US Pharm. 2013;38(8):HS4-HS8.
ABSTRACT: Calculi in the
urinary tract vary in composition, size, and location. Most kidney
stones are composed of calcium oxalate or calcium phosphate, and they
may lead to urinary obstruction, flank pain, hematuria, and an increased
infection predisposition. Acute kidney stone management requires a
thorough patient history, definitive diagnosis, supportive care, and
possible surgical intervention. Long-term management focuses on
addressing the underlying etiologies and preventing complications of
treatment. Pharmacists should continue to identify drug-induced causes,
promote public health information, and counsel patients on methods to
avoid recurrent stone formation.
Urolithiasis, or stone formation in the urinary tract,
includes ureterolithiasis (ureteral calculi) and nephrolithiasis
(renal/kidney calculi).1,2 Stones form when substances in the urine become highly concentrated and/or insoluble.1
They vary in size and location; while small stones usually pass with
minimal pain sensation, larger stones may remain in the ureter or
bladder, obstruct urine outflow, and cause severe pain (secondary to
muscular dilation and spasms) and/or bleeding.1
Based on survey data from 2001 to 2008 in the United
States, the lifetime prevalence of at least one kidney stone is up to
12% in males and 7% in females.3 Data from 2002 to 2007
demonstrated that there were more than 300,000 emergency room visits per
year for upper urinary tract stones.3 The majority of these
cases were in Caucasian males between 45 and 54 years of age who lived
in the Southern region of the U.S.—a locale colloquially named the
“kidney stone belt.”3,4
There are four predominant types of renal calculi: calcium
(80%), uric acid (9%), struvite (<10%), and cystine (<1%) stones.4
These may be found in the kidney (staghorn [pelvic and ≥2 calyces] or
non-staghorn [calyceal or pelvic]), ureter (proximal, middle, or
distal), and urinary bladder.4 Kidney stones may develop due to an overgrowth on sites of Randall’s plaque (e.g., calcium oxalate), growth on plugs from dilated ducts of Bellini (e.g., apatite), or in free solution (e.g., cystinuria).4
Inadequate fluid intake and/or urine output promotes urine
concentration, and both have been identified as the most important
factors promoting kidney stone production.1,2 Calcium stones
may form secondary to idiopathic hypercalciuria, resorptive
hypercalciuria, hyperoxaluria, hypocitraturia, and/or hyperuricosuria.5 Hyperoxaluria can occur with a high dietary intake of oxalate-containing foods (e.g., spinach, rhubarb, nuts, wheat bran).1,5 High intake of purine, a breakdown product of animal protein (e.g., eggs, fish), may lead to hypocitraturia or hyperuricosuria.1,5
Calcium intake from food is not implicated in calcium stone formation;
it binds intestinal oxalate and decreases calcium oxalate stone
Urine pH <5.5 promotes uric acid stone formation regardless of seemingly normal 24-hour uric acid levels.5 An autosomal recessive genetic disorder leads to cystine stones, typically at a urine concentration ≥300 mg/L.5
Struvite (magnesium ammonium phosphate) stones could develop in
patients with urine pH >7 and chronic genitourinary tract infections
by urease-producing bacteria (e.g., Proteus, Pseudomonas, and Klebsiella species).5 Calcium phosphate stones may also form as a result of urine alkalinization (pH >6.5) for calcium (i.e., hypocitraturia), uric acid, and cystine stones.4,5
In addition, several drugs could crystallize in the kidney to form
stones, due to supersaturation and/or insolubility at a certain urine pH
Staghorn, or small nonobstructing, stones may only produce mild-to-moderate symptoms (e.g., malaise).15
Otherwise, patients with acute kidney stones most likely seek medical
attention after experiencing severe flank pain (radiating inferiorly and
anteriorly), nausea and vomiting, and/or hematuria.15,16
Confirmatory tests are typically performed to
differentiate nephrolithiasis from infections, malignancies, and/or
musculoskeletal inflammation or spasms.17 Following a thorough patient history and physical examination, diagnostic imaging is required for confirming renal calculi.1,16 In pregnant patients, an ultrasound examination is indicated to avert radiation exposure.1,16 If patients previously had radiopaque calculi, a plain-film radiography could be used.16 Otherwise, noncontrast computerized tomography (NCCT) is most preferred because of its high sensitivity and specificity.1 NCCT also avoids the risk of contrast-induced kidney damage, particularly with serum creatinine levels >2 mg/dL.15 In all other patients, if NCCT is unavailable, intravenous urography (IVU) could be used to detect stones.1,15,16
A biochemical workup should be performed in addition to imaging.1,15
Basic analyses include a urinary sediment or dipstick test out of a
spot urine sample (for red and white blood cells, nitrite, and urine
pH); urine culture or microscopy; serum blood sample (for creatinine,
uric acid, ionized calcium, parathyroid hormone, sodium, potassium, and
phosphorous); CBC count with differential (for C-reactive protein); and
coagulation test (for international normalized ratio [INR] and partial
thromboplastin time [PTT]).1,15 After collecting and
straining urine, stone analysis should be performed in first-time
calculi formers using validated procedures (e.g., x-ray diffraction or infrared spectroscopy) and be repeated in most recurrent stone formers.1,15
Acute kidney stone management involves a combination of supportive care and pharmacotherapy.1,15 If patients present to the emergency department with signs and symptoms consistent with infection (e.g., fever,
chills, pyuria), empiric antibiotics should cover gram-positive and
-negative organisms, while considering local antibiogram data.17
Specialty consultations are indicated for patients at age extremes or
with debilitation, stones >5 mm in diameter, multiple stones,
hydronephrosis, pregnancy, refractory pain or nausea, or clinical
emergencies (e.g., urosepsis, anuria, renal failure).16,17
Regardless of the stone type diagnosed, patients should receive oral or IV hydration with at least 2 L of fluid.15,17
Normal saline (NS; sodium chloride 0.9%) could promote calcium-based
stone formation; therefore, dextrose 5% in water (D5W) with ½ NS may be
In patients with small stones and mild pain, acetaminophen is appropriate.15
For effective alleviation of moderate-to-severe pain, nonsteroidal
anti-inflammatory drugs (NSAIDs) or opioid medications should be
provided immediately (TABLE 2).1 Each drug class has
advantages and disadvantages, and pain management should consider the
patient’s renal function, ability to tolerate side effects, and dosing
Most calculi <10 mm in diameter exit the kidney and travel through the ureter.1,15,16
While spontaneous passage in urine depends on location and size,
ureteral stones <5 mm should pass within 6 weeks of diagnosis.1,16 Stones between 5 and 7 mm have about a 50% chance of being passed, while stones >7 mm might require urologic interventions.15
In select patients, 2- to 4-week trials of conservative management
(i.e., watchful waiting/observation) may be attempted, and medical
expulsive therapy (MET) could be utilized in individuals comfortable
with hastening ureteral stone (<10 mm) passage by several days (TABLE 3).1,15-28 These patients must also have well-controlled pain, preserved renal function, and no systemic infection.
MET includes alpha1-blockers and
dihydropyridine calcium channel blockers (e.g., nifedipine), which
possess antispasmodic activity and relax ureteral smooth muscles.1,15,17 Corticosteroids may be used in addition to these drugs, but they are not effective as monotherapy.1,15,17
Phosphodiesterase type 5 (PDE5) inhibitors (e.g., vardenafil,
sildenafil, tadalafil) demonstrate in vitro activity on ureteral smooth
muscles, but their utility as MET is unknown.20
Definitive therapy, which is based on stone type and etiology, is outlined in TABLES 4 and 5.1,5,15-18,28-30
Discharge Planning and Prevention
Prior to discharge, patients should receive information
about follow-up appointments in urologic clinics, potential surgical
procedures, definitive therapies, and methods for preventing or
minimizing kidney stone formation.15-17 They may need to
modify their diets to increase fluid intake, minimize oxalate-containing
food consumption, and/or limit animal protein intake.1,5 After
initial treatment for renal calculi, patients might continue taking a
combination of oral opioids and NSAIDs for pain control.16
Surgical procedures are indicated for the breakdown and
removal of stones that remain in the urinary tract, particularly in
patients with obstruction.1,15,16 These procedures include,
but are not limited to, extracorporeal shock wave lithotripsy (SWL),
ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL).1,2,15,16 Each depends on the size and location of the ureteral stone and is associated with various limitations and complications.1,2,15,16 Of note, patients should avoid medications that increase bleeding risk (e.g., NSAIDs, aspirin) several days prior to SWL.16
Following diagnostic imaging, the treatment of most acute
kidney stones is hydration and pain management. Although many factors
contribute to renal calculi formation, recurrence could be minimized.
Along with other health care professionals, pharmacists should be aware
of drug-induced causes and counsel patients to adhere to definitive
therapies and recommended diets.
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