Management of Urolithiasis in Pregnancy

65
Management of Urolithiasis in Pregnancy

Husain Alenezi¹ & John D. Denstedt²

¹ Urology Unit, Department of Surgery, Sabah Al‐Ahmad Urology Center and Al‐Adan Hospital, Kuwait

² Division of Urology, Department of Surgery, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada

Anatomic changes during pregnancy

Pregnancy induces a number of anatomic changes within the urinary tract. Renal size increases secondary to an increase in renal vascular volume and an increase in the renal interstitial space. Hydronephrosis of varying severity is experienced by approximately 90% of pregnant women by the third trimester. The hydroureter extends to the sacral promontory and is typically absent more distally. The hydroureteronephrosis of pregnancy results primarily from compression of the gravid uterus [1]. Physiologic hydronephrosis can affect 90% of right kidneys and up to 67% of left kidneys [2]. The hydroureter is more prevalent and severe on the right side, secondary to uterine dextrorotation, as well as a pressure‐reducing effect of the sigmoid colon on the left side. The ureteric smooth muscle relaxation due to increased levels of progesterone has also been implicated in the development of gestational hydronephrosis [3, 4]. However, this mechanism may contribute to the early development of hydronephrosis, between 6 and 10 weeks of gestation, while the mechanical factor remains the major cause thereafter. Support for a primarily mechanical theory includes absence of urinary tract gestational ureteral dilation below the pelvic brim in patients with a pelvic kidney and in those who have undergone previous urinary diversion. The bladder is displaced anterosuperiorly by the gravid uterus, bladder capacity increases, and the detrusor muscle becomes relatively hypotonic and has decreased sensation (Table 65.1). The urothelium becomes congested and hyperemic.

Table 65.1 Anatomic changes in the genitourinary tract during pregnancy.

System	Anatomic changes
Kidney	Renomegaly Hydronephrosis
Ureter	Hydroureter
Bladder	Anterosuperior displacement Increased capacity
Urethra	Urothelial hyperemia and congestion Squamous metaplasia

Physiologic changes during pregnancy

Pregnancy induces physiologic changes in many organ systems, including the renal system (Table 65.2). Glomerular filtration rate (GFR) and renal plasma flow increase by 40–65% and 50–85%, respectively [5], secondary to an increase in the cardiac output and decrease in the renal vascular resistance. Creatinine clearance increases by up to 50% [6], leading to lower serum creatinine and urea levels, a higher level of filtered glucose and glucosuria, and higher level of urine sodium, calcium, uric acid, citrate, magnesium, and glucosminoglycans. Enhanced renal filtration additionally affects dosing of antibiotics as well as anesthetic agents. Other nonrenal systems undergo physiologic changes as well.

Table 65.2 Physiologic changes during pregnancy.

System	Physiologic changes
Genitourinary
Kidney	↑ Blood flow and vascular volume ↑ Glomerular filtration rate ↑ Proteinurea, uricosuria, calciuria, and citraturia ↓ Serum creatinine and blood urea nitrogen
Bladder	↓ Sensation and relative hypotonia
Cardiovascular	↑ Cardiac output ↑ Heart rate and stroke volume ↑ Blood volume ↓ Systemic vascular resistance ↓ Cardiac output near end of pregnancy ↓ Venous return ↓ Hematocrit
Respiratory	↑ Consumption of oxygen Hypoxemia Hypoventilation ↓ Functional residual capacity
Hematologic	Hypercoagulable state ↑ Factors VII, VIII, and X ↑ Fibrinogen ↓ Fibrinolytic activity
Gastrointestinal	↓ Gastrointestinal motility Relaxation of gastroesophageal sphincter

Mineral metabolism and stone formation during pregnancy

The homeostasis of urolithiasis‐promoting and ‐inhibiting factors is altered in pregnancy. Placental 1,25‐dihydroxycholecalciferol increases intestinal resorption of calcium as well uptake of calcium from bone. The increase in absorbed calcium is offset by an increase in GFR and subsequent increased filtered load of calcium. Parathyroid hormone secretion is decreased, suppressing the tubular resorption of calcium. Thus, serum calcium levels generally remain unchanged and hypercalciuria occurs. Uric acid and oxalate excretion is increased due to increased GFR, and fetal and dietary factors [6–8]. Hypercalciuria, uricosuria, and oxaluria all create a favorable environment for renal calculus formation.

Pregnancy, however, is not associated with an increased incidence of urolithiasis compared to the nonpregnant population [9, 10]. This is most likely explained by the increase in filtered citrate, magnesium, and glycosaminoglycans [6–8], all of which are known inhibitors of crystal aggregation and growth.

Renal calculi during pregnancy are documented to be composed primarily of calcium phosphate (74%) and calcium oxalate (26%) [11].

Calcium supplementation during pregnancy is associated with a reduction in the risk of preeclampsia, maternal morbidity and mortality, and preterm labor [12–14]. There is evidence that calcium supplementation during pregnancy may however be associated with a slight increased risk of urolithiasis [14].

Incidence

The incidence of symptomatic urolithiasis in pregnancy is between 1 in 244 and 1 in 2000 pregnancies [15–17]. The overall incidence of urolithiasis is uncertain, but is estimated to be higher, as some asymptomatic renal calculi may remain undetected. There are no observed differences in the rate of urolithiasis between pregnant and nonpregnant women [18, 19].

The average age of presentation is 27 [20] with 80–90% of cases detected during the second and third trimesters. Urolithiasis seems to be higher in multiparous women, in white patients, and in patients with a history of hypertension and renal disease [20, 21]. Ureteral calculi present twice as often as renal calculi [22, 23]. Up to 30% of patients have a history of stone disease [24].

Presentation

Symptomatic pregnant patients may present with abdominal or flank pain (85–100%), gross (15–30%) or microscopic hematuria (95–100%), lower urinary tract symptoms, urinary tract infection, preeclampsia, and premature labor [25–27]. Nausea and vomiting are invariably present as well. A comprehensive differential diagnosis of abdominal pain during pregnancy is given in Table 65.3.

Table 65.3 Differential diagnosis of acute abdominal pain in pregnancy.

Urologic causes	Gynecologic and obstetric causes	General surgical causes
Urolithiasis Pyelonephritis	Premature labor Placental abruption Chorioamnionitis Ectopic pregnancy Ovarian torsion Pelvic inflammatory disease	Appendicitis Cholecystitis Diverticulitis Intestinal obstruction Gastroenteritis Hernia Pancreatitis Mesenteric lymphadenitis

Acute abdominal or flank pain in pregnancy presents a unique diagnostic challenge. The clinician has to consider anatomic alterations induced by pregnancy that can lead to various conditions mimicking each other. For example, the appendix can be displaced superiorly after the first trimester and appendicitis may mimic pyelonephritis or cholecystitis [28].

Diagnostic tests

Imaging and radiation exposure

Accurate diagnosis of abdominal pain in pregnancy largely depends on diagnostic imaging. The necessity of diagnostic imaging and exposure to ionizing radiation is commonly anxiety‐provoking for both patients and clinicians. Use of the ionizing radiation needs to be avoided whenever possible, due to its potential teratogenic effects. When its use is unavoidable, a detailed discussion with patients is required, carefully explaining the potential risks associated with its use. Application of techniques to reduce radiation dose is mandatory. The delivered dose of radiation should be as low as possible, while maintaining the quality of diagnostic image that is useful for diagnosis. Effects of ionizing radiation on the fetus can be categorized into four classes: intrauterine fetal death, fetal malformation, disturbance of growth and development, and mutagenic/carcinogenic effect [29, 30]. The risk of exposure is also dependent on the dose of the radiation and fetal gestational age [31].

The radiation dose is measured in Gray units (Gy, SI system), representing the amount of ionizing radiation absorbed by tissue. Previously, the radiation dose was measured in rads (1 Gy equating to 100 rads), representing the radiation dose delivered and not necessarily absorbed by the tissues. The delivered fetal dose for each diagnostic imaging procedure varies according to the technique used (Table 65.4) and maternal body configuration. Most diagnostic procedures deliver fetal doses below 50 mGy [32]. This dose of radiation has not been associated with an increase in fetal anomalies or pregnancy loss [33]. The American College of Obstetricians and Gynecologists recommends that “women should be counseled that the X‐ray exposure from a single diagnostic procedure does not result in harmful effects” [33].

Table 65.4 Fetal radiation doses for radiologic tests.

Procedure	Fetal dose (mGy)
CT scan (conventional)	8.0–49
CT scan (limited)	0.244–1.372
IVU	1.7–10
KUB	1.4–4.2
Nuclear renogram (MAG3 or DTPA)	0.2–4.0
MRI	No radiation, no known adverse effects
Ultrasonography	No radiation, no known adverse effects

CT, computed tomography; IVU, intravenous urography; KUB, kidney–ureter–bladder plain film; MAG3, mercaptoacethyltriglycine; DTPA, diethyltriamine penta‐acetic acid; MRI, magnetic resonance imaging.

The effects of radiation depend on the fetal gestational age [31]. Fetal tissues are most susceptible to ionizing radiation during the first trimester when organogenesis is occurring. Use of ionizing radiation should be avoided during this period. The teratogenic effects of radiation are summarized in Table 65.5. In addition, ionizing radiation has a potential to induce development of childhood cancers such as leukemia. Historic studies raised concern that in utero radiation exposure may increase the incidence of childhood malignancy by 1.3–2 times [31, 34]. However, more recent investigations have reputed this evidence [35]. The National Radiological Radiation Board concluded that the majority of diagnostic radiologic procedures performed in an individual pregnancy presents no substantial risk and carries a less than 1 in 5000 chance of developing a fatal childhood cancer (1 in 33 000 per mGy). Additionally, the risk is less than 1 in 10 000 for development of induced inheritable disease (1 in 40 000 per mGy) [36, 37].

Table 65.5 Effects of significant radiation exposure on the fetus.

Gestational age (weeks)	Radiation effect
2–4	All lethal or no impact on fetus, without any malformations present
4–10 (organogenesis)	Microcephaly, growth retardation, gross malformations
10–17 (peak neurologic development)	Microcephaly, mental retardation, growth retardation and sterility in adult life
17–40	Adverse effects seen rarely, if ever

Ultrasound

Ultrasonography (Figure 65.1) is the most useful initial test when acute abdominal or flank pain in pregnancy is investigated. The appeal of ultrasound derives from the lack of ionizing radiation and absence of harmful effects, documented over many years of use. Ultrasonography can effectively evaluate the renal parenchyma, pelvicalyceal system, and dilated ureter, and to some extent visualize renal and ureteral calculi.

Image described by caption. — **Figure 65.1** Ultrasound images. (a) Bladder (Doppler) demonstrating an absence of left ureteric jet, in a 30 year‐old pregnant woman, G1P1 GA 30 weeks. (b) Kidney with a right renal stone in a 31 year‐old pregnant woman, G2P2 GA 28 weeks.

The accuracy of ultrasonography in the detection of renal calculi is reported to be between 34 and 86% [20–22]. This wide variation in the reported accuracy most likely derives from the fact that ultrasound is operator‐dependent. Additionally, ultrasonography is very nonspecific and often cannot distinguish between hydronephrosis of pregnancy and that secondary to calculi.

Several modifications to ultrasonography have attempted to improve its accuracy. Transvaginal ultrasound was demonstrated to be effective in the detection of distal ureteral calculi [38]. Detection of hydroureter below the pelvic brim, with any ultrasound approach, may alert the operator to the presence of distal ureteral calculi [39]. The presence of ureteral jets on ultrasound or Doppler ultrasound can exclude complete ureteral obstruction in 80–100% of cases [40].

Resistive index (RI) measurements may increase the accuracy of ultrasonogarphy in distinguishing between the physiologic dilation and calculus‐related obstruction [41]. An RI of 0.70 was demonstrated to have 87% accuracy, 45% sensitivity, and 91% specificity for diagnosis [41, 42]. Additionally, a difference in RI values (ΔRI) between the affected side and the normal contralateral kidney of 0.06 increases the sensitivity of ultrasonography to 95%, with specificity of 100% and accuracy of 100% [42]. This type of ultrasonography adjunct was demonstrated to be limited by pre‐existing renal disease, nonsteroidal anti‐inflammatory drugs (NSAIDs) and acute onset of obstruction (<6 hours).

Intravenous urography

Intravenous urography (IVU) (Figure 65.2) is effective in describing anatomy and function of the collecting system, along with the site and degree of potential obstruction. IVU can be considered as a second‐line investigation for hydronephrosis of pregnancy. Small published series report relatively high specificity in diagnosing renal calculi in pregnancy [20, 43]. If needed, a limited three‐shot protocol should be used: a scout film, 15–20 minute film, and a selected delayed image at 2 hours. Fetal shielding should be used at all times [44].

Image described by caption and surrounding text. — **Figure 65.2** (a, b) Kidneys, ureters, and bladder intravenous urogram demonstrating a right ureteral calculus in a 30 year‐old pregnant woman, G1P0 GA 29 weeks.

IVU, if considered, should be used judiciously due to potential risks of intravenous contrast and fetal radiation exposure. Intravenous contrast was demonstrated to cross the placenta in small quantities, but without any described teratogenic effects [45]. However, exposure to iodinated intravenous contrast during late pregnancy can lead to fetal thyroid suppression, and requires screening for neonatal hypothyroidism [45].

A limited IVU delivers 0.5 mGy of radiation to the fetus, which is below the 5 mGy safety point. Fetal shielding and films obtained in a prone position can further reduce the dose.

Computed tomography

A traditional computed tomography (CT) scan (Figure 65.3) remains contraindicated in pregnancy due to the high dose of ionizing radiation delivered. Recently, however, a low‐dose CT scan protocol has been described for the detection of renal calculi during pregnancy. A low‐dose CT scan protocol uses a pitch of 1.5 (from 0.75 in regular CT), 120 kV, and a mean of 109 mA. With these modifications the mean delivered fetal radiation exposure is 705.5 mrad (range 244–1372 mrad), although this is probably an overestimate due to maternal changes in body geometry. Obese patients receive a higher estimated dose on average. The resulting CT images are of much lower quality in comparison to traditional scans, but this investigation still provides high sensitivity and specificity for detection of renal and ureteral calculi.