail: [email protected]

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