AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Urolithiasis is the most common cause of nonobstetrical abdominal pain that requires hospitalization among pregnant patients.^{1, 2} The relative incidence and rate of recurrence of calculi in pregnant patients (1 per 1500 pregnant patients) is similar to that of nonpregnant patients.³ Symptomatic stones are found in the ureter twice as often as in the renal pelvis and affect both ureters in equal frequency. Eighty to ninety percent are diagnosed after the first trimester.^{4, 5}

Urolithiasis in pregnancy is often a diagnostic and therapeutic challenge for multiple reasons. First, potential adverse effects of anesthesia, radiation, and surgery often complicate traditional diagnostic and treatment modalities. Second, many signs and symptoms of urolithiasis can be found in a normal pregnancy or may be associated with broad differential diagnoses of other sources of abdominal pathologic conditions. Appendicitis, diverticulitis, or placental abruption was diagnosed inaccurately in 28% of patients in a 1992 study by Stothers and Lee. Finally, most stones (64-84%) pass spontaneously with conservative treatment.^{6, 7} However, if the calculus does not pass, it may initiate premature labor, produce intractable pain in the patient, cause urosepsis in the setting of a urinary tract infection, or interfere with the progression of normal labor.

Of the various imaging modalities currently available, renal ultrasonography has become the first-line screening test, while limited intravenous pyelography (IVP) or CT scanning is reserved for more complex cases. Ideally, no ionizing radiation is used in the first or second trimesters, if at all possible. MRI has limited utility in urinary stone disease, and nuclear renography is reserved for functional studies to direct treatment. These are of limited value during pregnancy.

Treatment of stones in pregnancy ranges from conservative management (eg, bed rest, hydration, analgesia) to more invasive measures (eg, stent placement, ureteroscopy with stone manipulation, percutaneous nephrostomy). With appropriate diagnosis and management, the outcome for both the mother and baby is excellent.

Prophylaxis

Prevention is the best cure, and multiple investigators have suggested prophylactic measures to prevent the difficult course of treating urolithiasis in pregnancy. Denstedt and Razvi (1992) suggest prophylactic treatment of asymptomatic caliceal stones in women of childbearing age who are planning pregnancies.⁸ Biyani and Joyce (2002) recommend metabolic evaluation in known stone formers, as well as prophylactic treatment of asymptomatic stones prior to pregnancy.⁴ In support of their recommendation, they sited Glowacki et al (1992), whose study monitored 107 asymptomatic patients with renal calculi over 31.6 months. They found that 31.8% became symptomatic over that period.⁹

Women with cystinuria who desire pregnancy should seek genetic counseling, and management of their disease should begin prior to pregnancy.¹⁰

Pathophysiology

Although pregnancy-induced urinary stasis and hypercalcemia of pregnancy have been proposed as likely etiologic factors in urolithiasis, this has been disputed. Pregnancy-related events that tend to enhance stone formation include decreased ureteral peristalsis, physiological hydronephrosis, infection, and increased urinary calcium excretion. Augmented excretion of urolithiasis inhibitors, such as citrate, magnesium, and glycosaminoglycans, neutralize these phenomena in pregnant patients, who are no more likely to form urinary calculi than nonpregnant patients.⁸ Coincident to the increased hypercalciuria in pregnancy is an increase in total circulating blood volume, making the relative supersaturation of calcium insignificant.

Anatomic and physiologic changes during pregnancy

Hydroureteronephrosis is the most significant renal alteration during pregnancy. Physiologic dilatation of the collecting system begins in the first trimester at 6-10 weeks' gestation and persists until 4-6 weeks following delivery.⁵ Early theories suggest that hydronephrosis of pregnancy may be a hormonally induced phenomenon whereby ureteral smooth muscles relax in response to high levels of circulating progesterone. In early pregnancy, increased progesterone secretion dilates the ureters and reduces ureteral peristalsis, causing hydronephrosis. Alternatively, the predominant theory ascribes ureteric dilatation to compression of the ureter by the enlarging gravid uterus at the level of the pelvic brim, where the ureter crosses the iliac vessels.

Dilation is greater on the right side than on the left because of pressure due to physiologic engorgement of the right ovarian vein and dextrorotation of the uterus.⁴ Swanson and associates (1995) observed that hydroureteronephrosis was not routinely found below the pelvic brim and was altogether absent in patients who had undergone a urinary diversion.⁵

Volume changes during pregnancy

Glomerular filtration rate (GFR) and renal plasma flow (RPF) increase by as much as 25-50% during pregnancy. Both of these changes are attributable to increases in cardiac output, decreases in renal vascular resistance, and increases in serum levels of progesterone, aldosterone, deoxycorticosterone, placental lactogen, and chorionic gonadotropin. GFR and RPF enhancements also contribute to the increase in glucose, amino acid, protein, and vitamin secretion. As a result of the GFR and RPF modulations, which peak at 9-11 weeks' gestation, renal volume increases during pregnancy by as much as 30% above the reference range. The sustained elevation of prolactin in the pregnant patient has a growth hormone–type effect by increasing the glomerular surface area, which also contributes to an increase in renal volume.

Along with increases in GFR and RPF, the filtered load of sodium, calcium, and urate increases. Although calcium and urate excretion increases, sodium excretion remains unchanged. The urinary excretion rate of calcium stone inhibitors, such as citrate and magnesium, also increases in the pregnant patient; likewise, increased glycosaminoglycans and acidic glycoproteins inhibit oxalate stone formation (eg, nephrocalcin). This explains why pregnancy is not associated with a net increase in the rate of stone formation relative to nonpregnant patients. The net effect of these physiologic changes is a stable relative supersaturation of important ions such as calcium oxalate, urate, and phosphate.

Uric acid stone formation

The formation of uric acid stones requires continued and excessive oversaturation of urine with uric acid or extreme aciduria. Dehydration, hyperuricosuria, and very acidic urine contribute to uric acid supersaturation and stone formation. However, during gestation, urine tends to be more alkaline, probably because of greater intrinsic purine use and increased urinary citrate excretion. Thus, renal units are generally protected against uric acid stone formation during pregnancy.

Calcium oxalate and calcium phosphate stone formation

Although pathologic calcium oxalate supersaturation has been identified in the urine of pregnant women, the incidence of crystalluria is no higher than in women who are not pregnant. In the pregnant patient, physiologic absorptive hypercalciuria occurs from an elevation of serum 1,25 dihydroxycholecalciferol (1,25 vitamin D). This hormone, which is secreted by the placenta, augments calcium absorption in the GI tract and suppresses parathormone production, which results in an increased renal excretion of calcium. Additionally, dietary supplementation of calcium during gestation further augments calcium excretion. Some reports suggest that calcium excretion increases 200-300% compared to that of healthy patients who are not pregnant. However, increased concentration of the aforementioned urolithiasis inhibitors present in urine during gestation and increased urine fluid output counters the increased risk imposed by any hypercalciuria.

Struvite stones

Struvite stones only form when the urinary tract is infected with urea-splitting organisms (eg, Proteus species). These infected stones are usually composed of pure magnesium ammonium phosphate but may be formed around a coexisting calcium, uric acid, or cystine stone. Struvite stones appear to develop more commonly when a congenital abnormality of the collecting system is present.

Frequency

United States

The reported incidence of urinary calculi in pregnant women is around 1 per 1500 pregnant women, which is similar to that of nonpregnant patients.³

Approximately 80-90% of pregnant patients with urinary calculi present with symptoms during the second or third trimester because spontaneous stone passage is more difficult at this stage of pregnancy.

Ureteral stones occur twice as often as kidney stones in pregnant patients.

Approximately 64-84% of renal calculi pass spontaneously with conservative management,^{6, 7} especially if they 4 mm or smaller. Stones that are 7 mm or larger are much less likely to pass without intervention and often require some type of treatment.

Mortality/Morbidity

Urolithiasis associated with ureteral obstruction and upper tract infection mandates immediate treatment; this is a true urologic emergency that can potentially lead to urosepsis, perinephric abscess formation, or even death in pregnant women. Urolithiasis in a pregnant patient may initiate premature labor or interfere with the progression of normal labor, which poses a significant health risk to the fetus.

Race

Hispanic people and white people are most commonly predisposed to urinary calculi. Black people are less predisposed to kidney stone formation. The exact cause of this discrepancy is not known, but dietary influences may play a role. When calculi are present, black people have a higher incidence of infected urinary stones than white people.

Sex

The reported incidence of urolithiasis is higher in men, with a male-to-female ratio of 3:1, although this ratio is decreasing, possibly related to dietary or obesity trends in the United States.

Age

Urinary stones in women usually manifest during the third to fifth decades of life, with an average age of 24.6 years. Urolithiasis occurs in pregnant women at rates similar to age-matched nonpregnant women.⁵

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

Urolithiasis is derived from the Greek words ouron (urine) and lithos (stone). When in the setting of pregnancy, urolithiasis presents as a diagnostic challenge. Clinical manifestations of urolithiasis in pregnant patients often resemble signs and symptoms of pregnant patients without stones, not to mention many other sources of abdominal pathologic conditions (see Differentials).

Flank pain (89%) and hematuria (95%) are the most common symptoms of kidney stones⁷; however, these findings may also represent physiologic changes of pregnancy. Pregnancy-induced hydronephrosis can cause flank pain and even mimic renal colic,¹¹ and microanatomic alterations in venous fragility of the collecting tubules may cause hematuria.¹² Aside from its presentation in normal conditions, hematuria without discomfort is rare when a calculus is present.⁵

Alternatively, pregnant patients with ureteral stones may report pain in atypical locations or the pain of premature labor. Often, signs of premature labor, ectopic pregnancy, or complicated labor may mimic clinical symptoms of renal-ureteral calculi. Therefore, maintaining a high degree of suspicion in all pregnant women with abdominal or pelvic pain, hematuria (gross or microscopic), or unresolved urinary tract infections is imperative.

• The most common symptoms of urolithiasis of pregnancy include the following:
• • Flank pain
  • Pain radiating to the groin or labia
  • Nausea
  • Dysuria
  • Gross hematuria
• Less common symptoms of urolithiasis include the following:
• • Lower abdominal pain
  • Fever/chills
  • Vomiting
• Other important historical findings pertinent to urolithiasis include the following:
• • Recurrent or persistent urinary tract infection (especially during the current pregnancy)
  • History of previous calculi, either in a previous pregnancy or in the nonpregnant state
  • Prior urologic surgery
  • History of prior complicated pregnancy or premature delivery
• Sites of urolithiasis may be localized based on the patient's description of pain.
• • Urolithiasis that obstructs at the ureteropelvic junction generally manifests as deep flank pain without radiation to the groin.
  • Urolithiasis within the mid portion of the ureter can cause severe and intermittent pain, pain in the flank, and ipsilateral lower abdomen pain with radiation to the vulvar area.
  • Urolithiasis in the distal ureter or ureterovesical junction may manifest as pain that radiates to the labia and irritative voiding symptoms such as urinary frequency and dysuria.

Physical

• Patients with renal colic are often extremely restless, exhibiting active movement on presentation.
• On inspection, the abdomen may be moderately distended, especially if the patient has coexisting ileus.
• On palpation, the abdomen is soft and tender in the upper quadrant. This is significantly different from the motionless presentation and rigid abdomen of a patient with peritonitis.
• On auscultation, bowel sounds do not provide helpful clues because they may range from hyperactive to markedly diminished because the patient may have concurrent ileus.
• Other signs and symptoms include costovertebral angle tenderness, generalized flank tenderness, and voluntary guarding of the abdominal musculature.

Causes

Stone formation during pregnancy does not appear to have any etiologic factors that are unique to pregnancy. Risk factors associated with urolithiasis in general include the following:

• Heredity
• Age (third to fifth decades of life)
• Decreased water intake
• Increased environmental temperature and/or dry climate
• Diet (eg, high in calcium, sodium, and red meat consumption)
• Occupation (eg, exposure to hot climate)
• Geographic location (eg, southwest United States ["stone belt"])
• Social class (related to occupation and diet)
• Excessive weight or obesity (apparently a risk factor only for women and not for men)

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Spontaneous renal rupture during pregnancy¹³
Foreign body obstruction
Small bowel obstruction
Large bowel obstruction

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Urinalysis - To assess for microscopic hematuria
• • The presence of red blood cells may suggest the presence of a calculus.
  • Microscopic hematuria is present in 95% of patients with urinary stones when both dipstick and microscopic analysis are used.
  • Pyuria, which can result from an inflammatory reaction to a stone or infection, mandates evaluation of a coexisting urinary tract infection. Urinary tract infection is present in approximately 31%.⁷
  • Urine pH greater than 7 may signal the presence of infected stones (magnesium-ammonium-phosphate) with urea-splitting organisms (eg, Proteus and Klebsiella species).
  • Acidic urine (pH <5) suggests the presence of a uric acid stone.
• Urine culture - To identify the offending bacteria and determine antibiotic sensitivities
• Complete blood cell (CBC) count - To determine the presence or absence of systemic infection
• Renal panel (serum chemistries)
• • A decrease in serum bicarbonate and potassium levels suggests an underlying renal tubular acidosis that may cause the formation of calcium phosphate stones. An increase in the serum calcium level might suggest possible primary or secondary hyperparathyroidism. Hyperuricemia suggests possible gouty diathesis and hyperuricosuria, which can increase the risk for both uric acid and calcium stone formation.
  • Elevated serum creatinine levels suggest azotemia due to ureteral obstruction or chronic renal insufficiency. The physiologic increase in GFR during pregnancy dictates that the serum creatinine and BUN levels should be nearly 25% less than levels in the nonpregnant patient.¹⁴
• Metabolic stone prevention studies (ie, 24-hour urine collection)
• • For patients with a sincere interest in reducing their risk of developing more urinary stones, a 24-hour urine collection for stone prevention analysis is recommended. However, because of the physiologic and electrolytic changes associated with pregnancy, metabolic studies should be postponed until completion of pregnancy. Patients undergoing metabolic analysis studies should be willing to make long-term changes in their diet or lifestyle and take medications and/or supplements to help reduce their risk of new stone formation.
  • The metabolic evaluation should include, as a minimum, a 24-hour urine collection and determination of total volume and sodium, oxalate, citrate, uric acid, calcium, phosphate, and magnesium. Various commercial programs are available from laboratories such as Mission Pharmacal, LabCorp, Litholink, Dianon Systems, Nichols, and UroCor. All of these provide accurate and reliable results from the 24-hour urine collections. The cornerstone of the metabolic evaluation is the stone analysis. All patients should be encouraged to strain urine until the stone passes or repeat imaging is performed.

Imaging Studies

• Radiologic diagnosis of urolithiasis in pregnant patients is complicated by the physiologic and hemodynamic changes of pregnancy such as increased renal blood flow (RBF) and GFR, in addition to the concern for fetal radiation exposure. Delay in diagnosis or inappropriate therapy may risk maternal renal damage, premature labor, spontaneous abortion, pyonephrosis, and/or maternal hypertension. Tailor the diagnostic evaluation and management of the gravid patient to the individual.
• Historically, the diagnosis of urolithiasis in women who are nulliparous entailed using IVP. Recently, IVP has been replaced by nonenhanced CT scan as a screening test for urolithiasis. However, in equivocal cases, IVP remains the definitive standard. In pregnant women, standard IVP and CT scans pose significant radiation exposure to the fetus, especially the CT scan because of its higher radiation exposure. Despite the fact that the radiation dose provided by a standard IVP is 25 times lower than the threshold exposure for risk (1-3%) of congenital malformations, the risk to the fetus is real. Thus, standard IVP and, particularly, CT scans are discouraged in the first and second trimesters in pregnant women. Swanson and associates (1995) calculated radiation exposures of diagnostic studies used for urolithiasis in pregnancy, as follows:⁵
• • Radiography of the kidney, ureters, and bladder (KUB) - 0.05 cGy
  • Limited IVP (3 films) - 0.2 cGy
  • Pelvic CT scanning - 2.2 cGy
• Renal ultrasonography, with or without Doppler studies, is recommended as the primary imaging modality in pregnant women. In the event that ultrasonography findings are equivocal and clinical symptoms strongly suggest renal calculi, a limited IVP with reduced films and radiation exposure may be performed. If the ultrasonography and limited IVP test findings are unclear, additional tests or procedures may be indicated, depending on the clinical scenario. However, when indicated, many suggest proceeding directly to ureteroscopy for diagnosis and treatment, especially in the first and second trimesters.^{15, 16, 17} Radiation exposure in the third trimester is less of a risk to the fetus.
• Renal ultrasonography
• • Renal ultrasonography is the first-line screening tool for urolithiasis in pregnant patients. Stothers and Lee (1992) found that renal ultrasonography provided a sensitivity of 34% and specificity of 86%,⁷ yet Parulkar et al (1998) reported 95% and 87%,⁶ respectively. The sonogram may not actually show the stone.
  • However, false-positive results may occur in the setting of extrarenal pelvis, vesicoureteral reflux, a high urine-flow rate, parapelvic cysts, and crossing vessels within the renal sinus. Up to 35% of patients with documented acute ureteral obstruction may not demonstrate any significant hydronephrosis, which makes standard ultrasonography less useful. Furthermore, differentiating hydronephrosis caused by an obstructing calculus due to physiologic dilation of pregnancy may be difficult.
  • Advantages of renal ultrasonography include avoidance of radiation exposure to the fetus, no pain, avoidance of proallergenic intravenous contrast material, and the ability to examine coexisting abdominal or pelvic disease etiologies.
• Vaginal ultrasonography: This has been found valuable in revealing stones in the distal ureter that are not visualized with renal ultrasonography. Laing et al (1994) reported that distal ureteral stones were identified in 13 of 13 patients; renal ultrasonography revealed the distal stones in only 15% of the 13 patients. Laing et al also observed that patients tolerated the procedure well.¹⁸ Loughlin and Ker (2002) endorse the use of a transrectal ultrasonography probe if a vaginal transducer is unavailable.¹⁹
• Renal ultrasonography with Doppler sonography
• • In contrast to standard renal ultrasonography, ultrasonography with Doppler studies enables recording of waveform tracings of the renal vasculature. Ureteric obstruction causes an increase in renal vascular resistance, resulting in a reduction of diastolic blood flow and a rise in renal resistance. Based on waveform tracings, a resistive index (RI) value is calculated (RI = peak systolic velocity - peak diastolic velocity / peak systolic velocity), providing improved sensitivity and specificity for differentiating obstructed from nonobstructed dilated collecting systems. An elevated RI value of greater than 0.70 is specific for ureteral obstruction. Alternatively, a difference in the RI of 0.04 or more between the affected and contralateral kidney also suggests an obstruction in the side with the higher RI value.
  • Shokeir and Abdulmaaboud (1999) also evaluated the change in RI, which showed increased sensitivity (88%) and specificity (98%) in diagnosing ureteral obstruction.²⁰
  • Color Doppler renal sonography is a new addition to sonographic visualization of calculi, with a reported sensitivity of 100% and a specificity of 91% for diagnosing ureteral obstruction. This important study demonstrates the presence of ureteral jets (streams of densely opacified urine) flowing into the bladder (containing dilute nonopacified urine). The absence of these jets may suggest ureteral obstruction, while symmetric jets indicate the absence of obstruction. In addition, color Doppler studies also aid in differentiating iliac vessels from a dilated ureter.
  • Equivocal sonographic results that do not suggest either physiologic hydronephrosis of pregnancy or urolithiasis require further imaging with limited excretory urography.
  • Disadvantages of renal sonography include the following:
  • • Suboptimal determination of the level of obstruction
    • Difficulty in showing the ureters and intraureteral calculi
    • Possible difficulty differentiating physiologic hydronephrosis of pregnancy from acute obstructive hydronephrosis
    • Unable (in most cases) to determine the size or shape of the urinary calculi
    • Difficulty visualizing calculi obscured by overlying bony structures, fetal skeleton, or fecal material
    • Operator dependent
  • Disadvantages of renal sonography with color Doppler include the following:
  • • Relies on elevated urine output and density differences between urine in the bladder and urine existing within the ureter
    • Degree of asymmetry of the ureteral jets unaltered from reference range because of calculi causing low-grade or no obstruction
    • Operator dependent
  • Normal findings on renal sonography are consistent with the following results:
  • • Degree of renal and ureteral dilation consistent with pregnancy
    • RI value of less than 0.70 in both kidneys
    • Symmetric ureteral jets
    • No specific calculus identified
  • High probability of urolithiasis during pregnancy exists with the following results:
  • • Greater degree of dilatation disproportionate to hydronephrosis of pregnancy in collecting system
    • RI value greater than 0.70 in the symptomatic kidney or change in RI greater than 0.60²⁰
    • Dilated ureter extending below the level of the iliac arteries
    • Asymmetry of ureteral jets
    • Identification of calculus
• Excretory urography
• • Excretory urography remains an important diagnostic modality for stone detection in nonpregnant women, allowing the investigator to accomplish the following:
  • • Establish the presence of an obstruction
    • Locate and determine the size of the offending calculus
    • Estimate renal function
    • Identify anatomic abnormalities that may alter the treatment algorithm
    • Detect altered renal physiology secondary to obstruction
  • Intravenous urography (IVU) or IVP consists of initial abdominal radiography of the KUB followed by a second radiograph obtained 20-30 minutes after the intravenous injection of a contrast medium. The initial KUB radiograph exposes the fetus to 0.002 Gy; however, because the standard IVU necessitates 4 or 5 films, the patient may be exposed to a total of 0.004-.010 Gy. The dose of radiation during IVU has been reported to be safe to the fetus during the second and third trimesters. Limited IVP, however, has been shown to successfully reveal calculi without the high radiation dose of full IVP. Stothers and Lee (1992) recommend a scout film, a 30-second film, and a 20-minute film. They report successful visualization of 16 of 17 stones in pregnant patients who presented with acute renal colic.⁷
  • Indications for excretory urography in a pregnant patient may include the following:
  • • Sonography results that are equivocal for pregnancy dilatation or urolithiasis
    • Azotemia suggestive of postrenal obstruction
    • Persistent fever or persistent positive finding on urine culture despite 48 hours of parenteral antibiotic treatment
    • Massive hydronephrosis on abdominal ultrasonography
  • Disadvantages of IVU include the following:
  • • Risk of IV contrast allergy in the mother and fetus
    • Risk of radiation exposure to the mother and fetus
    • Possible ambiguous differentiation between delayed excretion of contrast material from calculus obstruction and pathologic hydronephrosis, especially in the third trimester
    • Small ureteral calculi obscured by enlarged uterus during IVU studies, especially in the third trimester
• MRI
• • MRI provides quality images of the kidneys and urinary tract with obstruction and is used by some as second line to ultrasonography. It visualizes stones poorly and is therefore rarely indicated.
  • Using T2-weighted imaging, MRI urography can be used to differentiate a physiological upper tract dilatation from a pathologic ureterohydronephrosis during pregnancy and to ascertain whether the obstruction is intrinsic or extrinsic.
  • MRI does not use ionizing radiation or iodinated contrast, but its use during the first trimester is not recommended because the effect of MRI on fetal development is not clear.
  • MRI is expensive, uncomfortable for the pregnant patient, and often unavailable, which further limit its use for urolithiasis evaluation. In addition, it cannot demonstrate the actual stone, only the point of obstruction.
• Nuclear renal scan
• • Nuclear renal scan using technetium Tc 99m diethylenetriaminepentaacetic acid (DTPA) is an excellent study for objectively establishing the differential renal function and the efficiency of drainage of the dilated collecting system (washout times). DTPA is cleared almost exclusively by glomerular filtration. The rate of clearance provides an excellent estimate of GFR. However, nuclear studies do not allow visualization of stones and provide very limited illustration of anatomy. Differing opinions exist on its utility in the diagnosis of urolithiasis in pregnancy.^{4, 14}
  • Drainage half-time of greater than or equal to 20 minutes indicates obstruction, whereas drainage half-time of less than or equal to 10 minutes indicates nonobstruction.
  • Washout or drainage half-times of 10-20 minutes are considered indeterminate.
• Unenhanced helical CT scan: This is reported to be highly sensitive (96-97%) and specific (96-99%) in the diagnosis of ureteric calculi and is effective in differentiating calculi from tumors or blood clots. However, the radiation dose of CT scans can be quite high, substantially exceeding the dosage of a standard IVP, for example. This makes CT imaging less suitable for use during pregnancy, particularly during the first and second trimesters.

Procedures

• Ureteroscopy
• • Ureteroscopy has emerged as a safe and efficient way to treat urolithiasis during pregnancy.¹⁵ Ulvik and associates (1995) have used ureteroscopy to successfully treat urolithiasis and consider it as a diagnostic procedure in difficult cases.¹⁷ Either rigid or flexible ureteroscopes may be used, but Ulvik et al feel that flexible scopes may be better suited in diagnosis during pregnancy.
  • Rittenberg and Bagley reported the use of ureteroscopy for diagnosis with local anesthesia alone in 1988.²¹ Currently available ureteroscopes are small and may be used with minimal or no anesthesia.^{15, 22} Lemos and coworkers (2002) feel that ureteroscopy used solely for diagnosis may be aggressive but agree that it can be used as a single modality for diagnosis and removal of ureteral calculi in pregnancy.¹⁶ Ureteroscopy offers clear-cut diagnosis, with direct visualization, as well as definitive therapy in the same encounter.
• Retrograde pyelography: This can successfully reveal ureteral stones in cases with ambiguous sonography and IVU results. However, this study is performed only during stent placement because of the invasiveness of the examination, possible introduction of bacteria and risk of sepsis, and the need for radiation, sedation, and cystoscopy. Routine retrograde pyelography is not recommended for documentation of ureteral calculi in pregnant patients.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

Conservative measures should be undertaken as the initial management of urolithiasis in pregnancy. The use of intravenous hydration and analgesia has been shown to result in spontaneous passage of symptomatic calculi in 64-84% of patients.^{6, 7} Bed rest, antiemetics, and antibiotics are also important, when indicated.

Some stones may simply become asymptomatic, allowing delay of further treatment. Symptomatic urolithiasis is more likely to resolve when calculi are located in the renal pelvis as opposed to the distal ureter.²³

Treatment goals for the remaining patients are to reduce maternal discomfort, to prevent renal damage and sepsis due to obstructing calculi, and to minimize risks to the fetus. If conservative measures fail to relieve clinical symptoms or to pass calculi, appropriate surgical intervention should be undertaken.

• Urine should be strained to obtain stones when they are passed. Chemical analysis should then be performed to guide postpartum treatment and diet modifications to prevent future stone formation. However, because of the physiologic and electrolytic changes associated with pregnancy, metabolic studies should be postponed until completion of pregnancy.
• Several narcotics have been tested for use during pregnancy. Morphine sulfate, hydromorphone, butorphanol, meperidine, and acetaminophen provide temporary symptomatic relief without harming the fetus. However, avoid codeine during pregnancy because of its association with fetal defects. Long-term use of narcotics in pregnancy can lead to fetal narcotic addiction and even intrauterine growth retardation (IUGR) or premature labor.²⁴
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are also contraindicated because of an increased risk of miscarriage when used in the first trimester. In addition, fetal renal anomalies, fetal pulmonary hypertension, and premature closure of the ductus arteriosus are risks when NSAIDS are prescribed close to term.
• In calcium stone disease, medical management for reduction of calcium stone disease is contraindicated.
• • Thiazide diuretics, which markedly reduce calciuria and resultant stone formation, are a viable treatment option for urolithiasis in the general population. However, thiazide diuretics are contraindicated during pregnancy because they may induce fetal thrombocytopenia, hypoglycemia, and hyponatremia. Additionally, diuretics are generally dangerous because they may interfere with the normal extracellular volume expansion of pregnancy.
  • The safest method of medically managing calcium stone disease during pregnancy is to increase fluid intake and to avoid excessive calcium intake (including calcium-fortified prenatal vitamins). Typically, calcium intake should not exceed 1000-1200 mg/d during pregnancy. This treatment may prevent or reduce the risk of urolithiasis during pregnancy. Sodium intake and protein consumption should also be curtailed.
• In uric acid stone disease, xanthine oxidase inhibitors (eg, allopurinol) prevent uric acid stone formation by inhibiting the final step in human purine metabolism, thereby decreasing both serum and urinary uric acid levels. However, use of xanthine oxidase inhibitors is contraindicated during pregnancy because the effects of the drug on the fetus are unknown. Alternative treatment modalities for uric acid stones during pregnancy include increasing fluid intake, limiting dietary purine intake, and urinary alkalinization.
• Patients with cystine stone disease often have known cystinuria prior to conception. Despite contraindications to the use of common drug therapy, research has shown that careful medical management can allow women with cystinuria who form stones to safely undergo pregnancy without increased risk.
• • Penicillamine reduces cystine stone formation by interchanging disulfide bonds with cystine residues, thereby separating cystine-cystine bonds and allowing increased cystine solubility. Severe or serious adverse effects occur in about 50% of patients. Because this drug has been reported to cause fetal abnormalities in rats, it is contraindicated during pregnancy.
  • Increasing urinary volume to 3,000 cc and urine alkalinization to an optimal urinary pH of around 7.5 are alternative means to treat cystinuria during pregnancy. However, patients with high urinary excretion of cystine (ie, >300 mg/24h) may need low-dose penicillamine treatment. Studies performed by Gregory and Mansell (1983) suggest that the risk of recurrent stone formation may outweigh the theoretical risks of penicillamine exposure in this particular situation.¹⁰
  • Alpha-mercaptopropionyl glycine (alpha-MPG) is an alternative to penicillamine. It has the same mechanism of action and is roughly equal in efficacy with somewhat fewer and milder adverse effects. Like penicillamine, it is contraindicated in pregnancy.

Surgical Care

Surgical intervention may be required in 20-30% of pregnancies complicated by urolithiasis.⁴ Surgical treatments are somewhat limited to providing temporizing drainage of an obstructed system with placement of a ureteral stent or percutaneous nephrostomy, to delay treatment until completion of the pregnancy, or to definitively diagnose and treat the stone with ureteroscopic methods.

A broad spectrum of interventions, ranging from ureteral stent placement to open lithotomy, have been used to successfully treat urolithiasis in pregnancy⁸; however, regardless of the mode or invasiveness of the surgical intervention (eg, endoscopic, percutaneous, open), each carries an element of risk to the mother and fetus. Thus, surgical intervention is reserved for pregnant patients in whom conservative management fails or when surgery is otherwise indicated. Admission of these patients by the OB service for consultation with a urologist is not unusual. As a result, most if not all, of these women undergo noninvasive fetal monitoring.

• Indications for surgical intervention include the following:
• • Ureteral obstruction associated with increasing azotemia
  • Obstruction in a solitary kidney
  • Intractable pain despite maximal conservative measures
  • Urosepsis
  • Renal colic–induced premature labor unresponsive to tocolytics
• Traditional treatment has consisted of initial placement of a percutaneous nephrostomy tube or insertion of a ureteral stent for temporary drainage.⁸ Ureteral stents and/or nephrostomy tubes are then changed at periodic intervals until postpartum, thus allowing delay of definitive treatment until completion of pregnancy.
• Ureteroscopy is gaining favor as a first-line approach to urinary calculi that require intervention.^{15, 25, 22, 17} Improved instruments and increased experience have led to successful outcomes with few complications. Disbanding of supposed limitations (anatomical distortion late in pregnancy) and resolution of many associated concerns (anesthesia, radiation) has resulted in the advocacy of previous opponents.^{26, 14} These significant changes represent a paradigm shift in intervention for urolithiasis in pregnancy unresponsive to conservative treatment.
• Ureteral stent placement: Internal stents are usually placed with ultrasound guidance or limited fluoroscopy with local anesthesia. This minimizes risks of radiation and anesthesia on the fetus. Increasing oral hydration and decreasing calcium intake is recommended to prevent stent encrustation secondary to urinary stasis, hypercalciuria, or infection. Replacing stents every 3-4 weeks and antibiotic prophylaxis are suggested to avoid urinary tract infection and calcification.⁸ Insertion of percutaneous nephrostomy tubes or ureteral stents is considered a minor procedure, yet repeated insertions or changes may have risks comparable with definitive ureteroscopy in a single setting.¹⁷ The obstetricians should be involved for fetal monitoring.
• • Ureteral stents often cause irritative voiding symptoms and chronic discomfort.²⁷ The physiologic hydroureteronephrosis of pregnancy has been found to aggravate that by allowing more frequent stent migration within the dilated system.²⁸ Parulkar and coworkers (1998) presented a group of 70 pregnant patients with urolithiasis; 19 patients required intervention, 15 of whom had ureteral stents placed. They reported that 5 of 15 patients (>30%) required subsequent manipulation because of migration, encrustation, or severe irritative symptoms.⁶
  • Denstedt and Razvi (1992) recommend limiting ureteral stent placement until after 22 weeks of pregnancy, with use of a percutaneous nephrostomy prior to that point.⁸ If a ureteral stent is indicated but cannot be placed with ultrasound guidance or if urosepsis is present, a percutaneous nephrostomy tube should be placed instead.
  • Disadvantages to internal ureteral stent include the following:
  • • Urinary tract infections and promotion of ascending infections
    • Hematuria
    • Irritative voiding symptoms and renal colic due to stent
    • Stent migration due to hydroureteronephrosis of pregnancy
    • Multiple procedures to change stent to avoid encrustation
    • Need for patient compliance and vigilant follow-up for stent change
• Percutaneous nephrostomy: Use this treatment modality in patients with urosepsis or pyonephrosis. This procedure can be performed with local anesthesia and ultrasound guidance. Nephrostomy tube placement allows for rapid and adequate decompression of the upper urinary tract, control of pain from the acute obstruction, and resolution of the infected hydronephrosis. Another advantage of placing a percutaneous nephrostomy tube is that it may be used for antegrade irrigation with an antibiotic solution to decrease the incidence of infection and tube encrustation.²⁹ Internalization of a double-J stent can be performed after recovery from the original illness. This procedure needs to be performed by a physician experienced in percutaneous procedures. Disadvantages to percutaneous nephrostomy include the following:
• • Bacteruria despite preventive antibiotics
  • Frequent obstruction, requiring change and or flushing
  • Cumbersome external appliance
  • Risk of bleeding
  • Discomfort
• Ureteroscopy and stone manipulation: Ureteroscopy allows for complete visualization of the entire ureter and renal pelvis, enabling accurate diagnosis and definitive treatment for urolithiasis. Anatomic distortion near the completion of pregnancy has long been thought to make ureteroscopy impossible; however, ureteroscopy has been found to be safe and effective in all stages of pregnancy.^{15, 25, 22, 17} They also found that rigid ureteroscopy could be performed on the entire urinary tract, even in advanced pregnancy.²² The above group of series, along with the work of Lemos and associates¹⁶, represent 68 patients who underwent ureteroscopy for diagnosis and/or treatment; no obstetrical complications were reported, and only one ureteral perforation was reported. The one perforation¹⁷ was treated successfully with a stent, and the child was born healthy at term.
• • Most ureteroscopies are performed in absence of radiation. In the above studies, radiation was used sparingly in only a few patients; furthermore, Ulvik et al (1995)¹⁷ and Scarpa et al (1996)²² used no radiation. Physiologic hydroureteronephrosis of pregnancy allows entry of the ureteroscope under direct vision without dilation of the ureteral orifice; dilation is rarely performed.^{4, 22, 17}
  • General anesthesia is rarely used. The vast majority of procedures have been performed with epidural or spinal analgesia with an element of sedation. Scarpa and coworkers (1996) performed ureteroscopies in 5 patients without anesthesia and used only neuroleptic anesthesia (fentanyl or propafol and atropine) on 10.²² Ulvik et al (1995) reports the used of sedation analgesia and feel that it may be preferred to spinal or general anesthesia.¹⁷ Both rigid and flexible scopes have been used successfully.
  • Kavoussi and associates (1998) suggest that definitive ureteroscopy may be preferable to stenting in select patients (particularly patients > 6 weeks prior to term).²⁸ Ulvik and associates (1995)¹⁷ found a significant decrease in hospital stay among ureteroscopy patients (mean, 2.7 d) compared with ureteral stent patients (mean, 7 d) of Stothers and Lee (1992)⁷.
  • Stone retrieval via ureteroscopy has been performed successfully in many forms.^{30, 15, 22, 17} These include holmium YAG Laser, pulsed dye laser, ballistic lithotriptor, ultrasonic lithotriptor, basket retrieval, and forceps crush and retrieval; all were used successfully without known complications. The holmium YAG laser, with less than 1 mm of penetration, has been used most frequently in the more recent studies.^{30, 15, 25} Ulvik and coworkers (1995) recommended against the use of the ultrasonic lithotriptor until further data can prove its safety in fear that the high-pitched noise may result in hearing injury to the fetus.¹⁷
  • Akpinar and associates (2006) presented the most recent experience of ureteroscopy in 7 patients.³⁰ The holmium laser was used with success in 6 patients and no stone was found in the seventh. They compared postoperative pain with or without a ureteral stent. They recommend routine stent placement with a string for 72 hours postoperation in order to reduce pain and analgesic requirements.
  • Contraindications to ureteroscopy include the following:⁴
  • • Stones larger than 1 cm
    • Multiple calculi
    • Sepsis
    • Transplanted kidney
    • Ureteroscopic inexperience or inadequate instruments
    • Absence of general OB services or high-risk OB services
• Open surgery: In the past, pregnant patients who required intervention for urolithiasis underwent open lithotomy or blind stone manipulation under general anesthesia, similar to the general population. However, more modern procedures used to surgically treat urolithiasis are performed without anesthesia or radiation and carry lower morbidity rates while maintaining equal or greater success rates. Consequently, open surgery is now used as a last resort. Open surgery is used if a stone must be removed before delivery because of complications of conservative or invasive management of urolithiasis, or if contraindications to ureteroscopy are present.
• Percutaneous nephrolithotomy (PCNL), when indicated, is best postponed until postpartum because of the risks to the fetus of anesthesia and radiation.⁴
• Extracorporeal shock wave lithotripsy (ESWL) is frequently used in the nongravid population; however, it requires frequent use of ionizing radiation, and the potential adverse effects of energy dispersion on the fetus are unknown. At this time, ESWL is contraindicated during pregnancy.³¹
• Surgical risk: Physiologic organ system changes increase specific perioperative risk factors in the pregnant patient. Special attention to these risk factors can help prevent associated morbidity to the mother and fetus.
• • Venous thromboembolism (VTE) and pulmonary embolism (PE): Pregnancy-related changes in the cardiovascular and hematologic systems create a hypercoagulable state and place the patient at increased risk of VTE and PE. The risk of venous thromboembolism is progressive throughout gestation and, in the third trimester, is estimated to be 5-6 times greater than that of a nongravid female.¹⁴
  • The increasing size of the gravid uterus changes the hemodynamics in the lower extremities. Compression of the great vessels by the uterus reduces the velocity of venous blood return, increases pressure, and increases the risk of stasis in the lower extremities.¹⁴ Hematologic changes include increased plasma levels of clotting factors VII, VIII, and X and fibrinogen²⁴, as well as a decrease in fibrinolytic activity¹⁴.
  • Low-dose heparin is considered safe and effective by some researchers and is recommended in patients with a history of thromboembolism.³²
  • Aspiration: Pregnancy-related changes in gastrointestinal function and relative anatomy increase the risk of inadvertent perioperative aspiration. These changes include compromised integrity of the gastroesophageal sphincter, decreased gastrointestinal motility, and a decrease in the pH of gastric secretions.²⁴ Intravenous proton pump inhibitors provide acid suppression and may be used in the perioperative period as prophylaxis for acid aspiration syndrome during induction of anesthesia.³³
• Fetal risks of anesthesia: Inhalation anesthetics readily cross the placenta because of their lipid solubility. These agents have been shown to increase risk of teratogenicity. General anesthesia should be avoided during the first trimester, after which the risk is minimal.⁴

Consultations

Management of pregnant patients with urolithiasis should always involve the patients' obstetrician. When treatment beyond conservative measures is indicated, for the fetus' safety, coordinated care with a neonatologist, an anesthesiologist, and even a radiologist is appropriate.

Diet

Dietary modification is the cornerstone of preventing urolithiasis. General recommendations include dietary moderation of high-oxalate foods and purines with an increase in fluid intake. Salt and sodium intake should also be moderated because of their tendency to increase fluid retention and hypercalciuria. Low-calcium diets frequently cause a paradoxical rise in calcium stone formation and are discouraged.

• Specific long-term dietary changes should ideally be based on objective information from the stone composition analysis and 24-hour urine chemistry determinations.
• A low-oxalate diet tends to prevent calcium oxalate stone formation. Common foods that are high in oxalate include chocolate, nuts, green leafy vegetables, coffee, spinach, beets, and tea. Moderation and proportionate reductions are suggested rather than complete avoidance of high-oxalate foods that the patient enjoys.
• While excessively high calcium ingestion is discouraged, unusually low-calcium diets can also increase stone production by allowing increased oxalate absorption from the gastrointestinal tract. Low calcium intake may also lead to a decrease in calcium bone deposition with associated osteopenia and osteoporosis. In general, one calcium meal per day is suggested. If a calcium supplement is being used by the patient, calcium citrate seems to be the least likely to increase calcium stone production because of a compensatory increase in urinary citrate excretion with this particular supplement.
• Drinking at least 2 qt of water per day decreases the risk of stone formation. Actually, recommending a fluid intake sufficient to generate a 24-hour urine volume of 2000 mL per day may be better. A patient guide to maintaining an increased urinary volume developed by Stephen W. Leslie, MD, FACS, may be helpful. This recommendation includes stones of all types. For those patients unable to drink the required amount of water, lemonade is a reasonable substitute. Lemon juice is high in citrate, which is a natural kidney stone formation inhibitor.
• A low-methionine diet has been reported to decrease the incidence of cystine stone formation. Methionine is a dietary precursor of cystine. However, this diet is unpalatable, and patient compliance is poor.
• Diets that are high in purines and green vegetables may increase the likelihood of stone formation. A low-purine diet decreases the risk of both uric acid and calcium stone formation. This diet requires avoidance of red meats, beef, chicken, fish and peanuts.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Nonsteroidal anti-inflammatory drugs used during the first 20 weeks of pregnancy are not recommended. They have been shown to be associated with an 80% increased risk of miscarriage over non-use in a study of 1055 women.³⁴ NSAID use is also linked to renal congenital abnormalities and fetal pulmonary hypertension³⁵ and may cause premature closure of the ductus arteriosus³⁶.

Drug Category: Narcotic analgesics

These agents are used to treat pain and provide patient comfort.

Drug Category: Analgesics

These agents are used to treat pain and to provide patient comfort.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Complications

• Pregnancy outcome is not appreciably worsened because of symptomatic urolithiasis. Occurring in about 10-20% of patients, urinary tract infection is the most common nonobstetric complication of urolithiasis in pregnancy. Premature labor associated with renal colic is rare but can occur. In the past, spontaneous abortion has been associated with a history of urolithiasis but is extremely rare today.
• Complications secondary to surgical interventions are more common in the pregnant population; however, they are becoming increasingly infrequent with increased experience and improved technology.
• Physiologic changes of pregnancy are associated with an increase in perioperative risk. Complications of any surgical procedure may include the following:
• • Aspiration
  • Deep vein thrombosis
  • Pulmonary embolism
  • Premature delivery
• Complications of internal stent placement may include the following:
• • Stent incrustation, which may be accelerated in pregnancy and require change every 3-4 weeks⁸
  • Infection
  • Sepsis
  • Stent migration
• Complications of percutaneous nephrostomy may include the following:
• • Recurrent obstruction necessitating frequent flushing or replacement
  • Infection or sepsis secondary to tube obstruction
  • Fetal harm secondary to prolonged anesthesia requirements and ionizing radiation
  • Premature delivery³⁷
  • Risk of bleeding caused by nephrostomy tube placement, tube dislodgement, and erosion
• According to recent studies, complications of ureteroscopy and intracorporeal lithotripsy in pregnancy are rare in experienced hands.^{16, 15, 25} The risk of complications may be mildly increased because of the anatomic changes of pregnancy; however, the possible complications do not differ from those in the general population. These types of risks include the following:
• • Ureteral injury
  • Perforation
  • Subsequent stricture formation
• Complications of open surgery include increased incidence of premature delivery. The rate of premature delivery after surgery is 6.5% during the first trimester, 8.6% during the second trimester, and 11.9% during the third trimester. Intrauterine growth restriction or premature birth (complication of receiving general anesthesia during pregnancy) is more likely.

Prognosis

• Diagnosis and treatment of urolithiasis in pregnancy is complex. However, advances in technology and experience allow urologists to provide accurate evaluation and succeed with either temporizing or definitive treatments. These can be accomplished safely, with little risk to the mother or fetus. With prompt evaluation and expeditious treatment, the prognosis is excellent.

Patient Education

• An excellent patient education guide, The Kidney Stones Handbook is available directly from the publisher, Four Geez Press, at 1-800-2KIDNEYS. It is the only book on kidney stones specifically written for patients and their families by a urology kidney stone expert. A quarterly newsletter is also available and can be ordered from the same publisher.
• For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Pregnancy, Kidney Stones, Blood in the Urine, Urinary Tract Infections, and Intravenous Pyelogram.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Spontaneous abortion
• Premature labor
• Urosepsis

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Jong M. Choe, MD, FACS, to the development and writing of this article

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication