Marshall L. Stoller, Maxwell V. Meng-Urinary Stone Disease
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20 Master, Meng, and Stoller
dissolve vesical calculi by medication (Mrs. Stephen’s Cure for the Stone) (37). This
concoction of hers, containing crushed eggshells, snails, and soap, had many famous
advocates and an equal number of detractors. Such was the magnitude of the problem in
18th century England that a grateful Parliament awarded her 5000 pounds, a princely
sum in that era. In summary, medications of this class mainly contained lime as the active
ingredient and worked far better in vitro than in vivo, as a result this kind of “remedy”
fell into disuse.
Upper Urinary Tract
IMAGING
Imaging instruments have been critical in making diagnosis of urinary calculi. The
first seminal event was the introduction of the X-ray. Roentgen introduced imaging
technology on November 8, 1895, calling the source of energy “X-rays” because of their
unknown origins, although they were then identified as high-energy electromagnetic
radiation, which gave physicians a noninvasive method of looking for suspected urinary
calculi. The first radiograph showing a renal calculus was obtained by a Scottish phy-
sician (otolaryngologist), John Macintyre in 1896. Specific anatomic detail as well as
functional dynamic activity of the urinary tract was made possible by the synthesis of an
iodinated compound, uroselectan, by Moses Swick and others in 1928 (38,39). The
ultimate imaging “instrument” impacting urological surgery was the advent of CT scan-
ning in the 1970s (40). Interestingly, in this landmark article, although calculi are clearly
identified, the authors state, “The clinical merit of this observation [finding calculi] is
presently unknown.”
Fig. 11. Bellows designed for the administration of lithotriptic bladder irrigation solution.
Chapter 1 / Stone Nomenclature and History 21
DIAGNOSTIC APPLICATIONS
Endoscopic evaluation of the upper urinary tract was an act of serendipity (41). It was
first performed using a 9.5-Fr pediatric cystoscope in 1912 and reported in 1929 by Hugh
Hampton Young and Robert W. McKay (42). His description of this procedure, per-
formed in a 2-mo-old child with massively dilated ureters secondary to posterior urethral
valves, is succinct and illuminating, “In one case in which it was possible to introduce
the cystoscope into a dilated ureter, we were able, by using the extra-long straight
cystoscope, which is employed in Young’s cystoscopic lithotrite, to introduce the cys-
toscope to the pelvis of the kidney, and when withdrawn the greatly dilated ureter with
its convolutions and tortuosities and valvelike septa were seen.” However, it was not
until 1977 that the development and use of routine rigid ureteroscopy was reported by
E. S. Lyon and by T. M. Goodman. Lyon performed distal ureteroscopy in four women,
including ureteroscopic resection, after dilation of the ureteral orifice up to 16 Fr with
Jewett sounds, simultaneously passing the sound alongside a pediatric cystoscope
through the female urethra. Once the orifice was dilated, an 11-Fr cystoscope or 14-Fr
resectoscope was used. An average of 4 cm of distal ureter could be visualized in this
fashion. Goodman, who performed ureteroscopy in two men and one woman, did not
dilate the orifice, but on one occasion did create a ureteral meatotomy to achieve access
to ureteral tumor to cauterize it. He was actually able to fulgurate a ureteral tumor in this
fashion, thereby using ureteroscopy as a therapeutic tool for the first time (43,44). With
the development of the rod lens system by Harold Hopkins in 1960, smaller diameter
ureteroscopes could be constructed that have improved optical clarity and allow for the
introduction of working channels. The rod lens system was also marked by having
increased durability, a problem that plagued early ureteroscopes. The first rigid urologic
endoscope used in clinical practice was made by Wolf and its use was reported in 1979.
This instrument had a working length of 23 centimeters, as it was based on the design
of a pediatric cystoscope, and sheath sizes from 13 to 16 Fr. The size of this instrument
allowed for the directed ureteroscopic extraction of calculi for the first time (45). The
rapid introduction of longer (39 cm) and narrower (9 Fr) rigid ureteroscopes soon fol-
lowed, which allowed for instruments to reach into the renal pelvis (46).
It is interesting that the introduction of flexible ureteroscopy and its publication
actually predated rigid ureteroscopy. V.F. Marshall first performed flexible ureteropy-
eloscopy in 1960 by introducing a 9-Fr ureteroscope through a ureterostomy into the
renal pelvis to visualize stones. Subsequently, his associates used this instrument placed
through a 26-Fr cystoscope to visualize a left ureteral stone 9 cm from the ureteral orifice
(35). This instrument was not capable of directed deflection and was only used diagnos-
tically (Fig. 12). With increasing improvements in fiberoptic technology, a small-caliber
2-mm-tipped actively deflectable 70-cm ureteroscope was used by Takagi and col-
leagues to perform transurethral ureteroscopy, including visualization of the renal pelvis
and calyces. This instrument did not have an irrigation channel so visualization was often
impaired as surgeons relied on mannitol-induced forced diuresis (47,48).
T
HERAPEUTIC INSTRUMENTATION
Intracorporeal Instrumentation
Electrohydraulic lithotripsy (EHL) was the first use of a shock wave in a liquid
medium for the fragmentation of urinary stones. It was invented in 1955 by L. A. Yutkin,
a Russian engineer. Unfortunately for patients, he was a victim of Stalinist persecution
22 Master, Meng, and Stoller
and was banished for 10 yr, thus delaying the clinical introduction of this technology.
EHL essentially functions as an underwater spark plug producing both a powerful
shock wave and a cavitation bubble when the device is about 1 mm away from a stone.
Later, the physicist Jutkin in Leningrad showed that underwater electrical discharges
between electrode tips could destroy plates of china (49). His colleague, Goldberg, a
urologist from Riga, used electrohydraulic shock waves, delivered via a cystoscope, to
destroy a bladder stone in a patient. It was quickly used to treat ureteral calculi as well.
In 1978, Raney used a 9-Fr EHL probe to blindly fragment distal ureteral stones suc-
cessfully (50).
Other intracorporeal stone fragmentation instruments were being developed at ap-
proximately the same time. Ultrasound was first used experimentally for fragmenting
urinary stones by William P. Mulvaney in 1953 (51). This device consisted of a metal
probe attached to a piezoelectric plate. When electric current was delivered to the plate,
the tip vibrated and resulted in stone fragmentation and also heat production, which
caused thermal damage. The final advance in this instrument was a combination of
irrigation, coupled with suction, so that heat buildup would not occur.
The ruby laser was developed in 1960 and was able to fragment urinary calculi, but
produced unacceptable thermal tissue damage (52). Many other lasers were used, includ-
ing the clinical use of the flashlamp-pumped tunable dye laser. The laser most used for
urinary stone disease is currently the Holmium:YAG laser because of its versatility and
cost-effectiveness (53).
Fig. 12. Flexible ureteroscope designed by V. F. Marshall. Note the lack of an irrigating channel.
Chapter 1 / Stone Nomenclature and History 23
Extracorporeal Instrumentation
The first attempts to disintegrate human calculi by acoustic energy (extracorporeal
shock wave lithotripsy [SWL]) used a setup without direct contact between the trans-
ducer and the stone surface, and the first reported fragmentation of biliary calculi in an
in vitro model appeared in 1950 from Harold Lamport and Herbert Newman. Urinary
calculi could not be fragmented with this particular noncontact setup. Finally, an in vitro
contact-free approach combined with pulsed acoustical energy was derived using an
electrode-ellipsoid system by Lamport and Newman in the 1950s (49). Later, the Ger-
man aerospace firm Dornier developed an interest in understanding the effects of shock
waves, which was prompted by observations of aircraft metal fatigue as well as shock
wave-related injuries sustained by tank crews struck by shells. Experimentally, focused
shock waves were created by an underwater spark discharge. Dornier scientists discov-
ered that when metallic spheres were bombarded with shock waves, small pit marks
would appear beneath water droplets on the sphere’s surface. Sometime later, a Dornier
engineer experienced a sensation similar to an electrical shock when he touched a target
body at exactly the same moment that it was hit by a high-velocity projectile, although
unlike an electrical shock, his skin was not injured at the point of contact (54). As the
story goes, the wife of one of these engineers suggested studying the effect of shock
waves on kidney stones (55). In the 1970s a research program in Munich, led by F.
Eisenberger and C. Chaussey, showed that shock waves could be created and passed
through biologic media without causing harm. Dogs were implanted with urinary stones
and then successfully treated. The first human was treated in 1980 using the Dornier HM-
1 (Human Machine-1). The first reports describing this technology by Chaussey and
colleagues for successful clinical use appeared in 1980 (56,57). The first commercial
lithotriper was the HM-3, which was produced in 1984. Further refinements in this
instrument have been directed at producing machines that produce weaker shock waves
so that less anesthesia is necessary, as well as making machines portable. More detailed
accounts of the interesting development of SWL are found elsewhere (55,58).
Percutaneous
Willard E. Goodwin first reported the use of percutaneous trocar nephrostomy in 1955
using static X-ray images and 12-gauge needles with polyethylene tubing for drainage
(59). With this enormous advance, a Swedish team including a urologist B. Johannson
and a radiologist, I. Fernstrom, performed the first percutaneous nephrolithotomy in
1973, and reported it in 1976 (60). This was a heroic undertaking, lasting approx 2 wks,
quite unlike the percutaneous single-stage procedures of today. After the initial needle
placement into a “strategically chosen calyx,” increasingly larger semirigid polypropy-
lene tubes were placed as dilators. These tubes were warmed over steaming water gen-
erated by a teapot to make them malleable and were upsized every other day. In this way,
it took 10–14 d of successive dilations to create a 20-Fr channel. After this, a Dormia
basket was inserted and the stone removed under fluoroscopic guidance. Subsequent
modifications in instrumentation followed because of the variable shape of stones,
requiring, on occasion, the local silversmith to make forceps of the requisite shape. The
potential power of this technology was advanced quickly in the early 1980s by P. Alken
and Michael Marberger in Germany, by J. E. A. Wickham and Ronald A. Miller in
England and by Joseph W. Segura and Ralph V. Clayman in the United States (61). The
end result of a great deal of effort was to create the ability to widen tracts in a single
session and to remove stones under direct vision, including the use of flexible
24 Master, Meng, and Stoller
nephroscopy. Essentially by a process of steady miniaturization, instrumentation and
techniques used in the lower urinary tract, such as litholopaxy using ultrasonic disinte-
gration and EHL, were then used successfully in the upper tracts (62).
Laparoscopic
Laparoscopy was first performed in 1901 to observe the effect of pneumoperitoneum
on the abdominal organs. Georg Kelling (1866–1945), a surgeon from of Dresden,
introduced a Nitze cystoscope into a dog’s abdominal cavity and found with pressures
of 100 mmHg organs were smaller and colorless. He attempted to use it on two patients,
one of whom was having an intraabdominal hemorrhage, which he thought he could
arrest with “lufttamponade” (pneumoperitoneum). The patients refused and it was a
further 9 yr before the first clinical use in a human by Hans Christian Jacobaeus (63).
During the 1960s gynecologists began to carry out small surgical interventions on a
regular basis, which mainly consisted of endoscopic sterilization first performed by R.
Palmer of Paris. Kurt Semm, a gynecologist, performed the first laparoscopic appendec-
tomy in 1980. The pace of introduction and implementation of this instrumentation was
rapid. In September 1985, Erich Muhe, a general surgeon from Germany, used Semm’s
instruments to remove the first gallbladder in the world laparoscopically (64). The first
major solid organ to be removed was performed by Ralph Clayman and colleagues, who
performed a right laparoscopic radical nephrectomy (65).
The use of laparoscopic instrumentation for ureterolithotomy was first reported by
John Wickham in 1979 (66). Incidentally, it was Wickham who first coined the term,
“minimally invasive surgery” (64). Laparoscopic instrumentation for ureterolithotomy
was used as an alternative to open surgery in the setting of a salvage procedure after failed
shock wave lithotripsy or endoscopic procedures.
It is fascinating to examine the “cross-pollination” of different surgical specialties in
advancing instrumentation. For example, the cystoscope was used for thoracoscopy.
Surgeons then used the thoracoscope therapeutically to release pleural adhesions, which
provided impetus to perform transurethral procedures. Laparoscopic instrumentation
designed for relatively simple gynecologic operations like tubal ligation was modified
and advanced for extirpative general surgical procedures like cholecystectomy and
finally to major organ removal like nephrectomy and ultimately to laparoscopic recon-
structive surgery like pyeloplasty. Similarly, the first cardiac catherization experiment
was performed by Werner Forssmann using a ureteral catheter to place into his own left
arm vein (15).
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27
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
2
Epidemiology and Incidence
of Stone Disease
Joseph E. Dallera, MD
and Paramjit S. Chandhoke, MD, PhD
CONTENTS
TYPES OF STONES
INCIDENCE, PREVALENCE, AND LIFETIME PREVALENCE
AGE, SEX, AND RACE
RISK FACTORS FOR STONE DISEASE
PEDIATRIC STONE DISEASE
PREGANCY
STONE DISEASE IN PATIENTS WITH SPINAL CORD INJURY
RECURRENCE FOLLOWING SWL
R
EFERENCES
Key Words: Epidemiology; nephrolithiasis; incidence.
TYPES OF STONES
Urinary stones are polycrystalline aggregates consisting of varying amounts of crystal
and organic matrix components. Although urolithiasis is inclusive of renal, ureteral, and
bladder stones, the following discussion will pertain only to symptomatic renal and
ureteral stones, as they are the most common. The most common urinary stone types are
calcium oxalate, calcium phosphate, uric acid, struvite (magnesium ammonium phos-
phate), and cystine. In an analysis of 14,557 renal and ureteral stones, 52% were purely
calcium oxalate, 13% purely calcium phosphate, 15% a mixture of calcium oxalate and
phosphate, 4% struvite, 8% uric acid, and 8% other compounds (1). As the majority of
stones are of the calcium variety, it is likely that most epidemiological studies of neph-
rolithiasis pertain to this compositional form. Of the less common stone varieties, struvite
stones are commonly associated with urinary tract infections, most notably secondary to
urease splitting organisms such as Proteus and Klebsiella. Uric acid stones, associated
with hyperuricosuric patients, are found in patients with gout, dehydration, and exces-
28 Dallera and Chandhoke
sive purine intake. Finally, cystine stones are a rare form associated with inborn errors
of metabolism resulting in abnormal absorption of dibasic amino acids in the small
bowel and proximal renal tubule.
A more recent variety of urolithiasis is found secondary to treatment with indavir, a
protease inhibitor used as a primary treatment for the human immunodeficiency virus (2).
Indavir was approved by the Federal Drug Administration in 1996 and is formulated as
a sulfate salt. It has been reported that as much as 20% of the drug is excreted unchanged
in the urine (3). Compositional analysis of indavir stones often reveal pure Indavir, but
may also include other constituents such as calcium oxalate. The significance of this
compositional variance, in contrast to all other stone types, is that pure indavir stones may
not be visible on noncontrast computed tomography scans (4). In a recent study of 105
patients undergoing treatment with indavir for 1 yr, a stone incidence of 12% with a
median duration of time from treatment to acute stone episode of 22 wk was reported (4).
INCIDENCE, PREVALENCE, AND LIFETIME PREVALENCE
It is important to define the terms incidence, prevalence, and lifetime prevalence of
stone disease to ensure proper comparisons between epidemiological studies. The inci-
dence of stone disease is defined as the number of new stone patients in a given popu-
lation over a defined period of time (usually a year). Prevalence is defined as the number
of stones present in a screened population at a particular point in time. Finally, lifetime
prevalence is defined as the presence of a stone at any point in a patient’s history.
Therefore, surveys that ask if a person has “ever had a kidney stone” imply a lifetime
prevalence of urolithiasis.
In a 25-yr study of the incidence of stone disease from 1950 to 1974 among the
population in Rochester, MN, the overall rate for males was 109.5 per 100,000 and the
rate for females was 36.0 per 100,000 (5). In a more recent prospective study by Curhan
et al., the incidence of stone disease was found to be 300 per 100,000 in males and 100
per 100,000 in females (6,7). This suggests a possible increase in the incidence of stone
disease over the last three decades. In an Italian study conducted between 1993 and 1994,
the incidence was calculated at 168 per 100,000 inhabitants (8). Finally, a Japanese study
determined the incidence of stone disease in 1995 to be 100.1 per 100,000 for males and
55.4 per 100,000 for females (9). In comparison to a similar study conducted in 1965
(81.3 per 100,000 for males and 29.5 per 100,000 for females), Yoshida et al. concluded
that there was a steady increase in the annual incidence of stone disease in Japan over
a 30-yr period (9).
Estimates of lifetime prevalence have been determined by several studies in the United
States. In a study by Soucie et al., the lifetime prevalence of stone disease was found to
be 10% for men and 4% for women (10). Similarly, a study by Curhan et al. found a
lifetime prevalence of 8.7% in men (6). However, in considering lifetime prevalence of
stone disease, it is necessary to discuss variations based on gender, race, geography, and
diet. These factors will be discussed subsequently.
AGE, SEX, AND RACE DEPENDENCE
Symptomatic calcium stone disease is most common from the third to sixth decades
of life. However, variations are evident depending on gender and stone type. In a 25-yr
study of the population of Rochester, MN, the incidence of stone disease in men
increased significantly after the age of 35, most notably between the ages of 50 and 70.
Chapter 2 / Epidemiology of Stone Disease 29
In women the rate remained relatively constant over the entire 25-yr period (5). Therefore,
the overall male to female ratio of the incidence of stone disease increased from 1.8:1 to
3.8:1 over the entire study period. With respect to age, men and women have a similar
incidence of stone disease during early life (second and third decades) and late life (sev-
enth decade and older) (11). However, between the third and seventh decades of life, men
have an incidence of symptomatic stones two to five times that of women. It should be
noted that these figures pertain to symptomatic kidney and ureteral stones as the preva-
lence and age frequency of asymptomatic stones is unknown. It is possible that the
incidence of asymptomatic stone disease is similar between men and women (12).
Epidemiological studies of the lifetime prevalence of stone disease have been con-
ducted primarily within the Caucasian population. Several studies among the African
American, Hispanic, and Asian populations, however, suggest the male predominance
of stone disease may not be maintained outside of the Caucasian population. In a study
of 444 patients with stone disease in 1994, women made up 68% and 62% of the African
American and Hispanic stone populations, respectively (13). Another racial comparison
study revealed that African American men have a 0.4, Hispanic men a 0.66, and Asian
men a 0.56 lifetime prevalence of stone disease relative to Caucasian men (10). In
comparison to Caucasian women, African American women were found to have a 0.61,
Hispanic women a 0.85, and Asian women a 0.54 relative lifetime prevalence of stone
disease (10).
RISK FACTORS FOR STONE DISEASE
Climate and Geography
Many epidemiological studies have recorded a geographic variability in the preva-
lence of stone disease. It has been postulated that this variability may be owing to
variations in climate and sun exposure, although others have questioned the role of diet
and water quality as well. The most convincing evidence to date, however, reveals
temperature and sun exposure to play important roles in the geographic variability of
stone disease. It is believed that individuals living in hot climates have an increased
lifetime prevalence of stone disease secondary to dehydration. Further, individuals liv-
ing in areas with increased sun exposure are likely to have absorptive hypercalciuria
secondary to elevated vitamin D synthesis. In a 1994 study by Soucie et al., the lifetime
prevalence of stone disease increased in the United States from north to south and west
to east (10). Further, it was determined in a later study that correction for ambient
temperature, sunlight, and consumption of several beverages eliminated the geographic
variation in lifetime prevalence of stone disease (14). In contrast, a recent study of 1179
postmenopausal women with stone disease found no association between temperature
and stone disease (15). Therefore, other factors likely play an important role in the
geographic variability of stone disease and must be considered.
Similar to geographical location, a person’s occupation may influence their risk for
nephrolithiasis. As warm climates seem to predispose to stone formation, so do occupa-
tions involved with warm working environments. However, the situation of occupation is
independent of the effects of sun exposure and vitamin D synthesis. Epidemiological
studies have shown an increased risk of stone disease in cooks and machinists. A 1993
study of machinists working in a hot environment revealed a prevalence of 8.5% compared
with age- and sex-matched controls working in a normal temperature, which had a preva-
lence of 2.4% (16). Not surprisingly, uric acid stones were the most common stone type