of Urolithiasis in Pregnancy

Imaging study

Radiation dose (mGy)

Sensitivity (%)

Specificity (%)

Ultrasound

34–86

IVP (3 film)

1.7–10

X-ray KUB

1.4–4.2

44–77

80–87

CT (conventional)

8–49

>96

>98

CT (low dose)

≤7

>96

MR urography

100

IVP intravenous pyelogram, KUB kidneys, ureters, bladder, CT computed tomography, MR magnetic resonance

For pregnant patients with potential renal colic, US is the preferred initial imaging modality for evaluation. It has many advantages including that it is inexpensive, easily obtained, has no ionizing radiation, and is safe to both the mother and the fetus. However, the sensitivity of ultrasound to accurately detect urolithiasis during pregnancy is operator dependent and highly variable ranging from 34% to 86%, with a specificity of 86% [26]. Gestational hydronephrosis can complicate the diagnosis as it can be challenging to discriminate between acute ureteric obstruction and physiologic hydronephrosis if a definitive stone is not visible (Fig. 13.1a, b) [8, 14]. Further difficulty with ultrasound can occur secondary to the patient’s body habitus, position of the fetus, or specific location of the calculi within the ureter. The location of hydroureteronephrosis can help distinguish between pathologic and physiologic obstruction; for example, severe left hydronephrosis or hydroureter distal to the iliac vessels is suggestive of acute ureteric obstruction from a calculus [35].

../images/461848_1_En_13_Chapter/461848_1_En_13_Fig1_HTML.jpg — Fig. 13.1

Ultrasound images of right distal ureteric calculi in pregnancy. (a) Retroperitoneal ultrasound demonstrating right hydronephrosis. (b) Retroperitoneal ultrasound demonstrating right proximal hydroureter. (c) Endovaginal ultrasound demonstrating absence of right ureteral jet. (d) Endovaginal ultrasound demonstrating echogenic right distal ureteric calculi with ureter dilated proximal to the calculi

A number of adjunct techniques have been employed in order to try and improve the accuracy of US including urinary jets , endovaginal ultrasound , and resistive indices (RI) . Non-visualization of a urinary jet is suggestive of an obstructing calculus (Fig. 13.1c). However, up to 13% of pregnant patients without urolithiasis will still have absence of their urinary jet, and it is more commonly absent on the right [36]. Visualization of the urinary jet can be optimized by pre-hydrating the patient before US [37]. Asymmetry of urinary jets is noted in 65% of patients with urolithiasis, though this can be difficult to accurately interpret [38, 39]. Endovaginal US can aid in the visualization of distal ureteric calculi and urinary jets but is contraindicated with prolapsed or ruptured membranes (Fig. 13.1d) [35].

The measurement of RI with Doppler US has been utilized to differentiate between physiologic and pathologic obstructions. RI is defined as the peak diastolic velocity subtracted from the peak systolic velocity and divided by the peak systolic velocity, with an RI of 0.70 or greater, suggestive of pathologic obstruction [40]. However, RI is a non-specific measurement, and there remains controversy regarding the absolute value to serve as a cutoff for obstruction. In addition, RI may be elevated in normal non-obstructed kidneys and can be normal during the early phase of obstruction when there is elevated renal blood flow and vascular dilatation [41]. The combination of an elevated RI and absence of a ureteric jet has been shown to increase the accuracy of US in predicting a ureteric calculus from 56.2% to 71.9% [40].

In certain cases the diagnosis of urolithiasis cannot be definitely made with history, physical examination, and US imaging alone, and consideration must be given to alternative imaging modalities. While every effort should be made to minimize ionizing radiation exposure in the pregnant population, concerns regarding radiation exposure should not prevent a medically indicated diagnostic exam from being performed. Traditionally, KUB or IVP have been second-line imaging modalities when initial evaluation with US has failed to yield a definitive diagnosis. However, with the advent of modern low-dose CT scanning techniques, KUB and IVP have fallen out of favor. Low-dose CT scans provide a highly sensitive and specific test (>96%) for the detection of urolithiasis, with levels of radiation comparable to a KUB or IVP (Fig. 13.2) [42]. In addition, low-dose CT does not require the administration of intravenous iodinated contrast which has been associated with fetal hypothyroidism [33]. The use of diagnostic CT in pregnancy is becoming increasingly more common and has increased by 25% per year from 1997 to 2006 [43].

../images/461848_1_En_13_Chapter/461848_1_En_13_Fig2_HTML.jpg — Fig. 13.2

Low-dose CT images of proximal right ureteric calculi in pregnancy. (a) Right hydronephrosis. (b) Calculi in proximal right ureter with hydroureter

A previous multi-institutional study comparing imaging modalities for the detection of urolithiasis in pregnancy demonstrated that low-dose CT had the highest positive predictive value (96%) [44]. In addition, a recent study examining the use of low-dose CT scans in pregnancy confirmed a very low radiation exposure of only 7.1 mGy [34]. In order to maintain the sensitivity and specificity of low-dose CT scans, above 90% patients should have a BMI of less than 30 [45]. Newer software is currently being investigated that may allow for further reductions in radiation exposure for low-dose CT scans. Currently, the American Urological Association (AUA) recommends low-dose CT scan (<5 mGy) as an appropriate second-line imaging modality for pregnant women in the second and third trimester when initial ultrasound is nondiagnostic [45]. This is based on the recommendation from ACOG that the radiation dose associated with this is well below the suggested threshold of 50 mGy and is not associated with fetal anomalies or loss [33].

Recent evidence has demonstrated that magnetic resonance urography with a T2-weighted half-Fourier acquisition single-shot turbo-spin echo (HASTE) protocol can be utilized for the diagnosis of urinary stone disease in pregnancy (Fig. 13.3). A previous small series evaluating the use of HASTE MRU in the diagnosis of acute ureteric obstruction in pregnancy revealed a high sensitivity (84%), specificity (100%), and diagnostic accuracy (100%) [46]. MRU has multiple advantages including the avoidance of ionizing radiation, the ability to detect non-urologic causes of symptoms, a short acquisition time of approximately 15 min, and no known harmful effects to the fetus [47]. However, its use is limited by high cost, limited availability, and the contraindication of use in patients with metallic implants. Stones do not have a specific signal on MRU which makes their detection somewhat difficult. However, specific findings of ureteric obstruction include direct visualization of a stone at the point of ureteric constriction , renal stranding, perirenal extravasation, renal or ureteric edema, and the “double-kink” sign where there is ureteric constriction present both at the pelvic brim and ureterovesical junction [47]. Gadolinium contrast is not required for MRU and should be avoided in pregnancy as it crosses the placenta and has been associated with neonatal death [48].

../images/461848_1_En_13_Chapter/461848_1_En_13_Fig3_HTML.jpg — Fig. 13.3

MRI image demonstrating right physiological hydronephrosis of pregnancy

The accurate and safe diagnosis of urinary stone disease in pregnancy remains challenging despite significant advances in diagnostic imaging. Low-dose CT has been demonstrated to have the highest positive predictive value for detecting urolithiasis during pregnancy at 96% compared with MRU and US which had positive predictive values of 80% and 77%, respectively [44]. A recent study evaluating renal colic in pregnancy demonstrated a high overall rate of negative ureteroscopy of 14% [44]. The type of preoperative imaging modality utilized significantly affected the rate of negative ureteroscopy. The rate was highest for US alone (23%), followed by US plus MRU (20%), and lowest for US plus low-dose CT (4.3%) [44].

The AUA has published recommendations for diagnostic imaging in the setting of renal colic in pregnancy. US is recommended as the first-line modality for all pregnant women suspected of renal colic given its safe, well-established use in pregnancy and wide availability [45]. If initial US is nondiagnostic, then consideration should be given to non-contrast MRU in the first trimester, or low-dose CT in the second and third trimesters, prior to proceeding with surgical intervention [45]. The clinician must carefully assess the clinical scenario and thoroughly consider potential risks and benefits of different imaging modalities prior to proceeding. Multidisciplinary collaboration between urology, obstetrics, and radiology is helpful in ensuring comprehensive care in this challenging patient population. Further advances in imaging techniques and improved diagnostic algorithms are required in order to prevent unnecessary intervention in this high-risk population.

Management

Management of urolithiasis in pregnancy is complex and challenging given the physiologic changes of pregnancy and the potential complications that can occur from both renal colic and the management of the stone. In the absence of any acute indications, expectant management is the first-line treatment for renal colic in pregnancy. Indications for acute intervention include active infection, progressive renal insufficiency, an obstructed solitary kidney, bilateral renal obstruction, intractable symptoms such as pain or emesis, or signs of imminent obstetrical complications such as preeclampsia or preterm labor. There are several options for intervention including temporizing drainage measures such as insertion of an indwelling ureteral stent or external nephrostomy tube and definitive surgical management with ureteroscopy (Fig. 13.4).

../images/461848_1_En_13_Chapter/461848_1_En_13_Fig4_HTML.png — Fig. 13.4

Algorithm for the diagnosis and management of urolithiasis in pregnancy

Until the mid-2000s, temporary drainage with delay of definitive stone management until the postpartum period was the mainstay of treatment for stone disease in pregnancy. However, this is associated with many disadvantages including the requirement of multiple procedures for frequent tube changes and associated symptoms and discomfort from the drainage tube. Recent technological advances in ureteroscopy including smaller caliber ureteroscopes and the wide adoption of holmium:yttrium-aluminum-garnet (Ho:YAG) lasers have allowed ureteroscopy to become an accepted alternative for patients who fail expectant management. Surgical intervention is best performed during the second trimester of pregnancy when the risk of preterm labor and miscarriage is the lowest [49]. Other treatment modalities of urolithiasis including shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL) are currently contraindicated in pregnancy. Once again, a multidisciplinary approach with the involvement of a urologist, obstetrician, radiologist, neonatologist, and potentially an anesthesiologist if surgical management is planned is highly recommended in order to optimize care for both the mother and fetus.

The first-line treatment for uncomplicated ureteric calculi in pregnancy is expectant management with a trial of spontaneous passage. It has previously been estimated that the rate of spontaneous passage for symptomatic upper tract urinary calculi in pregnancy is 70–80% [28]. In addition, a higher rate of spontaneous passage has been demonstrated in pregnant women compared to their nonpregnant counterparts (81% vs 46%) [18, 25]. This is thought to be secondary to the effects of progesterone during pregnancy which cause smooth muscle relaxation of the urinary collecting system and subsequent ureteral dilatation [28]. However, this elevated rate of spontaneous passage has recently been questioned with a more recent study demonstrating a spontaneous passage rate of only 47% [27]. This suggests that the initial high rates of spontaneous passage may have been an overestimate secondary to erroneous diagnosis and incomplete follow-up. Similar to the nonpregnant population, the rate of spontaneous passage is correlated with the location of the stone, and a previous study has demonstrated a higher spontaneous passage rate for distal ureteric calculi (44.1%) compared with proximal ureteric or ureteropelvic junction stones (27.3%) [40]. Observation with serial US examinations is recommended throughout the duration of the pregnancy while expectant management is being undertaken. If the stone fails to pass during pregnancy, approximately 50% of patients will pass their stone within the 1st month postpartum [28]. Once the patient has delivered, routine management of the stone can be undertaken if it has not already passed.

Expectant management requires aggressive fluid resuscitation and appropriate symptom management with analgesia and antiemetics. Ideally, fluid resuscitation is performed through oral supplementation; however, fluids can be administered intravenously if there is significant nausea or emesis. Careful consideration must be given to the potential adverse effects to the mother and fetus of any medications administered during pregnancy. For this reason, consultation with obstetrics and pharmacy is highly recommended. Nonsteroidal anti-inflammatory drugs (NSAIDs) are classically recommended as first-line treatment for analgesia in urolithiasis in the nonpregnant population given their effectiveness in managing renal colic and nonnarcotic quality. However, the use of NSAIDs is contraindicated in pregnancy due to the risk of premature closure of the patent ductus arteriosus during the third trimester and their association with fetal pulmonary hypertension, oligohydramnios, cardiac malformations, and miscarriage [50]. Oral agents including codeine and oxycodone have been associated with teratogenic effects in the first trimester and are not recommended for use in pregnancy [51]. For less severe pain, acetaminophen is a safe option with no known adverse effects to the mother or fetus [28]. For more severe pain, small, frequent doses of opioids such as morphine are utilized and are considered to be the mainstay of analgesia during pregnancy [51]. However, chronic use can result in intrauterine growth retardation , premature labor , and fetal narcotic addiction [27, 28].

Medical expulsive therapy (MET) utilizes α-blockers or calcium channel blockers to facilitate the spontaneous passage of ureteric calculi and is commonly employed in the nonpregnant population [52]. However, controversy exists regarding the use of MET as high-quality evidence exists both in support and opposition to its use, and there is currently no consensus. In addition, it is uncertain whether the smooth muscle relaxation provided by MET would be of benefit in pregnancy when there is already physiologic dilatation secondary to elevated progesterone levels [14]. Currently, both α-blockers and calcium channel blockers are classified as category B pregnancy medications and thought to be safe with no harmful effects having been demonstrated in humans to date [53].

A recent retrospective matched cohort study investigated the safety and efficacy of MET in pregnancy and found no association with adverse maternal or fetal outcomes. There was a nonstatistical increase in the rate of sudden infant death syndrome (SIDS) in the tamsulosin-treated group which was felt to be spurious; however, further investigation is required [54]. This study also demonstrated a 24% increase in the rate of spontaneous passage with MET; however, the time to spontaneous passage was longer in the MET treatment group [54]. While this recent study is promising that the use of MET in pregnancy is both safe and efficacious, more rigorous evidence is required before the use of MET in pregnancy can be widely adopted. Despite the limited and conflicting evidence available on the use of MET, a recent worldwide survey found that 97.6% of urologists utilize MET in stone disease and 44.3% specifically utilize it in the setting of pregnancy [55]. Currently the AUA and Endourological Society recommend that if the use of MET is being considered in a pregnant patient, careful patient counselling should be undertaken, and the patient should be informed that these medications have not been well studied for use in pregnancy and are being utilized for an “off-label” purpose [52].

When acute indications for stone treatment are present, temporizing drainage with either an indwelling ureteral stent or an external nephrostomy tube may be utilized. There are distinct advantages and disadvantages to each method of urinary drainage; and the selection of drainage method ultimately depends on the specific clinical scenario, availability of resources, and surgeon and patient preference. Both drainage devices carry a risk of infection, dislodgement, blockage, or encrustation [56]. Indwelling ureteric stents can cause lower urinary tract voiding symptoms as well as suprapubic and flank discomfort. Lower urinary tract symptoms caused by ureteric stents can be difficult to manage in pregnancy given that anticholinergics are contraindicated. In comparison, external nephrostomy tubes can also be associated with flank discomfort and require additional care as there is an external component to the tube. Nephrostomy tube insertion has a high success rate, results in rapid decompression of the collecting system, and avoids ureteric manipulation. For these reasons nephrostomy tube insertion may be preferred in the setting of sepsis [57]. However, the insertion of a nephrostomy tube is contraindicated in the setting of anticoagulation given the risk of renal hemorrhage.

Both nephrostomy tubes and ureteric stents can be inserted with minimal anesthesia. Insertion of a ureteric stent is typically performed under limited fluoroscopic guidance and for this reason may not be the ideal choice of drainage method during the first trimester [56]. Although insertion of ureteric stents under ultrasound guidance has been described, expertise in this technique is limited [56]. In contrast, nephrostomy tubes are typically inserted under ultrasound guidance and may be preferred during the first trimester. Evidence has demonstrated that either drainage modality has equivalent patient outcomes [57]. Due to the metabolic changes that occur during pregnancy, foreign bodies in the urinary tract are prone to accelerated encrustation. This necessitates the frequent exchange of either ureteric stents or nephrostomy tubes every 4–6 weeks during pregnancy [17].

Percutaneous nephrolithotomy is contraindicated during pregnancy due to the need for prolonged anesthetic and fluoroscopy times as well as prone positioning. Successful PCNL during pregnancy has been described utilizing a supine position and ultrasound-guided access, with no complications being reported for these cases [58, 59]. However, if PCNL is required due to a large or complex stone burden, this is best performed in the postpartum period and managed during pregnancy with temporizing drainage with either a nephrostomy tube or stent.

Shockwave lithotripsy is also contraindicated during pregnancy due to potential risks posed to the fetus including miscarriage, congenital malformations, intrauterine growth retardation, and placental displacement [60]. Case reports exist of inadvertent SWL being performed during pregnancy that have resulted in no complications. However, presently there is insufficient evidence to support the safe use of SWL during pregnancy [61].

Ureteroscopy

Definitive stone management with ureteroscopy is a safe and effective treatment option for urolithiasis in pregnancy for patients who fail expectant management. This has been made possible by recent advances in surgical technology including smaller diameter ureteroscopes, the widespread use of intracorporeal lithotripters, and improvements in flexible grasping devices, all of which allow for safe and efficient treatment of stones in all locations. Ureteroscopy in this setting is associated with high stone-free rates and low complication rates for both the mother and fetus. Contraindications include active infection, large stone burden, multiple or bilateral calculi, abnormal anatomy, obstetrical complications, inadequate obstetric, urological or anesthetic resources, or very early or late presentations [62]. In these instances, temporizing drainage with a stent or nephrostomy tube should be utilized, and definitive surgical management of the stone should be delayed. The teratogenic risks of anesthetic agents are significantly higher in the first trimester, and as such ureteroscopy is reserved for the second and third trimesters of pregnancy [50].

Ureteroscopy has been well established to be both safe and effective in pregnancy with stone-free rates comparable to ureteroscopy in nonpregnant patients. A number of case series have demonstrated that ureteroscopy has acceptable stone-free rates of 63–100%, comparable to results in the nonpregnant population (Table 13.2) [18, 63–90]. The safety of ureteroscopy has also been well documented with multiple studies showing a low rate of preterm labor of 0–1% (Table 13.2) [18, 63–90]. In addition, a recent meta-analysis revealed no difference in the incidence of complications such as ureteric injury or urinary tract infection in pregnant patients compared with nonpregnant patients undergoing ureteroscopy [62]. Furthermore, recent evidence has emerged that ureteroscopy may be the safest option for the treatment of uncomplicated ureteric calculi in pregnancy and was associated with the fewest number of complications compared with ureteric stent or nephrostomy tube drainage [91]. A recent study has also demonstrated that ureteroscopy resulted in fewer additional interventions and significantly decreased pain and urinary tract symptoms [92]. In addition, definitive management with ureteroscopy has been shown to be more cost-effective than temporizing drainage with a stent or nephrostomy tube [93].

Table 13.2

Compilation of series examining outcomes of ureteroscopy for the treatment of ureteral stones in pregnancy [18, 63–90]

Author	No. pts	Mean stone size (mm)	Stone treatment	Stone free (%)	Complications (no. of pts)
Denstedt et al. [63]	3	N/A	Basket	100	None
Ulvik et al. [64]	13	N/A	Basket	100	UTI (3), ureteric injury (1), premature contractions (1)
Carringer et al. [65]	4	9	Pulse dye laser	100	None
Scarpa et al. [66]	13	N/A	Ho:YAG, basket, pneumatic	76.9	None
Parulkar et al. [18]	4	N/A	Basket	100	None
Lemos et al. [67]	13	6	Basket, USL	100	None
Lifshitz et al. [68]	4	4	Basket	100	None
Shokeir et al. [69]	8	N/A	Basket, USL	62.5	UTI (1)
Watterson et al. [70]	8	N/A	Ho:YAG	77.7	None
Akpinar et al. [71]	6	8	Ho:YAG	85.7	Pain (1)
Juan et al. [72]	3	N/A	Basket, USL	100	None
Yang et al. [73]	3	N/A	EHL	100	None
Rana et al. [74]	19	11	Lithoclast	79	None
Travassos et al. [75]	9	8	Basket	100	None
Cocuzza et al. [76]	7	8	Ho:YAG, basket	N/A	None
Elgamasy et al. [77]	15	NA	Pneumatic	N/A	Premature labor (1), stent migration (1)
Polat et al. [78]	16	N/A	Pneumatic	72.7	None
Atar et al. [79]	19	8	Ho:YAG, basket	88.2	UTI (1), pain (4)
Hoscan et al. [80]	34	7	Pneumatic	85.3	UTI (3), premature contractions (1)
Isen et al. [81]	12	9	Pneumatic	N/A	None
Johnson et al. [82]	46	7.8	Ho:YAG, basket	88	Preterm labor (2)
Bozkurt et al. [83]	41	9	Pneumatic, Ho:YAG, basket	87.8	Ureteric injury (4), UTI (4), pain (6), sepsis (1)
Abdel-Kader et al. [84]	17	N/A	Pneumatic	100	None
Keshvari et al. [85]	44	N/A	Pneumatic	100	None
Wang et al. [86]	64	8	Ho:YAG	81.2	Premature contractions (1)
Adanur et al. [87]	19	9	Ho:YAG	N/A	Premature contractions (1), UTI (1), migrated stent (1)
Teleb et al. [88]	21	N/A	Pneumatic	N/A	UTI (2)
Zhang et al. [89]	117	N/A	Ho:YAG	87.5	Premature contractions (12), sepsis (1)
Tan et al. [90]	23	N/A	Ho:YAG	87	UTI (1)