Chapter 28. Renal & Urinary Tract Disorders in Pregnancy

For a discussion of normal renal and urinary tract function in pregnancy, see Chapter 6, Normal Pregnancy.

Asymptomatic Bacteriuria

Essentials of Diagnosis

• Urine culture demonstrating the presence of bacteria in the urine in the absence of maternal symptoms of urinary tract infection

Pathogenesis

Asymptomatic bacteriuria is defined as the presence of actively multiplying bacteria in the urinary tract, excluding the distal urethra, in a patient without any obvious symptoms. The incidence is the same in nonpregnant and pregnant females and averages 2–10%; however, a number of physiologic changes that occur during pregnancy predispose a woman to bacteriuria, including increased glucose concentration in the urine and increased stasis due to the relaxant progesterone effect. Risk factors for developing asymptomatic bacteriuria include low socioeconomic status, parity, age, sexual practice, and medical conditions such as diabetes and sickle cell trait. Escherichia coli is the most common offending organism for asymptomatic bacteriuria (approximately 80% of cases). The Klebsiella-Enterobacter-Serratia group, Staphylococcus aureus,Enterococcus, group B Streptococcus, and Proteus are responsible for the remainder of cases.

The primary concern with asymptomatic bacteriuria in pregnancy is that it is associated with an increased risk of both maternal and fetal complications during pregnancy (see later).

Prevention

Certain underlying medical disorders may predispose a woman to asymptomatic bacteriuria during pregnancy. Asymptomatic bacteriuria is twice as common in pregnant women with sickle cell trait and 3 times as common in pregnant women with diabetes or with renal transplant as in normal pregnant women. Therefore, we advise that monthly routine urine cultures should be performed in these women when pregnant.

Clinical Findings

The diagnosis of asymptomatic bacteriuria is based on isolation of microorganisms with a colony count >105 organisms per milliliter of urine in a clean-catch specimen in a woman who is experiencing no symptoms of urinary tract infection. When obtaining a clean-catch specimen, the patient should be instructed to clean the vulvar area from front to back to avoid contamination of the urine sample.

Complications

The main risk of asymptomatic bacteriuria is the development of pyelonephritis. Due to anatomic dilation in the renal system during pregnancy, there is increased stasis of urine in the pregnant urinary tract and a much higher risk of developing an overt infection from the bacteruria. Due to this risk, many authorities advocate screening all pregnant women for bacteruria, and unlike nonpregnant women, a pregnant woman found to have bacteruria should be treated promptly. If asymptomatic bacteriuria is left untreated in pregnancy, up to 40% of patients will develop symptoms of urinary tract infection (UTI), a significant increase from the almost negligible risk in nonpregnant women. Approximately 25–30% of women will develop acute pyelonephritis. With treatment, the rate is less than 10%. Asymptomatic bacteriuria has been associated with preterm delivery, fetal loss, and preeclampsia. Treatment of asymptomatic bacteruria has been associated in large reviews with a reduction in the risk of preterm birth and low birth weight babies. On the other hand, approximately 2% percent of pregnant women with a negative urine culture will develop symptomatic cystitis and pyelonephritis.

Treatment

A midstream urine specimen should be collected for culture at the initial prenatal visit and repeated later in pregnancy. At each prenatal visit, dipstick testing should be performed. If proteinuria is present, urinalysis, culture, or both should be done. A pregnant woman with sickle cell trait should have urine culture and sensitivity testing every 4 weeks. The US Preventive Health Task Force states that single urine culture at 12–16 weeks' gestation has 80% sensitivity. Alternatively, regular dipstick testing for leukocyte esterase and nitrites has a negative predictive value >95% and sensitivity of 50–92%.

Pregnant women should be encouraged to maintain adequate fluid intake and to void frequently.

The initial antibiotic selection should be empiric. Based on the fact that the most common offending pathogen is E coli, a sulfonamide, nitrofurantoin, or a cephalosporin is a reasonable choice. These antibiotics should be safe for the mother and fetus, with minimal side effects. A 5- to 14-day course of one of these agents will effectively eradicate asymptomatic bacteriuria in approximately 65% of pregnant patients. A urine culture should be repeated 1–2 weeks after therapy is started. Recurrent infections occur in approximately 30% of patients treated once and in approximately 15% of patients who have been treated twice and/or have not responded to initial therapy.

Nitrofurantoin (US Food and Drug Administration [FDA] category B) should be avoided in mothers with glucose-6-phosphatase deficiency. Additionally, sulfa drugs (FDA category B) are often avoided late in pregnancy because of the theoretical increased likelihood of neonatal hyperbilirubinemia. Tetracyclines (FDA category D) are contraindicated during pregnancy because of dental staining in the exposed child. Trimethoprim (FDA category C) is a folic acid antagonist; therefore, trimethoprim-sulfamethoxazole is generally avoided during organogenesis; it may be used when alternatives are limited.

Suppressive therapy may be appropriate for women with bacteriuria that persists after 2 or more courses of therapy. Nitrofurantoin (50–100 mg orally at bedtime) for the duration of the pregnancy is a commonly used.

Acute Cystitis

Essentials of Diagnosis

• Urine culture demonstrating the presence of bacteria in the urine in a patient symptomatic for urinary tract infection

Pathogenesis

Acute cystitis is uncommon in pregnancy (approximately 1%). The bacteria causing acute cystitis are similar to those in asymptomatic bacteriuria.

Clinical Findings

Clinically, the patient presents with symptoms of urinary frequency, urgency, dysuria, and suprapubic discomfort. The urine often is cloudy and malodorous and should be cultured to confirm the diagnosis and to identify antibiotic sensitivities. A colony count of ≥103 confirms cystitis in a symptomatic patient.

Treatment

The treatment of cystitis is the same as for asymptomatic bacteriuria. A urine culture should be repeated 1–2 weeks after therapy is started. As with asymptomatic bacteriuria, suppressive therapy may be appropriate for women with UTI that persists after 2 or more courses of therapy. Nitrofurantoin (50–100 mg orally at bedtime) for the duration of the pregnancy is commonly used.

Acute Pyelonephritis

Essentials of Diagnosis

• The presence of bacteria in urine culture
• Maternal symptoms of flank pain and/or systemic signs of fever, chills, nausea/vomiting

Pathogenesis

Acute pyelonephritis occurs in 1–2% of all pregnant women (usually, although not invariably, in those with previous asymptomatic bacteriuria) and is associated with risk to the mother and fetus. It is one of the most common causes of hospitalization during pregnancy.

Certain anatomic changes that occur during pregnancy predispose pregnant women to pyelonephritis, including increased stasis of the urine in the urinary tract due to smooth muscle relaxation in the ureters.

Prevention

Acute pyelonephritis is best prevented by screening for and treating asymptomatic bacteruria.

Clinical Findings

Clinical manifestations of acute pyelonephritis include fever, shaking chills, costovertebral angle tenderness, flank pain, nausea and vomiting, headache, increased urinary frequency, and dysuria. Patients almost always have pyuria on urinalysis. Urine examination will reveal significant bacteriuria with pyuria and white blood cell casts in the urinary sediment. A count of 1–2 bacteria per high-power field in unspun urine or >20 bacteria in the sediment of a centrifuged specimen of urine collected by bladder catheterization helps in the bedside diagnosis. The absence of pyuria should raise suspicion for another disorder. Due to this, a urine specimen should be obtained and sent for culture before any antibiotics are given in order to properly identify the causative organism and antibiotic susceptibility. Blood cultures may also be sent, as they will be positive 10–20% of the time, although it is unclear whether management should be any different for women with positive blood cultures as outcomes tend to be the same.

Differential Diagnosis

For the patient presenting with back or flank pain, the differential diagnosis includes appendicitis, musculoskeletal pain, costochondritis, and chorioamnionitis. Urinalysis and urine culture can help to differentiate among these disorders.

Complications

Maternal complications include fever, bacterial endotoxemia, endotoxic shock, renal insufficiency, anemia, leukocytosis, thrombocytopenia, and elevated fibrin split product levels. Risk factors for recurrent or severe disease are a history of pyelonephritis, urinary tract malformation, or urinary calculi. The maternal anemia may be due to marrow suppression, increased erythrocyte destruction, or diminished red cell production. Pulmonary dysfunction has been described in association with acute pyelonephritis. Symptoms and signs may range from minimal (mild cough and slight pulmonary infiltrate) to severe (adult respiratory distress syndrome requiring intensive therapy).

Obstetrical complications include preterm labor and prematurity, fetal death, and intrauterine growth restriction.

Treatment

A pregnant woman with pyelonephritis initially should be evaluated in the hospital. Antibiotics should be given parenterally once a urine culture is sent, and hypovolemia should be corrected. Acetaminophen can be used as an antipyretic, if indicated. Vital signs, including respiratory rate, and input and output should be closely monitored. Pulse oximetry may be useful. A first-generation cephalosporin (FDA category B) such as cefazolin 1 g parenterally every 8 hours usually is effective. However, due to increasing antibiotic resistance, the local susceptibilities should be considered when selecting the initial antibiotic. Ceftriaxone 1 g parenterally every 24 hours often is effective for most Enterobacteriaceae in this setting. The urine culture and sensitivities guide therapy thereafter. When the patient is afebrile for 48 hours, parenteral therapy may be changed to an effective oral antibiotic. A total course of 14 days of antibiotic is commonly administered. Note that drugs with very high protein binding, such as ceftriaxone, may be inappropriate the day before parturition because of the possibility of bilirubin displacement and subsequent kernicterus.

If no clinical response is seen in 48–72 hours, a resistant organism can be treated by adding an aminoglycoside such as gentamicin 3–5 mg/kg per 24 hours in 3 divided doses given every 8 hours. Failure to respond may be caused by urolithiasis or a structural urinary tract abnormality. Ultrasound imaging of the kidneys and urinary tract usually is the next diagnostic test if the patient does not defervesce after 48 hours of antibiotic therapy. Perinephric abscess causing persistent pain and fever can be identified by ultrasound. Perinephric abscess usually is due to obstruction complicated by infection. The perinephric abscess should have percutaneous drainage (preferably computed tomography or ultrasound-guided) for both diagnostic and therapeutic purposes, in addition to administration of antibiotic therapy. An intravenous pyelogram or computed tomography urogram is often useful if a lack of response continues. A preliminary “scout” film and a film taken 15 minutes after administration of intravenous contrast often are helpful. In selected cases of persistent infection or obstruction, cystoscopy and retrograde pyelography are needed.

Although many women who present with pyelonephritis will have uterine contractions, they are almost always due to the fever and resultant hypovolemia. Tocolytics should be used with extreme caution, as they can greatly increase the risk of respiratory distress. Typically the contractions resolve with the administration of intravenous (IV) fluids and antibiotics.

Respiratory distress is a severe systemic complication of pyelonephritis. It is caused by bacterial endotoxins increasing alveolar permeability and a resultant pulmonary edema. It is more common in women with the following: tachycardia, tachypnea, blood transfusion, fever of 103° degrees, tocolytics, and excessive IV fluids. Patients presenting with respiratory symptoms should be managed aggressively and often require an intensive care setting, as shock can ensue.

Prognosis

Cunningham reported that after an episode of pyelonephritis, recurrent bacteriuria occurred in 28% of women, and pyelonephritis recurred in 10% during the same pregnancy. A more recent study by Wing et al identified that 5% of pregnant patients had urine culture positive for organisms only 2 weeks after completion of initial therapy for pyelonephritis. In the same study, 6.3% had culture positive for organisms later in their antepartum course, and 6.3% developed recurrent pyelonephritis. For this reason, antibiotic suppressive therapy with nitrofurantoin 100 mg orally at bedtime, or a similar regimen, is continued during the pregnancy and during the puerperium, often for 6 weeks (Table 28–1). Monthly urine cultures to identify a recurrent UTI may be similar in effectiveness to antibiotic suppression for patients who are allergic or who prefer not to take antibiotics.

Periodic culture of the urine assists in detection of recurrence. Relapse is defined as recurrent infection from the same species and type-specific strain of organism present before treatment; this represents a treatment failure. Most relapses occur <2 weeks after completion of therapy. Reinfection is recurrent infection due to a different strain of bacteria after successful treatment of the initial infection, occurring >3 weeks after the completion of therapy.

Essentials of Diagnosis

• Maternal symptoms of urinary tract obstruction that may include back or flank pain, hematuria, and/or dysuria
• Evidence of urinary tract calculi on imaging studies

Pathogenesis

The incidence of urinary calculi is not altered by pregnancy. The incidence is 0.03–0.35% of pregnancies, and the incidence increases as gestational age advances (only 20% present in the first trimester). Stones cause obstruction, infection, pain, and hematuria (present in 75–95% of patients, one-third of whom have gross hematuria). Recurrent hospitalization, preterm labor and delivery, and need for operative intervention are increased. The causes of urinary calculi are the same in pregnant and nonpregnant women: chronic UTI, hyperparathyroidism or other causes of hypercalciuria, gout (uric acid), and obstructive uropathy. Congenital or familial cystinuria and oxaluria are less common causes. Most stones are composed of calcium, usually calcium phosphate.

The physiologic hydroureter of pregnancy is more prominent on the right side; however, stones occur with equal frequency on either side. The physiologic hydroureter of pregnancy increase the likelihood that a pregnant patient will spontaneously pass her stone(s).

Clinical Findings

Patients may present with a variety of symptoms, including typical renal or ureteric colic, vague abdominal or back pain that may radiate into the groin, fever, nausea, and vomiting. The patient may have a history of recurrent UTI or hematuria. Fever, bacteriuria, and flank pain may suggest coexisting pyelonephritis from obstruction. The differential diagnosis includes other acute abdominal conditions unrelated to pregnancy (eg, appendicitis, biliary colic or tract disease, adnexal torsion) and conditions related to pregnancy (eg, abruption placentae, preterm labor, chorioamnionitis). When fever attributed to pyelonephritis persists beyond 48 hours of parenteral antibiotic treatment, then obstruction due to urolithiasis must be evaluated. Hematuria, ranging from microscopic to gross, is usually present, although it is not pathognomonic for urolithiasis. The index of suspicion should be high in the clinical situations described, in patients in whom urine culture is negative in the setting of suspected pyelonephritis, or in cases of persistent hematuria or recurrent UTI.

Clinical diagnosis is confirmed by ultrasound examination of the urinary tract. In a study by Butler et al in 57 pregnant women had 73 admissions for symptomatic nephrolithiasis over a 13-year period, they noted that calculi were visualized in 21 of 35 (60%) renal ultrasonographic examinations and 4 of 7 (57%) abdominal x-ray studies when these were performed as the initial test. In contrast, urolithiasis was discovered in 93% of cases (n = 8) in which single-shot intravenous pyelography was performed as the initial diagnostic test. In selected cases, excretory urography includes a precontrast scout film and another image obtained 20 minutes after contrast injection. This examination exposes the fetus to 0.2 rad. The common indications for intravenous pyelography include microscopic hematuria and recurrent UTI. Sterile urine culture should be performed when pyelonephritis is suspected. Alternate means of assessing for urinary tract stones during pregnancy if ultrasound is inconclusive include magnetic resonance urography (which involves no radiation exposure to the fetus) and computed tomography urogram.

Differential Diagnosis

The differential diagnosis of urinary tract calculi includes pyelonephritis, appendicitis, chorioamnionitis, cholecystitis, and cholelithiasis. The combination of urinalysis, urine culture, and imaging studies of the abdomen and pelvis can distinguish among these diagnoses.

Complications

A recent retrospective cohort study by Swartz et al found that women admitted for nephrolithiasis during pregnancy had an increased risk of preterm delivery versus those without stones (adjusted odds ratio = 1.8; 95% confidence interval, 1.5–2.1). This finding has potential implications for counseling of pregnant women with kidney stones requiring hospital admission and possible use of biomarkers (eg, cervical length or fetal fibronectin testing) to better identify at-risk pregnancies. Additionally, it may prompt definitive treatment of small, asymptomatic stones in women during reproductive years.

Treatment

Treatment includes hospital admission, adequate hydration, urine culture and Gram stain, appropriate antibiotic therapy, correction of electrolyte imbalances, and systemic analgesia (eg, opioids). Epidural analgesia may be considered for patients with severe pain. Most (75–85%) stones pass spontaneously, due in part to the normally dilated urinary tract of pregnancy. The patient should strain her urine so that a stone can be analyzed. Surgical intervention, such as ureteral stenting, transurethral cystoscopic stone extraction, nephrostomy drainage, or open surgery, can be performed by a urologist if indicated for unremitting pain, sepsis, infection unresponsive to antibiotic therapy, or obstructive uropathy. Shock wave lithotripsy is contraindicated during pregnancy, although it has been performed in 6 pregnancies inadvertently. More recently, ureteroscopy and holmium:YAG laser lithotripsy has been performed successfully in 8 pregnant women with 10 symptomatic stones and 2 encrusted ureteral stents. This device delivers energy to a localized area, can be used with flexible ureteroscopes, and is effective with stones of all compositions. Procedural success was achieved in all but 1 case (91%), with no obstetric or urologic complications.

Essentials of Diagnosis

• Acute renal failure is defined as sudden reduction in renal function and glomerular filtration rate.
• The most common causes of acute renal failure in pregnancy are severe preeclampsia and placental abruption.

Pathogenesis

Acute renal failure is defined as sudden impairment in kidney function that leads to retention of waste products (eg, urea) and abnormal fluid and electrolyte balance. It occurs infrequently in pregnancy but carries a high mortality rate; therefore, it must be prevented when possible and treated aggressively. Most cases in pregnancy result from acute hypovolemia associated with obstetric hemorrhage (placenta previa, placental abruption, or postpartum hemorrhage), preeclampsia, or sepsis.

Clinically, acute renal failure is a condition in which the kidneys are temporarily unable to perform their excretory and regulatory functions. Blood urea nitrogen and serum creatinine concentrations are increased. Without prompt intervention, the condition may result in abortion, low birthweight, premature labor, and stillbirth. Dialysis may be required. Although hypotension-induced preterm contractions may occur during dialysis, numerous successful pregnancy outcomes have been reported after dialysis during pregnancy. In these cases renal failure most often is the result of intrinsic renal disease.

Similar to nonpregnant patients, acute renal failure can be classified as prerenal, renal, or postrenal. A classic formula in determining the cause of renal failure is the fractional excretion of sodium (FENa). It is defined as the (urine sodium/plasma sodium) divided by (urine creatinine/plasma creatinine). It can also be stated as (urine sodium × plasma creatinine) divided by (urine creatinine × the plasma sodium). Either way, it reflects the amount of sodium excreted as compared with the creatinine. If the renal tubules are working (eg, as in prerenal failure) the sodium excretion should be less than the creatinine, as the kidneys work extra hard to maintain sodium. If the tubules are not working (eg, renal cause, acute tubular necrosis), the kidneys will not be able to resorb sodium and the fractional sodium excreted will be elevated. This can also be measured with urinary sodium levels.

In the prerenal type, acute renal failure occurs due to renal hypoperfusion secondary to maternal hypovolemia (eg, hemorrhage, hyperemesis gravidarum, dehydration, abruptio placentae, septicemia), circulating nephrotoxins (eg, aminoglycosides), aortic or renal artery stenosis or a narrowed off renal arteriole (due to sepsis, nonsteroidal anti-inflammatory drugs [NSAIDs], and certain dyes), mismatched blood transfusion, preeclampsia–eclampsia, disseminated intravascular coagulation, and hypoxemia (eg, chronic lung disease and heart failure). In prerenal failure, the patient typically is clinically hypovolemic with an increased pulse and decreased blood pressure. Laboratory tests show a serum blood urea nitrogen (BUN) to creatinine ratio >20, an FENa <1, urinary sodium <20 mEq/L (often <10) and urinalysis with concentrated urine, few elements in sediment, and positive hyaline casts.

Renal causes can be divided into 4 groups: glomerular, tubular, interstitial and vascular. For all groups, the FENa is >1. Glomerular causes can be from systemic lupus erythematosus (SLE), postinfectious glomerulonephritis, or membranoproliferative glomerulonephritis. In the preceding causes, low complement levels are found. With normal complement levels, the glomerular causes can be immunoglobulin A nephropathy, Goodpasture's syndrome, or rapidly progressive glomerulonephritis. In all glomerular causes, urinalysis shows red blood cell (RBC) casts, dysmorphic RBC's and protein.

When the renal failure is from the tubules, it is called acute tubular necrosis. It can be caused by an ischemic insult, shock, and surgery. It can also be caused by toxins, either endogenous (magnesium, creatinine phosphokinase) or exogenous (drugs, dyes, aminoglycosides). These patients typically have a normal physical exam. Urinalysis may be normal or may have brown pigmented casts. Urinary sodium is >25 mEq/L (often >60). Again, FENa is >1.

Renal failure from the interstitium can be caused by NSAIDs and allergies (often to penicillins and cephalosporins). Eosinophils are found in the blood and urine. The patients typically have a fever and rash. If renal failure is caused by a vasculitis, “telescoped” urinary sediment may be seen, in which red cells, white cells, oval fat bodies, and all types of casts are noted in relatively equal amounts.

The postrenal type is caused by urinary obstruction from ureteric stone, retroperitoneal tumor, and other diseases. Bilateral ureteral obstruction due to polyhydramnios is rare. The BUN to creatinine ratio is usually approximately 10.

Prevention

In obstetric practice, prevention of acute renal failure should be the aim, with appropriate volume replacement to maintain adequate urine output. Proper management of high-risk obstetric conditions (eg, preeclampsia–eclampsia, abruptio placentae, chorioamnionitis), ready blood availability, and avoidance of nephrotoxic antibiotics are important.

Clinical Findings

Acute renal failure is defined as urine output <400 mL in 24 hours (or <0.5 mL/kg/h) or an increase in serum creatinine (at least 1.5 fold). BUN concentrations are also typically increased.

The clinical course has been divided into an oliguric phase, a diuretic phase, and a recovery phase. In the oliguric phase, urine output drops to <30 mL/h, with accumulation of BUN and potassium. The patient becomes acidotic with the increase in hydrogen ion and loss of bicarbonate. In the diuretic phase, large volumes of dilute urine are passed, with loss of electrolytes due to absence of function of the renal tubules. As tubular function returns to normal in the recovery phase, the volume and composition of urine normalize. Clinical manifestations and complications include anorexia, nausea and vomiting, lethargy, cardiac arrhythmia (secondary to electrolyte disturbance), anemia, renal or extrarenal infection, thrombocytopenia, metabolic acidosis, and electrolyte imbalance (hyperkalemia, hyponatremia, hypermagnesemia, hyperphosphatemia, hypocalcemia).

Complications

Without prompt intervention, obstetric complications include pregnancy loss, low birth weight, premature labor, and stillbirth.

Treatment

Specific treatments include the following.

Emergency Treatment

Underlying causes of acute renal failure (eg, hemorrhagic shock) may require emergency treatment for correction of the underlying disorder.

Surgical Measures

Surgical measures include determination and correction of any obstructive uropathy or sepsis due to infected products of conception. Such problems should be treated as surgically appropriate. If obstructive uropathy is determined to be the cause, the placement of a ureteral stent or nephrostomy is indicated. Infected products of conception can be removed via dilation and curettage. Hypovolemia due to internal bleeding or uterine bleeding may require laparotomy to ligate any bleeding blood vessels or hysterectomy for definitive treatment of uterine bleeding.

Routine Measures

Routine measures include achieving fluid and electrolyte balance. Fluid intake can be calculated from urinary output, loss of fluid from other sources (eg, diarrhea, vomiting), and insensible loss of approximately 500 mL/d (correcting for fever may be necessary). Intake and output must be recorded carefully. The patient should be weighed daily and should maintain a constant weight or lose weight slowly (250 g/d assuming a room temperature of 22–23 °C [71–73 °F]). Hyperkalemia is a significant problem that can be controlled by administering glucose and insulin. The diet should be high in calories and carbohydrates, and low in protein and electrolytes. Parenteral feeding may be given in cases of nausea and vomiting. Prophylactic antibiotics should not be used, but known infections can be treated with antibiotics without renal toxicity. Indwelling bladder catheters are to be avoided when possible.

Dialysis

Dialysis is indicated if serum potassium levels rise to 7 mEq/L or more, serum sodium levels are 130 mEq/L or less, the serum bicarbonate is 13 mEq/L or less, BUN levels are more than 120 mg/dL or there are daily increments of 30 mg/dL in patients with sepsis, and dialyzable poisons or toxins are present. Different criteria are applied for renal failure in the antepartum period with a continuing pregnancy. In these cases, dialysis is instituted earlier in the process in consideration of fetal well-being. Although specific criteria have not been firmly established, one commonly used figure is a BUN level of 60 mg/dL.

Special Circumstances: Thrombotic Thrombocytopenic Purpura–Hemolytic Uremic Syndrome

Thrombotic thrombocytopenic purpura–hemolytic uremic syndrome (TTP-HUS) is characterized by the otherwise unexplained combination of thrombocytopenia and microangiopathic anemia. Renal failure caused by thrombotic microangiopathy may occur. Patients have been traditionally considered to have TTP when neurologic abnormalities are dominant and acute renal failure is minimal or not present, and considered to have HUS when acute renal failure is dominant and neurologic abnormalities are minimal or absent. Renal insufficiency may occur in either pregnancy-associated TTP or HUS, although it is more prevalent among patients with HUS. The optimal therapy of TTP-HUS developing in association with pregnancy includes delivery because distinction from preeclampsia may not be possible but is otherwise the same as for patients who are not pregnant. Patients who were treated with plasma infusion with or without plasma exchange in a series resulted in improved survival.

Essentials in Diagnosis

• Chronic renal disease is defined as persistent kidney damage with impairment in renal function.
• The prognosis for pregnancy outcome depends on the degree of renal impairment.

Pathogenesis

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.

Clinical Findings

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.

Complications

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.

Treatment

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.

Glomerulonephritis

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.

Lupus Nephritis

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

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.

Reflux Nephropathy

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.

Solitary Kidney

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.

Renal Transplantation

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.

Prognosis

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.