Chronic renal disease, once an absolute contraindication to pregnancy, is now encountered much more often as the prognosis has become much better in the past 30 years. Currently, the best prognostic indicator is the degree of renal disease (mild moderate or severe) present before pregnancy.
For mild disease (creatinine <1.5 mg/dL), the majority of women do well and their pregnancies progress without difficulty. With moderate renal disease (creatinine 1.5–3 mg/dL), fetal outcome is usually good (>90%), but maternal status often deteriorates (up to 40% of these women). With severe disease (creatinine >3 mg/dL), women are usually infertile, and if pregnancy is achieved, the outcome for both the fetus and the patient are poor.
The normal physiologic changes seen in pregnancy are different in women with chronic renal disease. Glomerular filtration rate does increase, but often only in the patients with mild disease. Proteinuria usually more than doubles in women with underlying renal disease. Interestingly, though, even nephrotic range proteinuria is not considered by itself to be harmful to the patient or the fetus.
Despite all of the preceding generalizations, it is difficult to counsel women based on their serum creatinine alone. This is due to the fact that specific renal diseases tend to behave differently from one another. Therefore, it is important to know the patient's underlying condition before managing her during pregnancy. Also, the presence of hypertension before conception, regardless of the patient's renal function and serum creatinine, increases the risk to both mother and fetus. One generalization that can be made, though, is that women with chronic renal disease are at increased risk of developing gestational hypertension and preeclampsia. Therefore, all of these women should be watched closely for these diseases.
It should be stated that most of the data regarding chronic renal disease and pregnancy are based on retrospective and observational data only.
Chronic renal disease can be staged based on the patient's glomerular filtration rate (Table 28–2). Women with chronic renal disease may also demonstrate some degree of elevation in serum creatinine.
Table 28–2. Stages of Chronic Renal Disease. ||Download (.pdf)
Table 28–2. Stages of Chronic Renal Disease.
|Stage||Description||GFR (mL/min/1.73 m2)|
|1||Kidney damage with normal or increased GFR||≥90|
|2||Kidney damage with mildly decreased GFR||60–89|
|3||Moderately decreased GFR||30–59|
|4||Severely decreased GFR||15–29|
|5||Kidney failure||<15 or dialysis|
Chronic renal disease is associated with an increased risk of a number of obstetrical complications, including preeclampsia, prematurity, intrauterine growth restriction, and pregnancy loss. The risk of these complications increases with increasing maternal serum creatinine level.
General guidelines for management of patients with chronic renal disease begins with preconceptual counseling, if possible. Pregnancy should be discouraged for patients with a serum creatinine above 1.5 (some would allow up to 2.0, especially if the patient is normotensive), or at least the patient should be made fully aware that the pregnancy may have a very poor outcome for her fetus and herself. In fact, approximately 40% of women with this level of chronic kidney disease may experience an irreversible decline in glomerular filtration rate that is greater than predicted based on the patient's previous course. Patients with more than minimal disease should be comanaged by a maternal–fetal medicine specialist and either a nephrologist or an internist familiar with the management of renal diseases. Blood pressure should be strictly controlled. Baseline laboratory values should include serum creatinine, electrolytes, albumin, and cholesterol/triglycerides (for nephritic patients), and some would add baseline liver function tests, uric acid, and lactate dehydrogenase levels to help aid in the subsequent diagnosis of superimposed preeclampsia. A 24-hour urine collection for protein and creatinine clearance should be obtained as well. Patients should have close follow-up and start noninvasive fetal monitoring at approximately 32 weeks. Baby acetylsalicylic acid and calcium therapy for the prevention of preeclampsia may be considered in these patients to start after 10 weeks' gestation.
Acute glomerulonephritis during pregnancy is rare, with an estimated incidence of 1 in 40,000 pregnancies. The condition is associated with increased perinatal loss. The clinical course is variable during pregnancy and may be easily mistaken for preeclampsia. In some patients, the condition resolves early in pregnancy, with return to normal renal function. Microscopic hematuria with RBC casts is a common finding in acute glomerulonephritis. Treatment is similar to that of the nonpregnant patient and consists of controlling blood pressure, preventing congestive heart failure, administering fluids and electrolytes, and close follow-up.
The outcome of pregnancy with chronic glomerulonephritis depends on the degree of functional impairment of the kidneys, blood pressure levels before conception, and the exact histology of the glomerulonephritis. For patients with active glomerulonephritis, the principal risk for pregnancy is superimposed preeclampsia. Conditions associated with poor fetal outcome include preexisting hypertension, severe proteinuria during the first trimester, primary focal and segmental hyalinosis, and sclerosis. Successful pregnancy should be anticipated, although renal function is expected to decrease. The incidence of fetal intrauterine growth restriction, premature labor, abruptio placentae, and intrauterine fetal demise is increased. Routine prenatal care should include periodic renal function tests, control of blood pressure, ultrasonic evaluation of fetal growth, and antepartum testing for fetal well-being. Hypertension at the time of conception correlates with worsening maternal renal function during pregnancy. Early delivery is indicated after evaluation of pulmonary maturity as appropriate.
It is unclear whether patients with SLE are more likely to have a flare during pregnancy. It is known that an exacerbation is more likely if the patient has active disease at conception. Therefore, many people recommend delaying pregnancy until the SLE has been in remission for 6–12 months. This can decrease the risk of flare from 66% to 33%. What seems to be true is that pregnancy itself does not cause the flare. In small controlled studies, the rate of flare is not different between SLE-similar pregnant and nonpregnant women. If a flare does occur, severe renal manifestations can occur. Prednisone and other immunosuppressive agents have been used with success during pregnancy.
SLE patients, like other renal patients, also have a worse prognosis if pregestational hypertension exists. Specific to SLE, however, is the poor prognosis associated with antiphospholipid antibodies and lupus anticoagulant.
Systemic Sclerosis and Periarteritis Nodosum
For patients with these diseases, the outcome for the patients and their pregnancies is quite poor. Most of the (scant) literature describes poor fetal outcome, accelerating maternal hypertension, and occasional maternal death. There are some new data showing a better prognosis with angiotensin-converting enzyme (ACE) inhibitor treatment, but at this time most authorities recommend against conception and for early termination, if possible.
Diabetic nephropathy refers to diabetic patients with proteinuria of 300 mg/d. It is most commonly seen in pregestational type 1 diabetic patients, but as the pregnant population ages, more women with type 2 diabetes will have diabetic nephropathy by the time they become pregnant.
Currently, perinatal survival in these patients is approximately 95%, compared with 99% in the general population. Pregnancy does not seem to worsen renal function in mildly affected patients at baseline (serum creatinine <1.5, creatinine clearance >80 mL/min), but for those patients with moderate or severe renal dysfunction at baseline, they typically worsen as pregnancy progresses. It is unclear whether pregnancy worsens these patients' long-term renal function. Some studies suggest that for women with severe renal dysfunction, those who become pregnant progress to renal failure sooner than those who do not become pregnant.
Some of the renal deterioration can be avoided by strict blood pressure control during pregnancy. Because ACE inhibitors are generally contraindicated in pregnancy, a calcium channel blocker can be used instead to control hypertension, as they also have renal protective properties.
Reflex nephropathy is a disease of the urinary tract system that starts in childhood. It is a common and generally mild disease. The majority of women have preserved renal function and are normotensive; consequently, their pregnancies are uneventful. The only significant complication that does develop is bacteruria and urinary tract infections. Therefore, they should be frequently screened for bacteruria and treated accordingly. In addition to this, because the disease may be inherited, their children should be evaluated after birth for this condition.
Polycystic Kidney Disease
Although the recessive form is quite rare and extremely severe, autosomal dominant polycystic kidney disease is more common and has been studied in pregnancy. Like other renal diseases, these patients do well in pregnancy if they start without hypertension and severe renal dysfunction. Again, like with the other diseases, they are more likely to develop gestational hypertension and preeclampsia. These patients, however, are also more prone to develop urinary tract infections.
A solitary kidney may be the result of developmental aberration or disease requiring removal of 1 kidney. A single kidney may be abnormally developed or it may be located low, perhaps even within the true pelvis. A second small, virtually functionless kidney may not be discovered by the usual diagnostic tests. Anatomic and functional hypertrophy of the kidney usually occurs and is augmented by pregnancy. These patients should be evaluated preconceptually for the presence of infection. If renal function is normal, pregnancy is not contraindicated, and good outcomes are expected.
During pregnancy, infection in a solitary kidney must be treated aggressively. An increased rate of preeclampsia with a solitary kidney has been reported.
Approximately 0.5% of women who have undergone transplantation in the reproductive age range become pregnant. A number of large series document successful pregnancy outcomes after renal transplantation. Patients with adequate renal function before pregnancy will experience little if any deterioration in graft function during pregnancy. The likelihood of graft rejection during pregnancy remains the same as in nonpregnant graft recipients. For renal transplant patients considering pregnancy, a stable serum creatinine level <1.4 mg/dL identifies a group more likely to experience an uncomplicated obstetric outcome (97% vs. 75% for patients with a higher serum creatinine level). The spontaneous abortion rate is not increased.
Patients should wait 2 years from transplantation to attempt pregnancy. They may wait only 1 year if the kidney is from a living-related donor. This is done to avoid rejection. Despite this recommendation, women who do not wait this period are still likely to have a successful pregnancy. Patients should have a serum creatinine of <2 (and preferably <1.5) as well as no signs of rejection before conception. Patients should not be hypertensive or should be made normotensive with medication before conception.
Antirejection drugs should be reduced to maintenance levels (prednisone ≤15 mg/d and azathioprine ≤2mg/kg/d; a safe dosage for cyclosporine has not been established but should be maintained <5 mg/kg/d if possible). Immunosuppressive levels should be checked frequently, as levels tend to decrease in pregnancy. Patients on steroids should have early glucose intolerance screening. Electrolyte and liver function values should be checked every 6 weeks.
The risk of infection is considerably higher during pregnancy in renal transplant patients. Primary or reactivated herpesvirus or cytomegalovirus infection may be seen. A higher rate of hepatitis B surface antigenemia is seen in dialysis patients as well.
The route of delivery depends primarily on obstetric indications. In patients with aseptic necrosis of the hip joints or other bony dystrophy secondary to long-standing disease, caesarean delivery may be required. Vaginal delivery should be the aim for patients with renal transplant. A transplanted kidney in the false pelvis usually does not cause obstruction leading to dystocia. If a caesarean section becomes indicated, close attention should be made not to damage the transplanted kidney, as it is typically located in the pelvis.
Preterm delivery, both spontaneous and indicated, is common (45–60%). Intrauterine growth restriction and fetal abnormalities caused by immunosuppressive agents taken by the mother may occur.
Chronic Renal Disease Requiring Dialysis
As opposed to the horrendous pregnancy outcome noted in older literature, there are data that women on dialysis have approximately a 50% chance of delivering a live infant, albeit often growth restricted or premature. There are a number of pregnancy-related differences in dialysis management:
- Erythropoietin requirements are higher to maintain an appropriate hemoglobin concentration.
- Fetal heart and uterine contraction monitoring are required, as dialysis may induce hypotension or placental insufficiency.
- The placenta produces vitamin D, so the dose of calciferol may need to be reduced to avoid hypercalcemia.
- Since pregnancy is a hypercoagulable state, more heparin may be required during dialysis.
For mild disease (serum creatinine <1.5 mg/dL), the majority of women do well, and their pregnancies progress without difficulty. With moderate renal disease (creatinine 1.5–3 mg/dL), fetal outcome is usually good (>90%), but maternal status often deteriorates (up to 40% of these women). With severe disease (creatinine >3 mg/dL), women are usually infertile, and if pregnancy is achieved, the outcome for both the fetus and the patient are poor.
Armenti VT, Radomski JS, Moritz MJ, et al. Report from the National Transplantation Pregnancy Registry (NTPR): Outcomes of pregnancy after transplantation. In: Cecka JM, Terasaki PI (eds): Clinical Transplants.
Los Angeles, CA: UCLA Immunogenetics Center; 2002, p. 97.
Bar J, Ben-Rafael Z, Padoa A, Orvieto R, Boner G, Hod M. Prediction of pregnancy outcome in subgroups of women with renal disease. Clin Nephrol
Cohen RA, Brown RS. Microscopic hematuria. N Engl J Med
Lindheimer MD, Davison JM, Katz AL. The kidney and hypertension in pregnancy: Twenty exciting years. Semin Nephrol