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Chapter 24 / Management of Ureteral Calculi 455
IV
TREATMENT
Chapter 24 / Management of Ureteral Calculi 457
457
From: Current Clinical Urology, Urinary Stone Disease:
A Practical Guide to Medical and Surgical Management
Edited by: M. L. Stoller and M. V. Meng © Humana Press Inc., Totowa, NJ
24
Conservative Management
of Ureteral Calculi
Christopher J. Kane, MD
CONTENTS
INTRODUCTION
OBSERVATION OF URETERAL CALCULI
MEDICAL MANAGEMENT TO ENHANCE PASSAGE
OF
URETERAL CALCULI
RENAL INJURY DURING PERIODS OF OBSERVATION
OBSERVATION IN CHILDREN
COST
INDICATIONS FOR INTERVENTION
CONCLUSIONS
REFERENCES
Key Words: Ureter; calculi; kidney; calcium channel blockers; steroids;
β-blockers; obstruction.
INTRODUCTION
Urolithiasis is a common condition affecting up to 12% of the US population (1). The
majority of patients initially present with pain or hematuria. Approximately 60–70%
of patients presenting to an emergency department with flank pain who undergo imag-
ing will be diagnosed with ureterolithiasis (2). Of those patients with ureterolithiasis,
depending on stone size and location, approx 80% will pass the stone spontaneously if
given an opportunity (3). The widespread use of shockwave lithotripsy and ureteroscopy
has prompted earlier intervention of ureteral calculi with excellent results. However,
observation is the most appropriate initial management in the majority of patients with
symptomatic urolithiasis because of its noninvasiveness, success, and low cost. This
chapter will examine the spontaneous passage of ureteral calculi, factors predictive of
458 Kane
successful conservative management, options available for medically enhancing stone
passage, as well as the effects of obstruction and indications for intervention of ureteral
calculi.
OBSERVATION OF URETERAL CALCULI
It has long been recognized that many ureteral calculi pass spontaneously. The
American Urological Association (AUA) clinical guidelines panel for the management
of ureteral calculi recommends observation for stones less than 5 mm in size (4). How-
ever, observation of ureteral calculi, although attractive because of its noninvasiveness,
is associated with significant uncertainty. The time interval of spontaneous passage is
important, as are the pain expectations, time off from work, and potential risk of renal
injury (Fig. 1). Specifically, in order to select appropriate therapy, it is important to know
which stones should be observed, how long a patient should expect to wait before stone
passage, and which factors are predictive of spontaneous passage.
The likelihood of stone passage by size varies widely in the literature from 71–98%
for stones under 5 mm in the distal ureter to 25–53% for stones 5–10 mm in the same
location (4). In a review of 75 patients with ureterolithiasis followed until spontaneous
stone passage or intervention, Miller and Kane found that stone passage was dependent
on a number of factors including stone size. Ninety-five percent of stones 2 mm and
smaller passed spontaneously, whereas 83% of stones 2–4 mm and only 50% of stones
over 4 mm passed spontaneously (3). Miller and Kane also analyzed the impact of
clinical factors including patient gender, age, stone size, location, pain medication
requirements, and interval to stone passage. Multivariate analysis revealed that patient
sex, age, and degree of pain were unrelated to interval to stone passage. Together, size,
location, and side were statistically related to stone passage interval (p = 0.012). Stones
that were smaller, more distal, and right sided were more likely to pass spontaneously
and required fewer interventions. The time interval to stone passage was quite variable,
however, and was highly related to location and size. The average interval to stone
passage by size is summarized in Figure 1 and is typically 1–2 wk for stones less than
5 mm. For 95% of stones of a particular size to pass spontaneously, however, much
longer intervals, up to 30–40 d, may be required. The likelihood of intervention in their
cohort also went up with stone size from only 5% for 2 mm stones to 50% for over 4 mm
stones.
Hubner et al evaluated a cohort of 100 patients managed with observation and found
that no stone larger than 6 mm passed spontaneously (5). They also found that compli-
cations increased significantly with time, with 20% complications after 4 wk compared
Fig. 1. Average days to stone passage for ureteral stones by size. Adapted from Reference 3.
Chapter 24 / Management of Ureteral Calculi 459
to only 7% complications under 4 wk. Ibrahim analyzed prognostic factors in the con-
servative management of ureteral stones. Factors predictive of spontaneous stone pas-
sage for stones 10 mm included: duration of pain <30 d; pyuria <100 white blood cells/
high powered field; lack of irregular stone surface and partial obstruction.
MEDICAL MANAGEMENT TO ENHANCE
PASSAGE OF URETERAL CALCULI
Pain and Nausea Treatment
The cornerstone of medical management of ureteral stones has been pain control. The
most common agents used are oral narcotics and nonsteroidal antiinflammatory medi-
cations. There is no evidence that oral narcotics either speed or diminish ureteral stone
passage; however, patient comfort is necessary in order to tolerate observation. Oxyco-
done is a potent, well-tolerated oral narcotic that retains 50% of its effectiveness when
taken orally and is used most commonly in combination with acetaminophen. Narcotics
act primarily centrally. Because acute ureteral obstruction and oral narcotics can both
lead to nausea, antiemetics are also beneficial to some patients. We most commonly use
prochlorperazine in oral or suppository form, which has been shown to be superior to
placebo in treating nausea and vomiting (7). Intravenous administration of intramuscular
ketorolac is an effective treatment for acute renal colic. It blocks the synthesis of pros-
taglandin E2 from the renal medulla, thus decreasing glomerular filtration rate and urine
output. It also acts centrally to decrease pain, acts locally to decrease ureteral spasm and
may diminish ureteral edema (8–10). Ketorolac is a commonly used agent for control of
acute colic but is used less commonly in the outpatient setting. A study of the prostag-
landin synthesis inhibitor diclofenac sodium in 80 patients with ureterothiasis under
5 mm confirmed excellent analgesia in 84% of patients and suggested enhanced stone
passage (57.5%) although there was no untreated control group (11).
Oral Steroids, Calcium Channel Blockers, and Beta Blockers
There has been growing evidence that the combination of oral steroids and long-
acting calcium channel blockers enhances passage of ureteral calculi (Table 1). Borchi
et al. performed a prospective randomized double blind study comparing 16-mg methyl-
prednisolone and 40 mg of nifedipine daily to the same dose of steroid and placebo on
86 patients followed until stone passage or 45 d (12). The treatment group had a higher
Table 1
Randomized Controlled Trials of Calcium Channel Blockers and Steroids for Stone Passage
Treatment arm Control arm
Passage Passage
Reference N Medication (%) Days (%) Days
Borchi (12) 86 Nifedipine + methylprednisolone 86 11.2 65 16.4
Porpiglia (13) 96 Nifedipine + deflazacort 79 7 35 20
Cooper (14) 70 Nifedipine 86 56
460 Kane
spontaneous passage rate (87 vs 65%, p = 0.021) and passed the stones more quickly
(mean 11.2 vs 16.4 d, p = 0.036). The stones which successfully passed in this series were
6.4 and 5.3 mm in the different treatment groups, which is fairly large for spontaneous
passage series.
In a similar prospective study, Porpiglia et al. studied 96 patients with distal ureteral
stone under 1 cm (13). The patients were randomized between (1) oral 30-mg deflaza-
cort and 30-mg slow-release nifedipine and (2) placebo. The passage rates were 79% in
the treatment arm and 35% in the placebo arm (p < 0.05) and the treatment arm passed
stones more quickly (mean 7 d vs 20 d, p < 0.05). Porpiglia et al. also examined the pain
medication used by each patient and found that the steroid and nifedipine arm had
significantly less pain medication usage, mean 15-mg sodium diclofenac vs 105 mg in
the placebo arm. Transient hypotension and palpitations led to discontinuation in two
patients of the treatment arm. Twenty-one percent of patients had side effects from
treatment including headache and asthenia that did not require discontinuation. The
treatment arm also experienced a mean decrease of systolic blood pressure of 15 mmHg.
Cooper et al. also performed a prospective randomized study comparing standard pain
management and nausea medication to a group receiving the same regimen plus nifedi-
pine, prednisone, and trimethoprim/sulfamethoxazole (14). They found the nifedipine/
steroid/antibiotic group had higher spontaneous stone passage (86% vs 56%) and fewer
lost work days (1.8 vs 4.9), emergency room visits, and surgical interventions. Because
of the study design, it was impossible to determine which agent was responsible for the
beneficial effects.
The mechanism by which calcium channel blockers enhance stone passage is not
completely understood. Ureteral contractions are dependent on an active calcium pump.
Calcium channel blockers appear to suppress the intensity of ureteral contractions (15)
and, in an animal model (16), decrease the number of ureteral contractions per minute.
For this reason, they are effective at relieving renal colic pain acutely (17). The improved
passage is likely caused by diminished ureteral spasm in the region of the calculus and
perhaps caused by direct ureteral relaxation. The mechanism of action of steroids is
likely because of their antiinflammatory effects and presumably from effecting local
inflammation and edema. A short course of oral steroids, as was used in the studies
summarized, does not require a steroid taper after discontinuation.
β-blockers have been less extensively studied. In a prospective controlled trial involv-
ing 86 patients with distal ureteral stones, Bajor found that oxprenolol reduced the time
to stone passage from 11 to 5.2 d without any significant side effects (18). The mecha-
nism proposed for β-blockers is also ureteral smooth muscle relaxation.
Miscellaneous Agents Studied in Conservative Stone Management
Metoclopramide has been prospectively compared in 21 patients to opiates for relief
of pain caused by ureteral colic (19). The pain relief at 10, 20, and 30 mins after treatment
was thought to be comparable to opiates in this small group.
Glyceryl trinitrate (GTN) patches, 5 mg, identical to those used for patients with
cardiac angina, have been studied in acute ureteral colic. In a preliminary study of
various routes of administration of GTN in patients with ureteral colic, Hofstetter and
Kriegmair found GTN to be beneficial (20). However, in a well designed, randomized,
double-blinded study of 50 patients with under 10 mm stones, GTN did not demonstrate
any advantage in stone-free rate, interval to stone passage, or number of episodes of pain
over placebo (21).
Chapter 24 / Management of Ureteral Calculi 461
Rowatinex, an oral medication of essential plant oils produced in Ireland, has been
evaluated for its value in urolithiasis. In a prospective placebo controlled trial of 87
patients with ureteral stones, the overall stone expulsion rate was significantly higher
in the Rowatinex group as compared to placebo: 81% and 59%, respectively (22). The
mechanism of action is unknown.
Because the ureteral dilation seen in pregnant women is likely caused by progester-
one, it has been proposed as a treatment for ureterolithiasis (23). Mikkelson et al. gave
24 patients with ureterolithiasis an IM injection of 250-mg hydroxyprogesterone and
observed spontaneous stone passage in 75% of the new patients within 3 wk and claim
this is superior to traditional control groups. Progesterone agents have not been studied
in a well-designed, controlled study.
High Water Intake
Although increased fluid intake has been shown to be effective at diminishing stone
recurrence rates, the utility of high fluid intake to improve stone passage is controversial.
High fluid intake is commonly recommended in order to “flush” the stone out, but these
instructions have little physiologic basis. The response to unilateral partial obstruction
is an initial increase in renal blood flow and glomerular filtration rate and a subsequent
decrease in both with continued obstruction. Ureteral pressure initially increases and
stabilizes as ureteral coaptation is lost with progressive ureteral dilation. Initially, ure-
teral parastalsis increases but then decreases over time in the face of obstruction (25).
Therefore, after ureteral obstruction reaches a steady-state, increases in oral or intrave-
nous fluids are not likely to affect the pressure in the obstructed kidney. Indeed, in cases
of partial obstruction where ureteral peristalsis and coaptation is maintained, increasing
fluid intake may drive the obstructed kidney to lose ureteral coaptation, thus worsening
stone progression. It has been observed that when obstruction is relieved by percutane-
ous nephrostomy drainage, stone passage is enhanced, also arguing against the value of
increased fluid intake during an acute stone episode. Additionally, in an animal model,
percutaneous nephrostomy drainage was shown to be superior to stenting for spontane-
ous stone passage (26).
Supporting increased fluid intake to enhance ureteral stone passage is a recent article
by Kaid-Omar et al. (27). In a nonrandomized observation study, 219 patients with
ureteral stones under 6 mm were offered an intensive regimen of oral fluid intake. One
hundred twenty-nine patients agreed to drink 3 L a day and 90 declined. The patients with
high fluid intake had a greater stone passage rate (76% vs 14%, p < 0.001). They also had
a significant increase in their urinary pH and a decreased stone recurrence rate. An
obvious shortcoming of the study is the lack of randomization and the resulting potential
for selection bias.
RENAL INJURY DURING PERIODS OF OBSERVATION
Limiting potential renal injury is an important goal in the management of ureteroli-
thiasis. There is evidence that irreversible renal injury can occur with long periods of
ureteral obstruction. The challenge is defining the degree of obstruction and deciding
when to intervene. A historical method is to assign degree of obstruction based on the
delay of the nephrogram and excretion of contrast on intravenous pyelography. Another
method is to perform nuclear scintigraphy to assess degree of obstruction based on the
excretion of radiopharmaceutical. Both methods are flawed because they represent a
462 Kane
narrow observation of a phenomenon which is in flux. Many patients go from significant
obstruction to minimal obstruction or stone passage within days. Degree of pain is also
not a reliable indicator of degree of obstruction and we found that pain was not highly
correlated to stone passage success or interval (3).
The safe interval of observation is also not known. Holm-Nielsen et al found that a
third of patients with unilateral ureteral obstruction lasting over 1 mo suffered irrevers-
ible renal injury that was difficult to predict based on clinical or radiographic data (28).
Irving et al. recently studied 54 patients with symptomatic unilateral ureterolithiasis with
mercapto-acetyltriglycine radioisotope renography to monitor renal function (29). They
performed renal scans within 48 h of presentation, and again after stone treatment or 1 mo
if treated conservatively. They intervened on any kidney whose differential function was
under 45% (15 patients, 28%). When they compared the recovery of function of the 11
patients who had intervention in fewer than 7 d to the 4 patients whose intervention was
after 7 d, the early intervention group had better recovery of function. A limitation of the
study is that some of the patients who had intervention for diminished function likely
underwent unnecessary intervention and would have passed the stones and had sponta-
neous recovery of function. These authors argue for nuclear renography and observation
only for those patients with over 45% differential renal function.
OBSERVATION IN CHILDREN
There are few recent reports of the success of observation on ureteral calculi in
children. Van Savage et al recently reviewed the outcome of 33 children with ureteral
stones (30). Twelve patients (36%) passed the stones spontaneously. The average size
of the stones which passed was 2 mm whereas no stone over 4 mm passed spontaneously.
This supports observation as a reasonable initial strategy for children with small distal
stones and well controlled pain. The AUA clinical guidelines for ureteral stones are
reasonable for children although the impact of stone size on particular treatments may
need to be adjusted depending on the size of the child.
COST
The cost of conservative management of ureteral stones is multifactorial and com-
plex. The obvious direct costs include the cost of outpatient visits, follow-up laboratory
tests, radiographs, medications and emergency department visits. Indirect costs include
lost wages from missed work and decreased work productivity caused by the effects of
pain medication. The total cost of urolithiasis care is increased with the inappropriate
attempt at observation for stones destined to require intervention. In a decision analysis
model, Lotan et al found observation to be the least costly strategy of ureteral stone
management if no costs, such as from emergency department visits, was incurred
because of failed observation (31).
INDICATIONS FOR INTERVENTION
Initial management of ureteral calculi should be based on patient history, comorbidi-
ties, symptoms, renal function, and stone size and location on imaging. Patients with
solitary kidneys or bilateral ureteral stones require intervention and are poor candidates
for observation. Similarly, patients with evidence of urinary infection in the face of a
ureteral calculus are best managed with percutaneous nephrostomy or ureteral stenting
and antibiotics before definitive management. Patients with normal renal function and
Chapter 24 / Management of Ureteral Calculi 463
ureteral stones under 6 mm should be considered for observation. Those with stones that
are smaller and more distal are more likely to pass spontaneously. Miller and Kane found
that 50% of patients with over 4 mm stones ultimately fail conservative management (3).
In our series, the most common reason for intervention was poor pain control followed
by nonprogression after an adequate period of observation. Patients considering obser-
vation need to allow from 2 to 4 wk in order to give an adequate trial of intervention.
Indications for intervention during that time include poor pain control, inability to tol-
erate oral pain medication, urinary infection, repeated emergency room visits, non-
progression on serial imaging, or a social situation which does not allow missed work
or oral narcotics. Common professions that are poorly compatible with observation are
physicians, pilots, and attorneys.
CONCLUSIONS
Conservative management is the preferred strategy for most patients with ureteral
stones under 4 mm and should be considered for select patients with ureteral stones up
to 8 mm in size. The likelihood of success diminishes as the size of the stone increases
and for more proximal stones. Good pain control is critical for patient acceptance of
observation. Serial monitoring should take place with clinical and radiographic assess-
ment to ensure stone progression. There is strong evidence that oral calcium channel
blockers and oral steroids may decrease patient pain and decrease the time interval of
stone passage. Longstanding high-grade obstruction can contribute to irreversible renal
injury; therefore vigilant follow-up of ureteral calculi is warranted with intervention for
over 2 wk of high-grade obstruction or for nonprogression.
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