CHAPTER 53: Renal and Urinary Tract Disorders

Renal and urinary tract disorders are frequently encountered in pregnancy. Some precede pregnancy—one example being nephrolithiasis. In some women, pregnancy-induced changes may predispose to development or worsening of urinary tract disorders—an example is the markedly increased risk for pyelonephritis, described above by Williams. Finally, some renal pathology is unique to pregnancy, such as preeclampsia. With good prenatal care, however, most women with these disorders will likely have no long-term sequelae.

Significant changes in both structure and function within the urinary tract during normal pregnancy are discussed in Chapter 4 (Urinary System). The kidneys become larger, and dilatation of the right renal calyces and ureters can be striking (Fig. 53-1). Some dilatation develops before 14 weeks and likely stems from progesterone-induced relaxation of the muscularis. More marked dilatation is apparent beginning in midpregnancy because of more distal ureteral compression, especially on the right side (Faúndes, 1998). There is also some vesicoureteral reflux during pregnancy. Because of these physiological changes, the risk of upper urinary infection rises. Also, imaging studies done to evaluate urinary tract obstruction may occasionally be erroneously interpreted.

Evidence of functional renal hypertrophy becomes apparent very soon after conception. Glomeruli are larger, although cell numbers do not grow (Strevens, 2003). Pregnancy-induced intrarenal vasodilatation develops, and both afferent and efferent resistances decline. This leads to greater effective renal plasma flow and glomerular filtration (Helal, 2012; Hussein, 2014). By 12 weeks’ gestation, the glomerular filtration rate (GFR) is already augmented 20 percent above nonpregnant values (Hladunewich, 2004). Ultimately, plasma flow and GFR rise by 40 and 65 percent, respectively. Consequently, serum concentrations of creatinine and urea drop substantively across pregnancy, and values within a nonpregnant normal range may be abnormal for pregnancy (Appendix, Serum and Blood Constituents). Other alterations include those related to maintaining normal acid-base homeostasis, osmoregulation, and fluid and electrolyte retention.

Assessment of Renal Function During Pregnancy

Urinalysis results are essentially unchanged during pregnancy, except for occasional glucosuria. Although protein excretion normally rises, it seldom reaches levels that are detected by usual screening methods. Higby and colleagues (1994) reported 24-hour protein excretion in pregnancy to be 115 mg/d with a 95-percent confidence level of 260 mg/d. Values did not significantly differ by trimester (Fig. 4-14). Albumin constitutes only a small part of total protein excretion and ranges from 5 to 30 mg/d. Airoldi and Weinstein (2007) concluded that proteinuria must exceed 300 mg/d to be considered abnormal. Many consider 500 mg/d to be important with gestational hypertension. Investigators have correlated a urinary protein-to-creatinine ratio of ≥0.3 in a spot urine sample—ideally from a first morning void—with a 24-hour protein excretion rate of ≥300 mg (Kuper, 2016).

In one study, 3 percent of 4589 nulliparas screened before 20 weeks had idiopathic hematuria, defined as 1+ or greater blood on urine dipstick (Stehman-Breen, 2002). These women had a twofold risk of developing preeclampsia. In another study of 1000 women screened during pregnancy, the incidence of dipstick hematuria was 15 percent (Brown, 2005). Most women had only trace levels of hematuria, and the false-positive rate was 40 percent.

If the serum creatinine level in pregnancy persistently exceeds 0.9 mg/dL (75 μmol/L), then intrinsic renal disease is suspected. In these cases, some determine the creatinine clearance as an estimate of the GFR. Of other assessment tools, sonography provides imaging of renal size, relative consistency, and elements of obstruction (see Fig. 53-1). Magnetic resonance (MR) imaging of renal masses provides excellent anatomic information (Putra, 2009). Full-sequence intravenous pyelography is not done routinely, but injection of contrast media with one or two abdominal radiographs may be indicated by the clinical situation. The usual clinical indications for cystoscopy are followed. Ureteroscopy is another available tool when indicated.

Although renal biopsy is relatively safely performed during pregnancy, it usually is postponed unless results may change therapy. From a review of 243 biopsies in pregnant women, the incidence of complications was 7 percent—this compares with 1 percent in postpartum women (Piccoli, 2013). Some consider biopsy for rapid deterioration of renal function with no obvious cause or for symptomatic nephrotic syndrome (Lindheimer, 2007a). We and others have found biopsy helpful in selected cases to direct management (Chen, 2001; Piccoli, 2013). In one series, renal biopsy in 12 normal pregnant volunteers showed that five had slight to moderate glomerular endotheliosis (Strevens, 2003). Recall this is the histopathological lesion that is putatively typical of preeclampsia and is characterized by fibrin deposition within the glomerular endothelium leading to capillary occlusion. In contrast, all 27 women with proteinuric hypertension had endotheliosis, and in all but one, it was moderate to severe.

Pregnancy after Unilateral Nephrectomy

In these cases, if the remaining kidney is normal, renal function becomes augmented. However, women who have donated a kidney have a higher frequency of gestational hypertension or preeclampsia in subsequent pregnancy—11 versus 5 percent compared with non-donors (Garg, 2015). Otherwise, women with one normal kidney most often have no difficulty in pregnancy. Moreover, kidney donation does not lead to long-term adverse consequences. That said, thorough functional evaluation of the remaining kidney is essential (Ibrahim, 2009).

These infections are the most frequent bacterial infections complicating pregnancy. Although asymptomatic bacteriuria is the most common, symptomatic infection includes cystitis, or it may involve the renal calyces, pelvis, and parenchyma to cause pyelonephritis. Organisms that cause urinary infections are those from the normal perineal flora. Approximately 90 percent of Escherichia coli strains that cause nonobstructive pyelonephritis have adhesins such as P- and S-fimbriae. These are cell-surface protein structures that enhance bacterial adherence and, thereby, virulence (Foxman, 2010; Hooton, 2012). Data suggest that pregnant women have more severe sequelae from urosepsis. One possible underlying factor is the T-helper cell—Th1/Th2 ratio—reversal of normal pregnancy, which is discussed in Chapter 4 (Leukocytes and Lymphocytes). Other perturbations of cytokine or of adhesin expression may be contributory (Chaemsaithong, 2013; Sledzińska, 2011). But even if pregnancy itself does not enhance these virulence factors, urinary stasis, vesicoureteral reflux, and diabetes predispose to symptomatic upper urinary infections (Czaja, 2009).

In the puerperium, several risk factors predispose to urinary infections. Bladder sensitivity to intravesical fluid tension is often diminished due to labor trauma or epidural analgesia. Bladder sensations can also be obscured by discomfort from vaginal or perineal injury. Normal postpartum diuresis may worsen bladder overdistention, and catheterization to relieve retention often leads to urinary infection. Postpartum pyelonephritis is treated in the same manner as antepartum renal infections (McDonnold, 2012).

Asymptomatic Bacteriuria

This refers to persistent, actively multiplying bacteria within the urinary tract in asymptomatic women. The incidence during pregnancy is similar to that in nonpregnant women. It varies from 2 to 7 percent, and it is characteristically population dependent. The highest incidence is in African-American multiparas with sickle-cell trait, and the lowest is in affluent white women of low parity. Asymptomatic infection is also more common in diabetics (Schneeberger, 2014).

Bacteriuria is typically present at the first antepartum visit. An initial positive urine culture result done as a part of prenatal care should prompt treatment. After this, fewer than 1 percent of women develop a urinary tract infection (Whalley, 1967). A clean-voided specimen containing more than 100,000 organisms/mL is diagnostic. It may be prudent to treat when lower concentrations are identified, because pyelonephritis develops in some women despite colony counts of only 20,000 to 50,000 organisms/mL (Lucas, 1993).

Most studies indicate that if asymptomatic bacteriuria is not treated, approximately 25 percent of infected women will develop symptomatic infection during pregnancy (Smaill, 2015). In a more recent study, only 2.4 percent of treated women developed pyelonephritis (Kazemier, 2015). Eradication of bacteriuria with antimicrobial agents prevents most of these serious infections. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (2017), as well as the U.S. Preventive Services Task Force (2008), recommend screening for bacteriuria at the first prenatal visit. Standard urine cultures may not be cost effective when the prevalence is low. Less expensive screening tests such as the leukocyte esterase/nitrite dipstick are cost effective when the prevalence is ≤2 percent (Rogozinska, 2016; Rouse, 1995). Also, a dipstick culture technique has excellent positive- and negative-predictive values (Mignini, 2009). With this, a special agar-coated dipstick is first placed into urine and then also serves as the culture plate. Because of a high prevalence—5 to 8 percent—at Parkland Hospital, most women are screened by traditional urine culture. Susceptibility determination is not necessary because initial treatment is empirical (Hooton, 2012).

In some but not all studies, covert bacteriuria has been associated with preterm or low-birthweight infants. It is even more controversial whether eradication of bacteriuria decreases these complications. Evaluating a cohort of 25,746 mother-infant pairs, Schieve and coworkers (1994) reported urinary tract infection to be associated with greater risks for low-birthweight infants, preterm delivery, pregnancy-associated hypertension, and anemia. These findings vary from those of others (Gilstrap, 1981b; Whalley, 1967). Notably, in most studies, cohorts with asymptomatic infection are not evaluated separately from those with acute renal infection (Banhidy, 2007). One Cochrane database review noted insufficient data to answer this question (Smaill, 2015).

Treatment

Bacteriuria responds to empirical treatment with any of several antimicrobial regimens listed in Table 53-1. Although selection can be based on in vitro susceptibilities, in our extensive experience, empirical oral treatment for 10 days with nitrofurantoin macrocrystals, 100 mg at bedtime, is usually effective. Satisfactory results are also achieved with a 7-day oral course of nitrofurantoin, 100 mg given twice daily (Lumbiganon, 2009). Single-dose antimicrobial therapy is less successful (Widmer, 2015). The important caveat is that, regardless of regimen given, the recurrence rate is approximately 30 percent. This may indicate covert upper tract infection and the need for longer therapy. Thus, after initial therapy, periodic surveillance is necessary to prevent recurrent urinary infections (Schneeberger, 2015).

For recurrent bacteriuria, we have had success with nitrofurantoin, 100 mg orally at bedtime for 21 days (Lucas, 1994). For women with persistent or frequent bacteriuria recurrences, suppressive therapy for the remainder of pregnancy can be given. We routinely use nitrofurantoin, 100 mg orally at bedtime. This drug may rarely cause an acute pulmonary reaction that dissipates on its withdrawal (Boggess, 1996).

Cystitis and Urethritis

Lower urinary infection during pregnancy may develop without antecedent covert bacteriuria (Harris, 1981). Cystitis produces dysuria, urgency, and frequency, but with few associated systemic findings. Pyuria and bacteriuria are usually found. Microscopic hematuria is common, and occasionally there is gross hematuria from hemorrhagic cystitis. Although cystitis is usually uncomplicated, the upper urinary tract may become involved by ascending infection. Almost 40 percent of pregnant women with acute pyelonephritis have preceding symptoms of lower tract infection (Gilstrap, 1981a).

Women with cystitis respond readily to any of several regimens. Most of the 3-day regimens listed in Table 53-1 are usually 90-percent effective (Fihn, 2003). Single-dose therapy is less effective, and if it is used, concomitant pyelonephritis must be confidently excluded.

Lower urinary tract symptoms with pyuria accompanied by a sterile urine culture may stem from urethritis caused by Chlamydia trachomatis. Mucopurulent cervicitis usually coexists, and azithromycin therapy is effective (Chap. 65, Chlamydial Infections).

Acute Pyelonephritis

Renal infection is one of the most frequent serious medical complications of pregnancy. Data from the 2006 Nationwide Inpatient Sample showed that nearly 29,000 pregnancy-associated hospitalizations were for acute pyelonephritis (Jolley, 2012). In one hospital-system database of nearly 550,000 births, its incidence was 0.5 percent (Wing, 2014). Importantly, pyelonephritis is a leading cause of septic shock during pregnancy (Snyder, 2013). In one Parkland Hospital Obstetrical Intensive Care Unit review, 12 percent of antepartum admissions were for sepsis syndrome caused by renal infections (Zeeman, 2003). Urosepsis may be related to an increased incidence of cerebral palsy in preterm infants (Jacobsson, 2002). Fortunately, affected mothers suffer no serious long-term sequelae (Raz, 2003).

Clinical Findings

Renal infection develops more frequently in the second trimester, and nulliparity and young age are risks (Hill, 2005). Pyelonephritis is unilateral and right-sided in more than half of cases, and it is bilateral in a fourth. Fever and shaking chills usually develop rather abruptly, and patients have aching pain in one or both lumbar regions. Anorexia, nausea, and vomiting may worsen dehydration. Tenderness usually can be elicited by percussion in one or both costovertebral angles. The differential diagnosis includes, among others, labor, chorioamnionitis, adnexal torsion, appendicitis, placental abruption, or infarcted leiomyoma. Evidence of the sepsis syndrome is common (Chap. 47, Sepsis Syndrome).

If this infection is suspected, a urine sample obtained by catheterization may be preferred to avoid obscuring contamination from the lower genital tract. The urinary sediment contains many leukocytes, frequently in clumps, and numerous bacteria. Bacteremia is demonstrated in 15 to 20 percent of these women. E coli is isolated from urine or blood in 70 to 80 percent of infections, Klebsiella pneumoniae in 3 to 5 percent, Enterobacter or Proteus species in 3 to 5 percent, and gram-positive organisms, including group B Streptococcus and Staphylococcus aureus, in up to 10 percent of cases (Hill, 2005; Wing, 2000).

Plasma creatinine is monitored because early studies reported that 20 percent of pregnant women developed acute kidney injury. More recent findings, however, show this to be only 5 percent if aggressive fluid resuscitation is provided (Hill, 2005). Follow-up studies have demonstrated that this endotoxin-induced damage is reversible long term. As shown in Figure 53-2, varying degrees of respiratory distress syndrome from endotoxin-induced alveolar injury are manifest in up to 2 percent of women (Cunningham, 1987; Snyder, 2013; Wing, 2014).

Uterine activity from endotoxin is common and is related to fever severity (Graham, 1993). In one study, women with pyelonephritis averaged five contractions per hour at admission, and this decreased to two per hour within 6 hours of intravenous fluid and antimicrobial administration (Millar, 2003). Notably, β-agonist therapy for tocolysis increases the likelihood of respiratory insufficiency from permeability edema (Lamont, 2000). The incidence of pulmonary edema in women with pyelonephritis who were given β-agonists was reported to be 8 percent—a fourfold increase over that expected (Towers, 1991). Endotoxin-induced hemolysis is common, and approximately a third of these women with pyelonephritis develop anemia (Cox, 1991). With recovery, hemoglobin regeneration is normal, and acute infection does not affect erythropoietin production (Cavenee, 1994).

Management

One scheme for management of acute pyelonephritis is shown in Table 53-2. Urine cultures are taken, but prospective trials show that blood cultures are of limited clinical utility (Gomi, 2015; Wing, 2000). We obtain blood cultures if the temperature is >39°C. Intravenous hydration to ensure adequate urinary output is the cornerstone of treatment. Antimicrobials are also begun promptly with the caveat that they may initially worsen endotoxemia from bacterial lysis. Surveillance for worsening sepsis syndrome includes serial monitoring of urinary output, blood pressure, pulse, temperature, and oxygen saturation. High fevers are lowered with a cooling blanket and acetaminophen. This is especially important in early pregnancy because of possible teratogenic effects from hyperthermia.

Antimicrobial therapy usually is empirical, and ampicillin plus gentamicin; cefazolin or ceftriaxone; or an extended-spectrum antibiotic are all 95-percent effective in randomized trials (Sanchez-Ramos, 1995; Wing, 1998, 2000). Fewer than half of E coli strains are sensitive to ampicillin in vitro, but cephalosporins and gentamicin generally have excellent activity. Serum creatinine levels are monitored if nephrotoxic drugs are given. Initial treatment at Parkland Hospital is ampicillin plus gentamicin. Some recommend suitable substitutes if bacterial studies show in vitro resistance. With any of the regimens discussed, response is usually prompt, and 95 percent of women are afebrile by 72 hours (Hill, 2005; Sheffield, 2005). After discharge, most recommend oral therapy for a total of 7 to 14 days (Hooton, 2012).

Persistent Infection

Generally, intravenous hydration and antimicrobial therapy are followed by stepwise defervescence of approximately 1°F per day. With persistent spiking fever or lack of clinical improvement by 48 to 72 hours, urinary tract obstruction, another complication, or both are considered. In these women, renal sonography is recommended to search for obstruction, which is manifest by abnormal ureteral or pyelocaliceal dilatation (Seidman, 1998). Although most women with continuing infection have no evidence of obstruction, some are found to have calculi. Although renal sonography will detect hydronephrosis, stones are not always seen in pregnancy (Butler, 2000; Maikranz, 1987). If stones are strongly suspected despite a nondiagnostic sonographic examination, a plain abdominal radiograph will identify nearly 90 percent. Another option is the modified one-shot intravenous pyelogram—a single radiograph obtained 30 minutes after contrast injection—which usually provides adequate imaging (Butler, 2000).

In some women, MR imaging may disclose the cause of persistent infection (Spencer, 2004). Even without urinary obstruction, persistent infection can be due to an intrarenal or perinephric abscess or phlegmon (Cox, 1988; Rafi, 2012). Obstruction relief is important, and one method is cystoscopic placement of a double-J ureteral stent (Rodriguez, 1988). Because these stents are usually left in place until after delivery, they frequently become encrusted and require replacement. We have found that percutaneous nephrostomy is preferable because the stents are more easily replaced. Finally, surgical removal of stones may be required in some women (Nephrolithiasis).

Outpatient Management

This is sometimes done for nonpregnant women with uncomplicated pyelonephritis (Hooton, 2012). Outpatient management was described in 92 pregnant women who were first given in-hospital intramuscular ceftriaxone, two 1-g doses 24 hours apart (Wing, 1999). After this, only a third of the group was considered suitable for outpatient therapy, and these women were randomly assigned either to discharge home and oral antimicrobials or to continued hospitalization with intravenous therapy. A third of the outpatient management group was unable to adhere to the treatment regimen and required readmission. This suggests that outpatient management is applicable to very few gravidas.

Recurrent urinary tract infection—either covert or symptomatic—develops in 30 to 40 percent of women following completion of pyelonephritis treatment (Cunningham, 1973). Unless other measures are taken to ensure urine sterility, nitrofurantoin, 100 mg orally at bedtime given for the remainder of the pregnancy, reduces bacteriuria recurrence (Van Dorsten, 1987).

Reflux Nephropathy

Vesicoureteral reflux in early childhood can cause recurrent urinary tract infections, and subsequent chronic interstitial nephritis is attributed to chronic pyelonephritis. Moreover, high-pressure sterile reflux impairs normal renal growth. Combined, this leads to patchy interstitial scarring, tubular atrophy, and loss of nephron mass and is termed reflux nephropathy. In some cases—especially those with staghorn calculi—xanthogranulomatous pyelonephritis causes suppurative destruction of renal tissue. In adults, long-term complications of chronic pyelonephritis include hypertension, which may be severe (Beck, 2015; Diamond, 2012).

Perhaps half of women with reflux nephropathy were treated during childhood for renal infections. Many also had surgical correction of reflux as children, and these women commonly have bacteriuria when pregnant (Mor, 2003). In the other half of women with reflux nephropathy, a clear history of recurrent cystitis, acute pyelonephritis, or obstructive disease is lacking. Reports describing 939 pregnancies in 379 women with reflux nephropathy indicate that impaired renal function and bilateral renal scarring were associated with increased maternal complications (El-Khatib, 1994; Jungers, 1996; Köhler, 2003). Chronic renal disease and pregnancy outcome are discussed in Chronic Kidney Disease.

Kidney stones develop in up to 9 percent of women during their lifetime with an average age of onset in the third decade (Curhan, 2015). Calcium salts make up approximately 90 percent of stones, and hyperparathyroidism should be excluded. Although calcium oxalate stones in young nonpregnant women are most common, most stones in pregnancy—65 to 75 percent—are calcium phosphate or hydroxyapatite (Ross, 2008; Tan, 2013). Patients who have a stone typically form another one every 2 to 3 years. One study found pregnancy was a risk factor for stone formation (Reinstatler, 2017).

Contrary to past teachings, a low-calcium diet promotes stone formation. Thiazide diuretics diminish stone formation. In general, obstruction, infection, intractable pain, and heavy bleeding are indications for stone removal, discussed later.

Stone Disease During Pregnancy

The incidence of stone disease complicating pregnancy varies. At the low end, the incidence was 0.3 admissions per 1000 pregnancies at Parkland Hospital (Butler, 2000). In an Israeli study, the incidence in nearly 220,000 pregnancies was 0.8 per 1000 (Rosenberg, 2011). In Washington state, the incidence was 1.7 per 1000 pregnancies (Swartz, 2007). Bladder stones are rare, but recurrent infection and labor obstructed by stones have been reported (Ait Benkaddour, 2006; Ruan, 2011).

Data are conflicting whether women with kidney stones have an increased risk for low-birthweight and preterm newborns. In one study of 2239 women with nephrolithiasis compared with normal controls, stones were associated with a significantly elevated preterm delivery rate—10.6 versus 6.4 percent (Swartz, 2007). The more recent nationwide study from Taiwan also found 20- to 40-percent increases in rates of low birthweight and preterm birth (Chung, 2013). In contrast, a study from Hungary reported that pregnancy outcomes, including preterm delivery, were similar in women with stones and normal controls (Banhidy, 2007). Comparable conclusions were drawn from the Israeli study discussed above (Rosenberg, 2011).

Diagnosis

Pregnant women may have fewer symptoms with stone passage because of urinary tract dilatation (Hendricks, 1991; Tan, 2013). That said, more than 90 percent of pregnant women with symptomatic nephrolithiasis present with pain. Gross hematuria is less common than in affected nonpregnant women. It was a presenting symptom in 23 percent of women described by Butler and associates (2000). In another study, however, only 2 percent had gross hematuria (Lewis, 2003). Sonography is usually selected to visualize stones, but many are not detected because hydronephrosis may obscure findings (McAleer, 2004). Transabdominal color Doppler sonography to detect presence or absence of ureteral “jets” of urine into the bladder may exclude obstruction (Asrat, 1998).

If the ureter is abnormally dilated but no stone is seen, then other imaging studies are indicated. While helical computed tomography (CT) scanning is the preferred imaging method for nonpregnant individuals, the associated x-ray exposure has led some to recommend MR imaging as a second-line test in pregnancy (Masselli, 2015). Thus CT scanning is usually avoided during pregnancy if possible (Curhan, 2015; Masselli, 2015). If it is used, the slices can be tailored as needed. White and colleagues (2007) recommend unenhanced helical CT and cite an average fetal radiation dose to be 7 mGy.

Management

Treatment depends on symptoms and gestational age (Semins, 2014). Intravenous hydration and analgesics are given. In up to half of women with symptomatic stones, infection will be identified, and this is treated vigorously as described earlier (Reflux Nephropathy). Although stones infrequently cause symptomatic obstruction during pregnancy, persistent pyelonephritis should prompt a search for obstruction due to nephrolithiasis. Urinary obstruction with concomitant infection is an emergency—“pus under pressure” (Curhan, 2015).

Approximately 65 to 80 percent of symptomatic women will improve with conservative therapy, and the stone usually passes spontaneously (Tan, 2013). Others require an invasive procedure such as ureteral stenting, ureteroscopy, percutaneous nephrostomy, transurethral laser lithotripsy, or basket extraction (Butler, 2000; Johnson, 2012; Semins, 2014). Removal by a flexible basket via cystoscopy, although used less often than in the past, is still a reasonable consideration for pregnant women. In one study, 623 various procedures were performed in 2239 symptomatic pregnant women, but less than 2 percent required surgical exploration (Swartz, 2007). Of other treatments, the need for fluoroscopy limits the utility of percutaneous nephrolithotomy (Toth, 2005). Extracorporeal shock-wave lithotripsy is contraindicated in pregnancy.

Following transplantation, the 1-year graft survival rate is 95 percent for grafts from living donors and 89 percent for those from deceased donors. Survival rates approximately doubled between 1988 and 1996, due in large part to the introduction of cyclosporine and muromonab-CD3 (OKT3 monoclonal antibody) to prevent and treat organ rejection. Since then, mycophenolate mofetil and tacrolimus have further reduced acute rejection episodes, however, the former is considered teratogenic (Briggs, 2014). The National Transplant Pregnancy Registry reports that 23 percent of fetuses exposed to mycophenolate had birth defects (Coscia, 2010). Importantly, resumption of renal function after transplantation promptly restores fertility in reproductive-aged women (Hladunewich, 2011; Rao, 2016). But, more than half of transplant recipients in one study reported that they were not counseled regarding contraception (French, 2013).

Pregnancy Outcomes

Women after transplantation do better with pregnancy than those with end-stage renal disease receiving dialysis (Saliem, 2016). In one review of 2000 pregnancies in transplant recipients, most were treated with cyclosporine and tacrolimus, and approximately 75 percent of pregnancies resulted in a live birth (Coscia, 2010). Studies from other countries describe similar outcomes (Bramham, 2013; Wyld, 2013). In a study from Uruguay, 62 percent of liveborns were preterm (Orihuela, 2016). Two other reports also cited a high prevalence of preterm delivery (Erman Akar, 2015; Stoumpos, 2016). Notably, the incidence of fetal malformations was not increased, except in those who took mycophenolate mofetil (Coscia, 2010).

The incidence of preeclampsia is increased in all transplant recipients (Brosens, 2013). In the UK National Cohort Study, the incidence of preeclampsia was 22 percent (Bramham, 2013). From their review, Josephson and McKay (2011) cite an incidence of a third of pregnancies but question the validity of this frequency. Importantly, in some cases, rejection is difficult to distinguish from preeclampsia. That said, the incidence of rejection episodes approximates 2 to 5 percent (Bramham, 2013; Orihuela, 2016). Viral infections—especially those by polyomavirus hominis 1, also called BK virus, are frequent. In kidney transplant recipients, this virus can cause nephropathy and graft loss, and affected patients generally have an asymptomatic decline in renal function (Wright, 2016). Gestational diabetes is also found in approximately 5 percent of transplant recipients. Both are likely related to immunosuppression therapy. Similar outcomes are reported by other investigators (Al Duraihimh, 2008; Cruz Lemini, 2007; Ghafari, 2008).

Several requisites should be satisfied by renal transplantation patients before attempting pregnancy (Josephson, 2011; López, 2014). First, women should be in good general health for at least 1 to 2 years after transplantation. Also, renal function should be stable and without severe renal insufficiency. Thus, serum creatinine is <2 mg/dL and preferably <1.5 mg/dL, and proteinuria is <500 mg/d. Evidence for graft rejection should be absent for 6 months, and pyelocalyceal distention by urography should not be seen. Moreover, hypertension should be absent or well controlled. And last, women should be taking no teratogenic drugs, and drug therapy should be reduced to maintenance levels.

Cyclosporine, tacrolimus, prednisone, and azathioprine are given routinely to renal transplantation recipients (Jain, 2004; López, 2014). Cyclosporine blood levels decline during pregnancy, although this was not reported to be associated with rejection episodes (Aktürk, 2015; Kim, 2015). Unfortunately, these agents are nephrotoxic and also may cause renal hypertension. In fact, they likely contribute substantively to chronic renal disease that develops in 10 to 20 percent of patients with nonrenal solid-organ transplantation (Goes, 2007). Concern persists regarding the possible late effects in offspring subjected to immunosuppressive therapy in utero. These include malignancy, germ cell dysfunction, and malformations in the children of the offspring. In addition, cyclosporine is secreted in breast milk (Moretti, 2003).

Finally, although pregnancy-induced renal hyperfiltration theoretically may impair long-term graft survival, Sturgiss and Davison (1995) found no evidence for this in a case-control study of 34 allograft recipients followed for a mean of 15 years. Others have reported similar findings (Debska-Ślizień, 2014; Stoumpos, 2016).

Management

Close surveillance is necessary. Covert bacteriuria is treated, and if it is recurrent, suppressive therapy is given for the remainder of the pregnancy. Serial hepatic enzyme concentrations and blood counts are monitored for toxic effects of azathioprine and cyclosporine. Some recommend measurement of serum cyclosporine levels. Gestational diabetes is more common if corticosteroids are taken, and overt diabetes must be excluded with glucose tolerance testing done at approximately 26 weeks’ gestation. Surveillance for opportunistic infections from herpesvirus, cytomegalovirus, and toxoplasmosis is important because these infections are common. Some recommend surveillance for BK virus, however, treatment is problematic (Josephson, 2011).

Renal function is monitored, and the GFR usually increases 20 to 25 percent. If a significant rise in the serum creatinine level is detected, then its cause must be determined. Possibilities include acute rejection, cyclosporine toxicity, preeclampsia, infection, and urinary tract obstruction. Evidence of pyelonephritis or graft rejection should prompt aggressive management. Imaging studies and kidney biopsy may be indicated. The woman is carefully monitored for development or worsening of underlying hypertension, and especially superimposed preeclampsia. Management of hypertension during pregnancy is the same as for patients without a transplant.

Because of increased incidences of fetal-growth restriction and preterm delivery, vigilant fetal surveillance is indicated (Chaps. 42, Diagnosis and 44, Fetal-Growth Restriction Recognition). Although cesarean delivery is reserved for obstetrical indications, occasionally the transplanted kidney obstructs labor. In all women with a renal transplant, the cesarean delivery rate exceeds 60 percent (Bramham, 2013; Rocha, 2013).

This usually autosomally dominant systemic disease primarily affects the kidneys. The disease is found in 1 in 800 live births and causes approximately 5 to 10 percent of end-stage renal disease in the United States. Although genetically heterogeneous, almost 85 percent of cases are due to PKD1 gene mutations on chromosome 16, and the other 15 percent to PKD2 mutations on chromosome 4 (Zhou, 2015). Prenatal diagnosis is available if the mutation has been identified in a family member or if linkage is established in the family.

Renal complications are more common in men than in women, and symptoms usually appear in the third or fourth decade. Flank pain, hematuria, proteinuria, abdominal masses, and associated calculi and infection are common. Hypertension develops in 75 percent, and progression to renal failure is a major problem. Superimposed acute kidney injury may also develop from infection or obstruction from ureteral angulation by cyst displacement.

Other organs are frequently involved. Asymptomatic hepatic cysts coexist in a third of patients with polycystic kidneys. Hepatic involvement is more common and more aggressive in women, and massive polycystic liver disease is almost exclusively found in multiparous women (Zhou, 2015). Approximately 10 percent of patients with polycystic kidney disease die from rupture of an associated intracranial berry aneurysm. Up to a fourth of patients have cardiac valvular lesions that involve valve prolapse or incompetence.

Pregnancy Outcomes

Because of its generally late onset, adult polycystic kidney disease is uncommon in pregnancy (Banks, 2015). The prognosis for pregnancy in these women depends on the degree of associated hypertension and renal insufficiency. Urinary tract infections are common. One study compared pregnancy outcomes in 235 affected women who had 605 pregnancies with those of 108 unaffected family members who had 244 pregnancies (Chapman, 1994). Composite perinatal complication rates were similar—33 versus 26 percent. However, hypertension, including preeclampsia, was significantly more frequent in women with polycystic kidneys. Pregnancy does not seem to accelerate the natural disease course (Lindheimer, 2007b).

The glomerulus and its capillaries are subject to various conditions and stimuli that can lead to acute and chronic diseases. Glomerular damage can be caused by toxins or infections or from systemic diseases that include hypertension, diabetes, or systemic lupus erythematosus (Lewis, 2015). It may also be idiopathic. When there is capillary inflammation, the process is termed glomerulonephritis, and often, an autoimmune process is involved.

Persistent glomerulonephritis eventually leads to worsening renal function. Progression is variable and often does not manifest until chronic renal insufficiency is diagnosed. Lewis and Neilson (2015) group glomerular injuries into six syndromes based on clinical patterns (Table 53-3). Within each of these categories, there are disorders encountered in young women, and thus, these may antedate or first appear during pregnancy.

Acute Nephritic Syndromes

Acute glomerulonephritis may result from any of several causes (see Table 53-3). The clinical presentation usually includes hypertension, hematuria, red-cell casts, pyuria, and proteinuria. Varying degrees of renal insufficiency and salt and water retention result in edema, hypertension, and circulatory congestion (Lewis, 2015). The prognosis and treatment of nephritic syndromes depends on their etiology. Some recede spontaneously or with treatment. However, in some patients, rapidly progressive glomerulonephritis leads to end-stage renal failure, whereas in others, chronic glomerulonephritis develops with slowly progressive renal disease.

Lupus nephritis identified before pregnancy has a 50- percent chance of flaring during pregnancy (Koh, 2015). IgA nephropathy, also known as Berger disease, is the most common form of acute glomerulonephritis worldwide (Wyatt, 2013). The isolated form occurs sporadically, and it may be related to Henoch-Schönlein purpura as the systemic form (Donadio, 2002). Isolated nephritis may be due to anti-glomerular basement membrane (anti-GBM) antibodies. These may also involve the lungs to manifest as a pulmonary-renal syndrome with alveolar hemorrhage, which is termed Goodpasture syndrome (Friend, 2015; Huser, 2015).

Pregnancy

Acute nephritic syndromes during pregnancy can be difficult to differentiate from severe preeclampsia or eclampsia (Cabiddu, 2016). One example is systemic lupus erythematosus with a flare during the second half of pregnancy (Bramham, 2012; Zhao, 2013). In some of these cases, renal biopsy is sometimes needed to determine etiology and direct management (Lindheimer, 2007a; Ramin, 2006).

Whatever the underlying etiology, acute glomerulonephritis has profound effects on pregnancy outcome. One older study described 395 pregnancies in 238 women with primary glomerulonephritis diagnosed before pregnancy (Packham, 1989). The most frequent lesions on biopsy were membranous glomerulonephritis, IgA glomerulonephritis, and diffuse mesangial glomerulonephritis. Although most of these women had normal renal function, half developed hypertension, a fourth were delivered preterm, and the perinatal mortality rate after 28 weeks’ gestation was 80 per 1000. As expected, the worst perinatal outcomes were in women with impaired renal function, early or severe hypertension, and nephrotic-range proteinuria. Similar outcomes have been reported for pregnancies in women with IgA nephropathy. From their review of more than 300 such pregnancies, Lindheimer and colleagues (2000) concluded that pregnancy outcome was related to the degree of renal insufficiency and hypertension. Liu and coworkers (2014) reached similar conclusions.

Nephrotic Syndromes

Heavy proteinuria is the hallmark of the nephrotic syndromes. These result from several primary and secondary kidney disorders that cause immunological or toxin-mediated injury with glomerular capillary wall breakdown to allow excessive filtration of plasma proteins. In addition to heavy urine protein excretion, the syndrome is characterized by hypoalbuminemia, hypercholesterolemia, and edema. There frequently is hypertension, and along with albumin nephrotoxicity, renal insufficiency eventually develops.

Some of the more frequent causes of the nephrotic syndrome are minimal change disease (10–15 percent), focal segmental glomerulosclerosis (35 percent), membranous glomerulonephritis (30 percent), and diabetic nephropathy. In most cases, renal biopsy will disclose microscopic abnormalities that may help direct treatment (Chen, 2015; Lo, 2014). Edema is problematic, especially during pregnancy. Normal amounts of dietary protein of high biological value are encouraged. The incidence of thromboembolism is increased and varies with the severity of hypertension, proteinuria, and renal insufficiency (Stratta, 2006). Although both arterial and venous thromboses may develop, renal vein thrombosis is particularly worrisome. The value, if any, of prophylactic anticoagulation is unclear. Some cases of nephrosis from primary glomerular disease respond to glucocorticosteroids and other immunosuppressants or cytotoxic drug therapy. In most of those cases caused by infection or drugs, proteinuria recedes when the underlying cause is corrected.

Pregnancy

Maternal and perinatal outcomes in women with the nephrotic syndromes depend on its underlying cause and severity. Whenever possible, these should be ascertained, and renal biopsy may be indicated to determine if the etiology will respond to treatment. Half of women with nephrotic-range proteinuria will have a rise in daily protein excretion as pregnancy progresses (Packham, 1989). In women with nephrosis cared for at Parkland Hospital, we reported that two thirds had protein excretion that exceeded 3 g/d (Stettler, 1992). At the same time, however, if these women had only mild degrees of renal dysfunction, they had normally augmented GFR across pregnancy (Cunningham, 1990).

Management of edema during pregnancy can be particularly challenging as it is intensified by normally increasing hydrostatic pressure in the lower extremities. In some women, massive vulvar edema may develop. An example of massive vulvar edema associated with the nephrotic syndrome caused by secondary syphilis is shown in Figure 53-3. Another major problem is that up to half of these women have chronic hypertension that may require treatment. In these, as well as in previously normotensive women, preeclampsia is common and often develops early in pregnancy.

Most women with nephrotic syndromes who do not have severe hypertension or renal insufficiency will have successful pregnancy outcomes. Conversely, if there is renal insufficiency, moderate to severe hypertension, or both, the prognosis is much worse. In a group of such women with 65 pregnancies cared for at Parkland Hospital, complications were frequent (Stettler, 1992). Protein excretion during pregnancy averaged 4 g/d, and a third of the women had classic nephrotic syndrome. There was some degree of renal insufficiency in 75 percent, chronic hypertension in 40 percent, and persistent anemia in 25 percent. Importantly, preeclampsia developed in 60 percent, and 45 percent had preterm deliveries. Even so, after excluding abortions, 53 of 57 neonates were born alive. In another series, fetal-growth restriction was noted in a third of pregnancies in affected women (Stratta, 2006).

Serious long-term adverse outcomes are a risk for women identified to have nephrotic syndromes either before or during pregnancy (Su, 2017). In our series above, at least 20 percent of women followed for 10 years progressed to end-stage renal disease (Stettler, 1992). Similarly, in another group of 15 women, by 2 years postpartum, three had died, three had developed chronic renal failure, and two had progressed to end-stage renal disease (Chen, 2001). Of predictors, serum creatinine level >1.4 mg/dL and 24-hour protein excretion >1 g/d are associated with the shortest renal survival times following pregnancy (Imbasciati, 2007).

This describes a pathophysiological process that can progress to end-stage renal disease. The National Kidney Foundation describes six stages of chronic kidney disease defined by decreasing GFR. It progresses from stage 0—GFR >90 mL/min/1.73 m² to stage 5—GFR <15 mL/min/1.73 m². Several diseases can worsen renal function, and many result from one of the glomerular diseases discussed earlier. Those that most frequently lead to end-stage disease requiring dialysis and kidney transplantation and their approximate percentages include: diabetes, 35 percent; hypertension, 25 percent; glomerulonephritis, 20 percent; and polycystic kidney disease, 15 percent (Abboud, 2010; Bargman, 2015).

Most reproductive-aged women with these diseases have varying degrees of renal insufficiency, proteinuria, or both. To counsel regarding fertility and pregnancy outcome, the degree of renal functional impairment and of associated hypertension are assessed. Successful pregnancy outcome in general may be more related to these two factors than to the specific underlying renal disorder. A general prognosis can be estimated by considering women with chronic renal disease in arbitrary categories of renal function (Davison, 2011). These include normal or mild impairment—defined as a serum creatinine <1.5 mg/dL; moderate impairment—defined as a serum creatinine 1.5 to 3.0 mg/dL; and severe renal insufficiency—defined as a serum creatinine >3.0 mg/dL. Although some have suggested adopting the classification of the National Kidney Foundation, others recommend using the older categories (Davison, 2011; Piccoli, 2010a, 2011). Thus, the obstetrician is ideally familiar with both.

Pregnancy and Chronic Renal Disease

Most women have relatively mild renal insufficiency, and its severity along with any underlying hypertension is prognostic of pregnancy outcome. Renal disease with comorbidities secondary to a systemic disorder—for example, diabetes or systemic lupus erythematosus—portends a worse prognosis (Davison, 2011; Koh, 2015). For all women with chronic renal disease, the incidences of hypertension and preeclampsia, preterm and growth-restricted newborns, and other problems are high (Kendrick, 2015). Despite these, the National High Blood Pressure Education Program (2000) concluded that the prognosis has substantively improved since the 1980s. This has been verified by several reviews (Hladunewich, 2016a; Nevis, 2011; Ramin, 2006).

Loss of renal tissue is associated with compensatory intrarenal vasodilation and hypertrophy of the surviving nephrons. The resultant hyperperfusion and hyperfiltration eventually damage surviving nephrons to cause nephrosclerosis and worsening renal function. With mild renal insufficiency, pregnancy causes greater augmentation of renal plasma flow and GFR (Baylis, 2003; Helal, 2012). With progressively declining renal function, there is little, if any, augmented renal plasma flow. In one study, only half of women with moderate renal insufficiency demonstrated a pregnancy-augmented GFR, and women with severe disease had no increase (Cunningham, 1990).Importantly, severe chronic renal insufficiency curtails normal pregnancy-induced hypervolemia. Blood volume expansion during pregnancy is related to disease severity and correlates inversely with serum creatinine concentration. As shown in Figure 53-4, women with mild to moderate renal dysfunction have normal blood volume expansion that averages 55 percent. With severe renal insufficiency, however, volume expansion averages only 25 percent, which is similar to that seen with hemoconcentration from eclampsia. In addition, these women have variable degrees of chronic anemia due to intrinsic renal disease.

Renal Disease with Preserved Function

In some women, although glomerular disease has not yet caused renal dysfunction, incidences of pregnancy complications are still increased. As shown in Table 53-4, these problems are less frequent than in cohorts of women with moderate and severe renal insufficiency. Two earlier studies illustrate this. In one describing 123 pregnancies in women with biopsy-proven glomerular disease, only a few of the women had renal dysfunction, yet 40 percent developed obstetrical or renal complications (Surian, 1984). In another study of 395 pregnancies in women with preexisting glomerulonephritis and minimal renal insufficiency, impaired renal function developed in 15 percent during pregnancy, and 60 percent had worsening proteinuria (Packham, 1989). Only 12 percent had antecedent chronic hypertension, however, more than half of the 395 pregnancies were complicated by hypertension. The perinatal mortality rate was 140 per 1000, but even without early-onset or severe hypertension or nephrotic-range proteinuria, the perinatal death rate was 50 per 1000. Importantly, in 5 percent of these women, worsening renal function was permanent.

Chronic Renal Insufficiency

In women with chronic kidney disease who also have renal insufficiency, adverse outcomes are generally directly related to the degree of renal impairment. Outcomes of women with moderate versus severe renal insufficiency are usually not separated (Table 53-5). That said, Piccoli and associates (2010a) described 91 pregnancies complicated by stage 1 chronic kidney disease. Primarily because of hypertension, 33 percent were delivered preterm, and 13 percent had fetal-growth restriction. Alsuwaida and colleagues (2011) reported similar observations. Other investigators have described pregnancies complicated by moderate or severe renal insufficiency (Cunningham, 1990; Imbasciati, 2007; Zhang, 2015). Despite a high incidence of chronic hypertension, anemia, preeclampsia, preterm delivery, and fetal-growth restriction, perinatal outcomes were generally acceptable. As shown in Figure 53-5, fetal growth is frequently impaired and related to renal dysfunction severity.

Management

Prenatal care is tailored for women with chronic renal disease. Frequent monitoring of blood pressure is paramount, and serum creatinine levels, protein/creatinine ratio, and 24-hour protein excretion are quantified as indicated. Bacteriuria is treated to decrease the risk of pyelonephritis and further nephron loss. Protein-rich diets are recommended (Jim, 2016; Lindheimer, 2000). In some women with anemia from chronic renal insufficiency, a response is seen with recombinant erythropoietin, however, hypertension is a common side effect. Serial sonography is performed to follow fetal growth. The differentiation between worsening hypertension and superimposed preeclampsia is problematic. Preliminary data indicate that the angiogenic biomarkers placental growth factor (PlGF) and its soluble antiangiogenic receptor (sFlt-1) may be useful to separate chronic from gestational hypertension. This is described in Chapter 40 (Endothelial Cell Injury).

Long-Term Effects

In some women, pregnancy may accelerate chronic renal disease progression by increasing hyperfiltration and glomerular pressure to worsen nephrosclerosis (Baylis, 2003; Helal, 2012). This is more likely in women with severe chronic renal insufficiency (Abe, 1991; Jones, 1996). For example, Jungers and associates (1995) reported few long-term pregnancy-related adverse effects in 360 women with chronic glomerulonephritis and antecedent normal renal function. However, at 1 year after pregnancy, Jones and Hayslett (1996) reported that 10 percent of such women with moderate or severe renal insufficiency had developed end-stage renal failure—stage 5 chronic kidney disease. In a study from Parkland Hospital, we found that 20 percent of pregnant women with similar insufficiency had developed end-stage renal failure by a mean of 4 years (Cunningham, 1990). Similar findings in women with a median follow-up of 3 years were described by Imbasciati and coworkers (2007). By this time, end-stage disease was apparent in 30 percent of women whose serum creatinine was ≥1.4 mg/dL and who had proteinuria >1 g/d. Chronic proteinuria is also a marker for subsequent development of renal failure. In another report from Parkland Hospital, 20 percent of women with chronic proteinuria discovered during pregnancy progressed to end-stage renal failure within several years (Stettler, 1992).

Dialysis During Pregnancy

Significantly impaired renal function is accompanied by subfertility that may be corrected with chronic renal replacement therapy—either hemodialysis or peritoneal dialysis (Hladunewich, 2016b; Shahir, 2013). Not unexpectedly, these pregnancies can be complicated. In one review of 131 cases, mean fetal birthweights were higher in women who conceived while undergoing dialysis—1530 g versus 1245 g—than in women who conceived before starting dialysis (Chou, 2008). This was also true for 77 pregnancies described by Jesudason and coworkers (2014). Similar outcomes from several reports are shown in Table 53-5.

Outcomes are similar with either hemodialysis or peritoneal dialysis. Thus, for the woman already undergoing either method, it seems reasonable to continue that method with consideration for its increasing frequency. In the woman who has never been dialyzed, the threshold for initiation during pregnancy is unclear. Lindheimer and colleagues (2007a) recommend dialysis when serum creatinine levels are between 5 and 7 mg/dL. Because it is imperative to avoid abrupt volume changes that cause hypotension, dialysis frequency may be extended to five to six times weekly (Reddy, 2007).

Certain protocols emphasize attention to replacement of substances lost through dialysis (Jim, 2016). Multivitamin doses are doubled, and calcium and iron salts are provided along with sufficient dietary protein and calories. Chronic anemia is treated with erythropoietin. To meet pregnancy changes, extra calcium is added to the dialysate along with less bicarbonate.Maternal complications are common and include severe hypertension, placental abruption, heart failure, and sepsis. In a review of 90 pregnancies in 78 women, as well as those shown in Table 53-5, high incidences of maternal hypertension and anemia, preterm and growth-restricted infants, stillbirths, and hydramnios were reported (Piccoli, 2010b).

Previously termed acute renal failure, acute kidney injury (AKI) is now used to describe suddenly impaired kidney function with retention of nitrogenous and other waste products normally excreted by the kidneys (Waikar, 2015). Severe AKI associated with pregnancy is less frequent today. For example, in a 6-year period, the overall incidence at the Mayo Clinic was 0.4 percent (Gurrieri, 2012). It is even less common for women who require dialysis—1 case per 10,000 births (Hildebrand, 2015). But, it still occasionally causes significant obstetrical morbidity, and women who require acute dialysis have increased maternal mortality rates (Kuklina, 2009; Van Hook, 2014). Outcomes are available from four older studies comprising a total of 266 women with renal failure (Drakeley, 2002; Nzerue, 1998; Sibai, 1990; Turney, 1989). Nearly 70 percent had preeclampsia, 50 percent had obstetrical hemorrhage, and 30 percent had a placental abruption. Almost 20 percent required dialysis, and the maternal mortality rate was 15 percent.

Although obstetrical cases of AKI that require dialysis have become less prevalent, acute renal ischemia is still often associated with severe preeclampsia and hemorrhage (Gurrieri, 2012; Jim, 2017). Particularly contributory are HELLP (hemolysis, elevated liver enzymes, low platelet levels) syndrome and placental abruption (Audibert, 1996; Drakely, 2002). Septicemia is another frequent comorbidity, especially in resource-poor countries (Acharya, 2013; Srinil, 2011; Zeeman, 2003). AKI is also common in women with acute fatty liver of pregnancy (Sibai, 2007). Some degree of renal insufficiency was found in virtually all of 52 such women cared for at Parkland Hospital (Nelson, 2013). Another woman from Parkland Hospital developed AKI from dehydration caused by severe hyperemesis gravidarum at 15 weeks (Hill, 2002). Other causes include thrombotic microangiopathies (Balofsky, 2016; Ganesan, 2011) (Chap. 56, Thrombotic Microangiopathies).

Diagnosis and Management

In most women, AKI develops postpartum, thus management is usually not complicated by fetal considerations. An abrupt rise in serum creatinine level is most often due to renal ischemia. Oliguria is an important sign. In obstetrical cases, both prerenal and intrarenal factors are often contributory. For example, with total placental abruption, severe hypovolemia from massive hemorrhage is common, and preexistent renal ischemia from preeclampsia is often comorbid. In addition, disseminated intravascular coagulopathy may be contributory.

When azotemia is evident and severe oliguria persists, some form of renal replacement treatment is indicated. Hemofiltration or dialysis is initiated before marked deterioration occurs. Hemodynamic measurements are normalized. Importantly, medication doses are adjusted, and magnesium sulfate, iodinated contrast agents, aminoglycosides, and nonsteroidal antiinflammatory drugs (NSAIDs) are prominent examples (Waikar, 2015). Early dialysis appears to reduce the maternal mortality rate appreciably and may enhance the extent of renal function recovery. With time, renal function usually returns to normal or near normal.

Prevention

AKI in obstetrics is most often due to acute blood loss, especially that associated with preeclampsia. Thus, it may often be prevented by the following means:

1. Prompt and vigorous volume replacement with crystalloid solutions and blood in instances of massive hemorrhage, such as in placental abruption, placenta previa, uterine rupture, and postpartum uterine atony (Chap. 41, Hypovolemic Shock).

2. Delivery or termination of pregnancies complicated by severe preeclampsia or eclampsia, and careful blood transfusion if loss is more than average (Chap. 40, Blood Volume).

3. Close observation for early signs of sepsis syndrome and shock in women with pyelonephritis, septic abortion, chorioamnionitis, or sepsis from other pelvic infections (Chap. 47, Sepsis Syndrome).

4. Avoidance of loop diuretics to treat oliguria before ensuring that blood volume and cardiac output are adequate for renal perfusion.

5. Judicious use of vasoconstrictor drugs to treat hypotension, and only after it has been determined that pathological vasodilatation is the cause.

Irreversible ischemic renal failure caused by acute cortical necrosis is rare now in obstetrics (Frimat, 2016). Before widespread availability of dialysis, it complicated a fourth of obstetrical renal failure cases (Grünfeld, 1987; Turney, 1989). Most cases followed placental abruption, preeclampsia-eclampsia, and endotoxin-induced shock. Once common with septic abortion, this is a rare cause in this country today (Lim, 2011; Srinil, 2011). Histologically, the lesion appears to result from thrombosis of segments of the renal vascular system. The lesions may be focal, patchy, confluent, or gross. Clinically, renal cortical necrosis follows the course of AKI, and its differentiation from acute tubular necrosis is not possible during the early phase. The prognosis depends on the extent of the necrosis. Recovery of function is variable, and stable renal insufficiency may result (Lindheimer, 2007a).

Obstructive Renal Failure

Rarely, bilateral ureteral compression by a very large pregnant uterus is greatly exaggerated. Resultant ureteral obstruction in turn may cause severe oliguria and azotemia. An extreme example is shown in Figure 53-6. In their series of 13 obstruction cases, Brandes and Fritsche (1991) described one woman with twins who developed anuria and a serum creatinine level of 12.2 mg/dL at 34 weeks’ gestation. After amniotomy, urine flow resumed at 500 mL/hr, and her serum creatinine levels rapidly dropped to normal range. Eckford and Gingell (1991) described 10 women in whom ureteral obstruction was relieved by stenting. The stents were left in place for a mean of 15.5 weeks and removed 4 to 6 weeks postpartum. Others have reported similar experiences (Sadan, 1994; Satin, 1993). Partial ureteral obstruction may be accompanied by fluid retention and significant hypertension. When the obstructive uropathy is relieved, diuresis ensues and hypertension dissipates. In our experience, women with previous urinary tract surgery for reflux are more likely to have such obstructions.

Urethral Diverticulum

Although infrequently complicating pregnancy, this type of diverticulum originates from an enlarging paraurethral gland abscess that ruptures into the urethral lumen. As infection clears, the remaining dilated diverticular sac and its ostium into the urethra persist. Urine collecting within and dribbling from the sac, pain, a palpable mass, and recurrent urinary infections may be associated findings. In general, a diverticulum is managed expectantly during pregnancy. Rarely, drainage may be necessary, or surgery required (Iyer, 2013). If additional antepartum evaluation is needed, MR imaging is preferred for its superior soft tissue resolution and ability to define complex diverticula (Dwarkasing, 2011; Pathi, 2013).

Urogenital Tract Fistulas

Fistulas found during pregnancy likely existed previously, but in rare cases, they form during pregnancy. In developed countries, vesicovaginal or cervicovaginal fistula following a McDonald cerclage has been reported (Massengill, 2012; Zanconato, 2015). These fistulas may also form with prolonged obstructed labor that is more often seen in resource-poor countries (Cowgill, 2015). In these cases, the genital tract is compressed between the fetal head and bony pelvis. Brief pressure is not significant, but prolonged pressure leads to tissue necrosis with subsequent fistula formation (Wall, 2012). Vesicouterine fistulas can develop after prior vaginal or cesarean delivery (DiMarco, 2006; Harfouche, 2014; Manjunatha, 2012). Rarely, vesicocervical fistula can follow cesarean delivery or may form if the anterior cervical lip is compressed against the symphysis pubis (Dudderidge, 2005). Finally, an ileouterine fistula from a degenerating posterior wall fibroid tumor has been described (Shehata, 2016).