Pregnancy and Urolithiasis
Urolithiasis is the most common cause of nonobstetrical abdominal pain that requires hospitalization among pregnant patients.The relative incidence and rate of recurrent calculi in pregnant patients (1 per 1500 pregnant patients) is similar to that in nonpregnant patients.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.
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 pathology.
Appendicitis, diverticulitis, or placental abruption was mistakenly diagnosed in 28% of patients in a 1992 study by Stothers and Lee.
Finally, most stones (64-84%) pass spontaneously with conservative treatment.However, if the calculus does not pass, it may initiate premature labor, produce intractable pain, cause urosepsis in the setting of 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 for urolithiasis in pregnant patients, while limited intravenous pyelography (IVP) or CT scanning is reserved for more complex cases.
Ideally, no ionizing radiation should be 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.
Prevention is the best cure for urolithiasis
PathophysiologyAlthough 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.
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.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.
Dilatation 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.
Swanson and associates (1995) observed that hydroureteronephrosis was not routinely found below the pelvic brim and was altogether absent in patients who had undergone urinary diversion
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 levels 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 significantly 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 is due to elevated levels of serum 1,25 dihydroxycholecalciferol .This hormone, which is secreted by the placenta, augments calcium absorption in the GI tract and suppresses parathormone production, increasing 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 with that in 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 form only 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 in the presence of a congenital abnormality of the collecting system.Mortality/Morbidity
Urolithiasis associated with ureteral obstruction and upper urinary 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.Clinical
HistoryUrolithiasis 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.
Alternatively, pregnant patients with ureteral stones may report pain in atypical locations or the pain of premature labor. Signs of premature labor, ectopic pregnancy, or complicated labor often 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.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.
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.
palpation, the abdomen is soft and tender in the upper quadrant. This differs significantly from the motionless presentation and rigid abdomen of a patient with peritonitis.
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.
Laboratory Studies
Urinalysis - To assess for microscopic hematuriaThe presence of red blood cells may suggest a calculus.Using both dipstick and microscopic analysis can identify microscopic hematuria in 95% of patients with urinary stones.
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%.
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 infectionRenal panel (serum chemistries)
Decreased serum bicarbonate and potassium levels suggest an underlying renal tubular acidosis that may result in the formation of calcium phosphate stones. Elevated serum calcium levels 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.
Metabolic stone prevention studies
(ie, 24-hour urine collection)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.
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.
The use of ionizing radiation during pregnancy is a complicated and controversial issue. Radiographic studies should be used judiciously and avoided when possible, particularly during the first trimester.
The guidelines available from the American College of Obstetricians and Gynecologists (ACOG) state, “concern about possible effects of high-dose ionizing radiation exposure should not prevent medically indicated diagnostic x-ray procedures from being performed on a pregnant woman.
During pregnancy, imaging procedures not associated with ionizing radiation (eg, ultrasonography, MRI) should be considered instead of x-rays when appropriate.” Concerning fetal dosages of radiation, ACOG states that “....less than 5 rads (5000 millirad [mrd]) has not been associated with an increase in fetal abnormalities or pregnancy loss.
Srirangam et al (2008) reported average fetal radiation doses for common diagnostic procedures used in the workup of urolithiasis in pregnancy, as follows:Ultrasonography - None
MRI (<1.5 T) - None
KUB, 1.4 milligray (mGy) - 140 mrd
Intravenous urography, 1.7 mGy - 170 mrd
Renal tract CT scanning, 80 mGy - 800 mrd
Technetium Tc 99m renal scan (mercaptoacetyltriglycine [MAG-3] or diethylenetriaminepentaacetic acid [DTPA]), 0.2 mGy - 20 mrd
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.
Radiation exposure in the third trimester is less of a risk to the fetus.
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%, yet Parulkar et al (1998) reported 95% and 87%, 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: 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.Loughlin and Ker (2002) endorse the use of a transrectal ultrasonography probe if a vaginal transducer is unavailable.
ultrasonography with Doppler studies enables recording of waveform tracings of the renal vasculature. Ureteric obstruction increases 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.
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
• 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
• 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 pregnancyRI value of less than 0.70 in both kidneys
Symmetric ureteral jets
No specific calculus identified
The following results indicate a high probability of urolithiasis during pregnancy:
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 0.60
Dilated ureter extending below the level of the iliac arteries
Asymmetry of ureteral jets
Identification of calculus
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 0.004-0.01 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.
Indications for excretory urography in a pregnant patient may include the following:
Sonography results that are equivocal for pregnancy dilatation or urolithiasisAzotemia 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 intravenous 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 high-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.MRI does provide a benefit in its ability to reveal non–urinary-tract pathology that may manifest with similar symptoms (ie, ovarian torsion, appendicitis).
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
using technetium Tc 99m 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 anexcellent 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.
A drainage half-time of 20 minutes or more indicates obstruction, whereas a drainage half-time of 10 minutes or less indicates nonobstruction.
Washout or drainage half-times of 10-20 minutes are considered indeterminate.
Unenhanced helical CT scanning: This reported to be highly sensitive (96-97%) and specific (96-99%) and has become the criterion standard in the diagnosis of urinary calculi. It is also effective in differentiating calculi from tumors or blood clots.
Despite these benefits, this study has traditionally been avoided in pregnant patients.
Recently, White et al (2007) reported on the use of low-dose CT scanning in pregnant patients with suspected urinary calculi, with an average radiation dose of only 705.5 mrd. They assert that this offers an acceptable degree of risk, and they advocate its use in the setting of refractory flank pain and inconclusive ultrasonographic results in pregnant patients.
However, the use of CT scanning or any study that involves radiation should be avoided when possible, and patients should be counseled appropriately.
Procedures
UreteroscopyUreteroscopy has emerged as a safe and efficient way to treat urolithiasis during pregnancy. Ulvik and associates (1995) have used ureteroscopy to successfully treat urolithiasis and consider it as a diagnostic procedure in difficult cases.Rigid or flexible ureteroscopes may be used, but Ulvik et al feel that flexible scopes may be better suited in diagnosis during pregnancy. 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
Medical CareThe initial management of urolithiasis in pregnancy should be conservative. Intravenous hydration and analgesia have been shown to result in spontaneous passage of symptomatic calculi in 64-84% of patientsBed 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.
Treatment goals in 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.
(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.
Medical expulsive therapy (MET): Ureteral stone passage may be facilitated by alpha-adrenoceptor blockers. These agents promote relaxation of ureteral smooth muscle and have been found to increase rates of stone passage, to hasten stone passage, and to decrease the amount of pain associated with stone passage.
Although these studies have not addressed the use of alpha-adrenoceptor blockers in pregnant women, the authors have successfully used alpha-blockade as MET therapy in several pregnant patients with ureterolithiasis in conjunction with the attending obstetrician. The authors recommend that consultation with the attending obstetrician is recommended before this therapy is instituted.
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 increasing 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 penicillamine has been reported to cause fetal abnormalities in rats, it is contraindicated during pregnancy.
Increasing urinary volume to 3000 mL 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/24 h) 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.
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 is required in 20-30% of pregnancies complicated by urolithiasis. Surgical treatments are somewhat limited and are used to provide 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 pregnancy; 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 obstetrician 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. Ureteral stents and/or nephrostomy tubes are then changed at periodic intervals until delivery, 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. 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 advocacy from previous opponents.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 to 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.
Insertion of percutaneous nephrostomy tubes or ureteral stents is considered a minor procedure, yet repeated insertions or changes may carry risks comparable with those of definitive ureteroscopy in a single setting.The obstetrician should be involved for fetal monitoring.
Ureteral stents often cause irritative voiding symptoms and chronic discomfort.The physiologic hydroureteronephrosis of pregnancy has been found to aggravate that by allowing more frequent stent migration within the dilated ,report s >30% required subsequent manipulation because of migration, encrustation, or severe irritative symptoms.
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.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
• Stent migration due to hydroureteronephrosis of pregnancy
• Multiple procedures to change stent to avoid encrustation
• Need for patient compliance and vigilant .
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 due to 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 risk of infection and tube encrustation. 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 antibioticsFrequent obstruction, requiring change and/or flushing
Cumbersome external appliance
Risk of bleeding
Discomfort
Ureteroscopy and stone manipulation: 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.
Physiologic hydroureteronephrosis of pregnancy allows entry of the ureteroscope under direct vision without dilation of the ureteral orifice; dilation is rarely performed.
General anesthesia is rarely used. The vast majority of procedures have been performed with epidural or spinal analgesia with an element of sedation.
Stone retrieval via ureteroscopy has been performed successfully in many forms. 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.
Contraindications to ureteroscopy include the following:
• Stones larger than 1 cm• Multiple calculi
• Sepsis
• Transplanted kidney
• Ureteroscopic inexperience or inadequate instruments
• Absence of general obstetrical services or high-risk obstetrical 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.
Extracorporeal shockwave 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.
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.
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.Hematologic changes include increased plasma levels of clotting factors VII, VIII, and X and fibrinogen, as well as a decrease in fibrinolytic activity .
Low-dose heparin is considered safe and effective by some researchers and is recommended in patients with a history of thromboembolism.
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.
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.
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.Consultations
Management of pregnant patients with urolithiasis should always involve the 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 qt1 quart (qt) = 2 pints. 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. In patients unable to drink the required amount of water, lemonade is a reasonable substitute. Lemon juice is high in citrate, which is a natural inhibitor of kidney stone formation.
A low-methionine diet has been reported to decrease the risk 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
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Nonsteroidal anti-inflammatory drugs are not recommended during the first 20 weeks of pregnancy. increased risk of miscarriage.NSAID use is also linked to renal congenital abnormalities and fetal pulmonary hypertension and may cause premature closure of the ductus arteriosus.
Narcotic analgesics
These agents are used to treat pain and provide patient comfort.
Butorphanol (Stadol)
Mixed agonist-antagonist narcotic with central analgesic effects for moderate to severe pain. Causes less smooth muscle spasm and respiratory depression than morphine or meperidine. Weigh advantages against increased cost of butorphanol.Dosing
Adult0.5-2.9 mg IV q3-4h prn; 1-4 mg IM q3-4h prn
Pediatric
Not established
Interactions
Toxicity increases with guanabenz, MAOIs, CNS depressants, phenothiazines, barbiturates, and skeletal muscle relaxants
Contraindications
Documented hypersensitivityPregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in hepatic or renal insufficiency; respiratory limitations (eg, bronchial asthma, obstructive respiratory conditions, cyanosis); may increase CSF pressure and cardiac overload; causes respiratory depression
Meperidine (Demerol)
Analgesic with multiple actions similar to those of morphine but may produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine.
Dosing
Adult
50-150 mg PO/IV/IM/SC q3-4h prn50 mg PO q4h or 25 mg IM q4h in elderly patients
Pediatric
Not establishedInteractions
Monitor for increased respiratory and CNS depression with co-administration of cimetidine; hydantoins may decrease effects of meperidine; avoid with protease inhibitors; may aggravate adverse effects of isoniazid; MAOIs, fluoxetine, and other SSRIs greatly potentiate the effects of meperidine; CNS depressants, tricyclic antidepressants, and phenothiazines may potentiate effects.
Contraindications
Documented hypersensitivity; MAOIs; upper airway obstruction or significant respiratory depression; during labor when delivery of premature infant is anticipatedPrecautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals.
Precautions
Caution in patients with head injuries because meperidine may increase respiratory depression and CSF pressure (use only if absolutely necessary); caution when using postoperatively and with history of pulmonary disease (suppresses cough reflex); substantially increased dose levels because of tolerance may aggravate or cause seizures even if no prior history of convulsive disorders exists.Morphine sulfate (Oramorph, MS Contin, Duramorph)
Criterion standard for relief of acute severe pain; may be administered in various ways; commonly titrated until desired effect obtained. IV morphine demonstrates half-life of 2-3 h; however, half-life may be 50% longer in elderly patients.Dosing
Adult
Loading dose: 0.1 mg/kg IV/IM/SCMaintenance dose: 5-20 mg/70 kg IV/IM/SC q4hRelatively hypovolemic patients: Start with 2 mg IV/IM/SC and reassess hemodynamic effects of dose
Pediatric
0.11-0.2 mg/kg/dose IV; then titrate carefully to adequate pain relief
Interactions
Phenothiazines may antagonize analgesic effects; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effectsContraindications
Documented hypersensitivity; hypotension; potentially compromised airway in which establishing rapid airway control would be difficult
Precautions
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid in hypotension, respiratory depression, nausea, emesis, constipation, and urinary retention; caution in atrial flutter and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate
Hydromorphone (Dilaudid)
A hydrogenated ketone of morphine. Hydromorphone is a narcotic analgesic. Analgesic action of parenterally administered Dilaudid is apparent within 15 min and usually remains in effect for >5 h.Adult
1-2 mg IV q2-4h
Pediatric
Not recommended
Interactions
Hydantoins may decrease effects; phenothiazines, CNS depressants, and tricyclic antidepressants may increase toxicity
Contraindications
Documented hypersensitivity; obstetrical analgesia; increased intracranial pressure; respiratory depression; ulcerative colitis; Crohn disease; abdominal cramping and distentionPrecautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with head injuries because may increase respiratory depression and CSF pressure (use only if absolutely necessary); caution postoperatively and with history of pulmonary disease (suppresses cough reflex); increased dosing levels, because of tolerance, may aggravate or cause seizures (even without prior history); adjust dose in renal insufficiency (do not use in severe renal dysfunction).Normeperidine metabolite accumulation may induce CNS toxicity; monitor closely for morphine-induced seizure activity if prior seizure history
Analgesics
These agents are used to treat pain and to provide patient comfort.Acetaminophen (Tylenol)
Inhibits prostaglandin synthesis in the CNS and peripherally blocks pain impulse generation. Produces antipyresis from inhibition of hypothalamic heat-regulating center.
Dosing
Adult325-650 mg PO q4-6h; 1000 mg tid/qid; not to exceed 4 g/d
Pediatric
Not established
Interactions
Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Contraindications
Documented hypersensitivity; known G-6-P deficiency
Precautions
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Overdose may cause severe hepatic toxicity; use with caution in patients with alcoholic liver disease.
Alpha-adrenergic blocking agent, oral
These agents relax smooth muscle to facilitate ureteral stone passage.Tamsulosin (Flomax)This alpha-1 selective blocker is indicated for the treatment of lower urinary tract symptoms due to prostatic enlargement. An off-label use, as discussed above, is to facilitate passage of ureteral stones. Only short-term therapy (10 d) should be considered for this indication.
Dosing
Adult0.4 mg tab PO qd
Pediatric
Not established
Interactions
Cimetidine may significantly increase plasma concentrations; tamsulosin may increase toxicity of warfarin
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Not for use as antihypertensive drug; may cause orthostasis; avoid situations that may result in injuries if syncope occurs; rule out presence of carcinoma or cancer before initiating treatment
Follow-up
Deterrence/Prevention
See Diet.
Complications
Symptomatic urolithiasis does not appreciably worsen pregnancy outcome. 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 weeksInfection
Sepsis
Stent migration
Complications of percutaneous nephrostomy may include the following:
Recurrent obstruction necessitating frequent flushing or replacementInfection or sepsis secondary to tube obstruction
Fetal harm secondary to prolonged anesthesia requirements and ionizing radiation
Premature delivery
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.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 an increased risk 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.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.
