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UROGYN UPDATE
Kidney Stones and Pregnancy
Matthew E. Karlovsky, MD
Common Clinical Scenario: KJ is a 26-year-old primigravid woman, 28 weeks’ pregnant, who woke up with severe right flank pain, chills, and a fever of 100.1°F. Ultrasound examination in the emergency department revealed severe right-sided hydronephrosis, but no stone was seen. However, KJ’s mother and brother both have a history of kidney stones. She was begun on IV hydration and given acetaminophen and morphine, and urine and blood cultures were drawn. Urine dip showed red and white cells as expected. Intravenous cefazolin was also ordered prophylactically.
Urolithiasis is characterized by urinary calculi, or stones, anywhere along the urinary tract. Stones are abnormal concretions of crystals often mixed with a protein matrix. Urolithiasis affects approximately 1% to 5% of the population in industrialized countries and complicates 1 in 200 to 2,000 pregnancies, with a women’s lifetime risk of stone formation at approximately 5% to 10%.1 The rate of stone formation during pregnancy mimics that found in the general female population.
Most stones are a composite of calcium salts, with the most common in pregnancy being calcium phosphate.2 Either kidney can form stones equally without predilection, but the most common site of stone presentation in the pregnant woman is the ureter. Minimally invasive techniques can help relieve an obstructed kidney and allow stones to pass during pregnancy. Prompt and proper management will help to readily diagnose the problem and potentially prevent preterm labor, one of the more serious consequences of stone formation.
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PATHOPHYSIOLOGY
Urinary tract changes during pregnancy are well described. Hydronephrosis can begin as early as the 6th week of gestation and continue until approximately 1 month postpartum. It occurs in up to 95% of pregnant women and is a result of both physiologic and mechanical changes.3 Compression of the ureters, right more than left, by the gravid uterus is the main cause, as well as compression by an engorged right ovarian vein.4 In addition, high progesterone levels lead to relaxation of ureteral smooth muscles, slowing peristalsis of urine from the kidneys and leading to dilation of the ureter.
High levels of progesterone, aldosterone, and human chorionic gonadotropin lead to changes in cardiac output that are responsible for increasing the glomerular filtration rate (GFR) and renal plasma flow (RPF) by approximately 25% during pregnancy. As a result, there is a large increase in excretion of urinary metabolites. Urinary levels of sodium and uric acid that potentiate stone formation become elevated. By contrast, citrate, magnesium, and glycosaminoglycans all inhibit stone formation. Urinary calcium excretion is raised 2 to 3 times as a result of increased production of 1,25-dihydroxycholecalciferol by the placenta.5 Elevated vitamin D levels, in turn, promote absorptive hypercalciuria. Interestingly, the elevated calcium levels are countered by raised excretion of stone inhibitors and increased urine output as a result of elevated GFR and RPF. This would explain the finding that pregnant women have no higher risk for stone formation than their nonpregnant counterparts.
Most kidney stones are an amalgamation of calcium salts, with calcium binding to either oxalate or phosphate. Serum supersaturation of oxalates and uric acid helps to create the ideal environment for stone crystallization. Uric acid itself can crystallize into stones, but it can also act as a nidus for calcium stone formation. Struvite, or infection, stones are composed of magnesium ammonium phosphate and are overall uncommon, but they are found 3 times more often in women than men. Urea-splitting bacteria (Proteus, Providencia, Serratia, and Klebsiella, but not Escherichia coli) that commonly cause urinary tract infections release ammonium from urea, which in turn raises urine pH above 7.5, resulting in struvite crystallization.
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DIAGNOSIS
Acute onset of abdominal pain in the pregnant patient prompts a wide differential diagnosis that includes appendicitis, diverticulitis, and urolithiasis. In addition to nonobstetric diagnoses, women with pain may also be in labor or have other complications such as placental abruption. Misdiagnosis is common, due to the wide number of diagnoses. Most acute pain resulting from obstructing stones will manifest in the second and third trimesters in up to 90% of patients, but the presenting signs and symptoms may still be nonspecific. In a large cohort study, hematuria, either microscopic or gross, was seen in 95% of pregnant women presenting with stones, with flank pain seen in 89%.5
Conventional radiography for stone diagnosis, such as noncontrast spiral computed tomography (CT) or intravenous pyelography (IVP), is routinely avoided due to fetal risk associated with x-ray exposure. Ultrasound of the kidneys is the most widely accepted imaging modality for pregnant women, due to its lack of radiation and reasonable ability to detect kidney stones. In general, ultrasound is suboptimal for detecting stones smaller than 4 mm and thus has a sensitivity and specificity for stone diagnosis of 34% and 86%, respectively, underlining its limits.6 Ultrasound can detect the presence of hydronephrosis, but this may not always suggest the presence of an obstructing stone. Commonly, benign gestational hydronephrosis will cause flank pain and mimic stone presentation. Ultrasound typically cannot be used to image normal caliber ureters, but with obstruction, hydroureter can be detected. Bladder ultrasound is often performed to visualize ureteral jets of urine, but the presence of a ureteral jet does not rule out the presence of a partially obstructing ureteral stone.
Magnetic resonance imaging (MRI) is a potentially safe alternative to CT or IVP for renal imaging in the pregnant patient; however, MRI diagnosis of urolithiasis is suboptimal when compared with conventional x-ray. Limited use can be made of a single kidney, ureter, and bladder (KUB) x-ray or “limited IVP.” However, there is little information about IV contrast safety on the fetus, so these are generally discouraged, since ultrasound is widely available and a high degree of diagnostic suspicion, coupled with a urinalysis, often suffices in making the diagnosis.
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TREATMENT
When dealing with a suspected obstructing stone, it is always prudent to rule out concomitant urinary tract infection and treat accordingly. “Aggressive” conservative therapy, with analgesics, hydration, and antibiotics, is the mainstay of treatment and can facilitate passage of the stone or resolution of symptoms in 70% to 80% of women.4 Common medications used to expedite stone passage in the general population, such as α-blockers, are not routinely used in pregnant patients, since first-trimester studies are not available.
For women in whom conservative management fails, intervention becomes necessary if pain cannot be controlled or risk for sepsis or solitary kidney is present. The goal is decompression of the obstructed or infected system and restoration of normal kidney function. This can be achieved with either a percutaneous nephrostomy tube or ureteral stent. In most institutions, nephrostomy tubes are placed by an interventional radiologist and can be performed under sedation with local analgesia, using ultrasound or limited fluoroscopy. Ureteral stents require either a spinal or general anesthetic. Advantages of a nephrostomy tube include direct renal access, no need for general anesthesia that may provoke preterm labor, and easy access to the tube when tube changes become necessary or if drainage becomes occluded. Ureteral stents are internal and do not require an external drainage bag, unlike nephrostomy tubes. They can be placed blindly or with a single KUB exposure, and placement can be confirmed with ultrasound of the kidney.
If the stone is suspected to be in the distal ureter, ureteroscopy can be safely performed, whether with rigid or flexible scopes. The ureter is relatively dilated due to progesterone, and laser can be used to break up stones, which can then be removed with baskets. A recent review of ureteroscopy in 108 pregnant patients showed no increased risk for complications when compared with nonpregnant individuals, indicating that ureteroscopy can be employed as a first-line treatment.7 Ureteroscopy use is limited only by the skill and comfort level of the urologist in operating on a pregnant patient. Many urologists prefer ureteral stenting over nephrostomy tubes for decompression, but practice patterns vary.
Common complications of both ureteroscopy with stenting and nephrostomy tube placement include bleeding, sepsis, tube/stent dislocation or occlusion, and ureteral perforation with stents. Compression of the ureter by a gravid uterus may make ureteroscopy difficult later in pregnancy, but if ureteral stents are to be used, they should be reserved for late pregnancy to avoid multiple anesthetic exposures to the fetus for stent changes.
Other common minimally invasive treatments for stones, such as extracorporeal shockwave lithotripsy and percutaneous nephrolithotomy, should be avoided in pregnancy because of potential prolonged operating times, fluoroscopic exposures, and unknown effects of shockwave energy on the gravid uterus and developing fetus.
Open surgery has been nearly replaced by the endourologic techniques noted above and is considered only if such minimally invasive techniques fail. The risk for preterm labor with open surgery and anesthesia increases in relation to the trimester in which the surgery is performed; one study reported the risk for preterm labor was 6.5%, 8.6%, and 11.9% for first, second, and third trimesters, respectively.3 When factoring together all potential risks in terms of acute stone presentation, intervention, and anesthesia, the risk for preterm labor can rise as high
as 40%.3
When counseling a nulliparous woman who may be planning pregnancy, a medical history of kidney stones or family history of stone disease should be elicited. If positive, urologic assessment with x-ray examination and metabolic work-up should be undertaken to establish whether stones are present, as well as whether any stones found should be treated prophylactically prior to potential pregnancy. Strong consideration should be given to treatment prior to planned pregnancy if large or multiple stones are evidenced. If a stone pre-sents during pregnancy, prompt urology consultation should be obtained to evaluate and determine need for intervention.
Conclusion to clinical scenario presented above: KJ’s fever resolved after 24 hours of observation, and cultures were negative after 48 hours, so antibiotics were discontinued. Her pain was reasonably controlled with hydrocodone, thus ureteral stenting or ne-phrostomy tube placement was not ultimately necessary. The patient was counseled that renal colic may recur prior to delivery and, if severe, may neccessitate readmission. CT evaluation was planned for postpartum.
The author reports that he is a speaker for Allergan, Proctor & Gamble, and Novartis and a proctor for Boston Scientific.
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Matthew E Karlovsky, MD, is Director, Female Pelvic
Health, Center for Urological Services, Phoenix, AZ.
References
- Gorton E, Whitfield HN. Renal calculi in pregnancy. Br J Urol. 1997;80(Suppl 1):4-9.
- Ross AE, Handa S, Lingeman JE, Matlaga BR. Kidney stones during pregnancy: an investigation into stone composition. Urol Res. 2008;36(2):99-102.
- Biyani CS, Joyce AD. Urolithiasis in pregnancy, II: management. Br J Urol. 2002;89(8):819-823.
- Srirangam SJ, Hickerton B, Van Cleynenbreugel B. Management of urinary calculi in pregnancy: a review.
J Endourol. 2008;22(5):867-875.
- Swanson SK, Heilman RL, Eversman WG. Urinary tract stones in pregnancy. Surg Clin North Am. 1995;75(1):123-142.
- Drago JR, Rohner TJ, Chez RA. Management of urinary calculi in pregnancy. Urology. 1982;20(6):578-581.
- Semins MJ, Trock BJ, Matalga BR. The safety of ureteroscopy during pregnancy: a systematic review and meta-analysis. J Urol. 2009;181:139-143.
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