Urologia Urol Int 2007;79(suppl 1):37
Internationalis DOI: 10.1159/000104434
Epidemiology and Risk Factors in
Urolithiasis
R. Bartoletti T. Cai N. Mondaini F. Melone F. Travaglini M. Carini M. Rizzo
Department of Urology, University of Florence, Florence, Italy
Key Words
Urinary stones, epidemiology  Risk factors, urinary stones 
Extracorporeal shock wave lithotripsy, residual fragments
Abstract
Stone formation in the urinary tract affects about 510% of
the population in industrialized countries, although it is very
rare in other countries such as Greenland or Japan. The high
incidence and recurrence rate contribute to making the uro-
lithiasis a serious social problem. Nowadays, urolithiasis
must be considered a disease in evolution for several rea-
sons, such as epidemiological changes, evolution of the
methods used for diagnosis, and the treatment and prophy-
laxis of the population considered at risk of stone disease.
Some features of stone disease have changed over the last
few years due to many social, economical and cultural fac-
tors that are described here. The increased prevalence of
small urinary calculi has brought about a change in clinical
symptoms, with frequent episodes of renal-ureteral colic,
persistent pain and hydronephrosis. Similarly, the presence
of residual fragments after extracorporeal shock wave litho-
tripsy has induced a radical change in the management of
small calculi through the use of mini-invasive surgical tech-
niques. Copyright 2007 S. Karger AG, Basel
2007 S. Karger AG, Basel
00421138/07/07950003$23.50/0
Fax +41 61 306 12 34
E-Mail karger@karger.ch Accessible online at:
www.karger.com www.karger.com/uin
Introduction
Stone formation in the urinary tract affects about 5
10% of the population in industrialized countries, al-
though it is very rare in Greenland or in Japan [1]. This
could be for various reasons, such as diet, climate, daily
water intake, physical activity and corporeal overweight
[2]. The annual incidence of stone formation is generally
considered to be 1,5002,000 cases per million [3]. Data
on the incidence of stone disease in Italy derive from a
national survey carried out by the National Institutes of
Statistics in 1994; the prevalence is 17.2% and a total so-
cial costs amount to EUR 150 million/year [4]. Urinary
calculi are commonly diagnosed as a consequence of an
episode of renal-ureteral colic or gross hematuria. Many
patients are diagnosed after an abdominal ultrasound
scan after reporting unrelated symptoms [5]. On the oth-
er hand, stone disease must be considered a disease in
evolution for several reasons, such as epidemiological
changes, advances in the methods used for diagnosis,
treatment and prophylaxis of the population considered
at risk of the disease.
Epidemiology
The risk of developing urinary tract stone disease in
normal adults varies in different countries in the world.
The probability of stone formation seems to be lower in
128.122.253.212 - 10/21/2014 10:52:20 PM
NYU Medical Center Library
Riccardo Bartoletti, MD
Department of Urology, University of Florence
Via dellAntella, 58
Downloaded by:
IT50011 Bagno a Ripoli, Florence (Italy)
Tel. +39 055 249 6301, Fax +39 055 249 6452, E-Mail riccardo.bartoletti@unifi.it
Asia (15%) than Europe (59%) and the USA (13%). The
highest risk is reported in Saudi Arabia (20.1%) [3]. In
recent years, the prevalence and incidence of urinary
stones has increased [2]. In Central Europe, the annual
prevalence of cases of stone disease gradually increased
from 5.9 to 9%, with an increase in the hospitalization
incidence from 0.049% in 1954 to 0.097% in 1974 [6]. In
1994, urinary stone prevalence increased to 17.2%, with
an incidence rate of 1.7% compared with other urological
diseases [4]. Moreover, in 1985 the cost of each incident
of stone disease in the USA was estimated to be USD
2,000. In 1993, the annual total cost for urinary stone
management increased to USD 315,000,000, showing
that urinary stone diseases are a real social and econom-
ic problem [7]. The epidemiology of stone disease differs
according to the geographical area and historical period.
Changing socioeconomic conditions have generated
changes in the incidence and type of stones in terms of
both site and the physical-chemical composition of stones
[1].
Stone Components
The main chemical component of stones is calcium
oxalate (5070%), either in its pure form (30%) or mixed
with calcium phosphate (40%) [1]. Other types of urinary
stones are uric acid (1020%), struvite (ammonium-mag-
nesium phosphate, 510%) and cystine (12%). Rarer
stones are made of silica and xanthine and 2,8-dihy-
droxyadenine [1]. Urinary calculi have changed in com-
position over the last few years, due to an increased rate
of calcium-oxalate (from 65 to 80%) in the urine, while
infection-related stone formation has decreased sharply
from 15 to 4% [8]. This could be due to both the higher
quality of life in developed countries and the widespread
use of antibiotics. The epidemiology of cystine stones has
not changed, because homozygous cystinuria persists in
a small proportion of the population [9]. The prevalence
of uric acid stones has also dropped from 15 to 8% [10];
the reduction could be related to the early identification
of patients metabolic alterations and controlled dietary
regimens in overweight patients [11].
Stone Size
In the last two decades, an increased rate of small ure-
teral stones has been found [12]. This phenomenon could
be due to the widespread use of extracorporeal shock
wave lithotripsy (ESWL), with subsequent reclamation of
large-sized renal calculi, and noninvasive diagnostic
techniques such as ultrasound and spiral computed to-
mography [13]. The increased prevalence of small uri-
4 Urol Int 2007;79(suppl 1):37
nary calculi (!1 cm) has changed the clinical symptoms,
with frequent episodes of renal-ureteral colic, persistent
pain and hydronephrosis [5], leading to a fundamental
change in disease management. Small calculi are often
removed by means of mini-invasive techniques such as
uretero-litholapaxy or uretrorenoscopy with intra-ure-
teral calculi fragmentation [5]. ESWL can still be used as
a first-step treatment option for distal ureteral or medi-
um-sized renal stones (between 0.5 and 2 cm) [5], while
percutaneous nephrolithotripsy should be reserved for
treating larger calculi [14]. A recent survey in Japan
showed that cases of bladder stone formation dropped
sharply from 50% in 1950 to !5% in 1985. The authors
suggested that the decrease in vesical stones is due to in-
creases in the dietary intake of animal proteins and ad-
vances in diagnostic technique performance [15]. The
modern urologist knows that the decrease could be due
to both a rational interpretation of urinary tract obstruc-
tive phenomena and a substantial reduction in malnutri-
tion throughout the world.
Risk Factors
Stone disease presents a complex model for interpret-
ing the mechanisms involved in its genesis and develop-
ment, as well as genetic, anatomic, nutritional, and envi-
ronmental factors together with the presence of concom-
itant diseases. Moreover, much evidence has recently
been provided on dietary factors, such as animal protein
consumption and daily caloric intake, related to an in-
creased risk of stone formation [15].
Age, Race and Sex
The prevalence of urinary stones varies according to
age. In subjects under 45 years old the prevalence is 0.58%,
while in those over 65 it is 4.7% [16]. This correlation is
probably due to the presence of comorbidities (obesity,
hypertension, hyperuricemia, etc.). In Italy, the male-fe-
male ratio is 2: 1, according to the probability of stone
formation [23]. Several studies have reported that uri-
nary stones are relatively rare in Native Americans, blacks
in Africa and America and native-born Israelis. Ethnic-
ity, however, turns out to be a secondary risk factor [16].
About 25% of the patients with urinary stones have a
family history of stone disease, showing that it may be the
result of a polygenic defect with partial penetrance [16].
In addition, it has been clearly demonstrated that familial
renal tubular acidosis is strong associated with nephroli-
thiasis in almost 70% of patients [17]. The fact that men
have a higher incidence than females is probably related
to sex hormones [18].
128.122.253.212 - 10/21/2014 10:52:20 PM
NYU Medical Center Library
Bartoletti/Cai/Mondaini/Melone/
Travaglini/Carini/Rizzo
Downloaded by:
 Climate and Seasons
Stone recurrence is higher in spring and summer than
in autumn and winter, probably due to low fluid intake
and low urinary output [19]. Another possible explana-
tion is high vitamin D plasma levels due to longer sun
exposure time. The effect of geography on the incidence
and prevalence of stone diseases may be indirectly due to
its effect on temperature [19]. High temperatures increase
perspiration insensibility which may result in more con-
centrated urine [20]. This event promotes urinary crys-
tallization and stone formation.
Dietary Habits
Nutritional risk factors have recently been described:
increased animal protein, calcium and oxalate intake as
well as a high calorie content in the diet [21]. The correla-
tion between calcium intake and stone formation risk
still needs to be demonstrated. A significant relationship
between body mass index and increased risk of stone for-
mation was recently demonstrated by Siener et al. [22] in
527 former stone patients. Other authors reported an in-
verse correlation between body mass index and patients
urinary pH [23]. In a recent randomized study, Borghi et
al. [24] confirmed the main value of a generous fluid in-
take.
Comorbidity
Cross-section studies have shown that nephrolithiasis
is more frequently found in hypertensive patients than in
normotensive subjects. Borghi et al. [25] demonstrated a
greater risk of stone formation in subjects with hyperten-
sion associated with excess body weight. Higher oxaluria
and calciuria as well as supersaturation of calcium oxa-
late and uric acid appear to be the most important factors.
Excess body weight and consumption of salt and animal
proteins may also play important roles [22]. The observa-
tion that stone disease does not occur among the inhabit-
ants of Greenland or in other populations with a high
intake of fish oil has stimulated the therapeutic use of
eicosapentaenoic acid as a measure to prevent stones [26].
The mechanism of action of this compound is assumed
to be reduced calcium excretion, probably through a di-
rect effect on membrane efflux in tubular cells. Recent
studies have demonstrated that a stressful life is associ-
ated with kidney stones, together with lower family in-
come, mortgage problems and emotional life events [27].
In addition, social class and occupation are related to a
higher urinary stone risk. Manual workers presented a
much lower frequency of urinary stones than profession-
al and managerial groups [28].
Epidemiology and Risk Factors in
Urolithiasis
Natural History
The natural history of urinary stone disease is char-
acterized by specific steps from the formation of Ran-
dalls plaques to renal colic [29]. An acute episode of
renal or ureteral colic is the result of a stone obstructing
the urinary tract. After formation the stone moves down
and can impact five locations in the urinary tract: the
calyx; ureteropelvic junction; the pelvic brim where the
ureter begins to arch over the iliac vessels posteriorly;
the posterior pelvis where the ureter begins to arch over
the pelvic vessels, and the ureterovesical junction [3].
The probability of impaction at these locations is subject
to stone size: stones smaller than 4 mm are spontane-
ously expelled [5]. After impact, the calculus could in-
crease in size and cause total urinary obstruction with
upper hydronephrosis and subsequent renal colic [30].
The spontaneous passage of a stone is due to several fac-
tors relating to stone size, location, and side. In a pro-
spective study, Miller and Kane [31] recently reported
that stone size is the most important factor in predicting
stone passage. Moreover, in 75 patients it was demon-
strated that 95% of stones of 24 mm pass spontane-
ously within 40 days, while only 50% of stones larger
than 5 mm are able to pass through the ureter [31]. How-
ever, Hubner et al. [32] reported that stone size is not an
independent factor in predicting stone passage through
the ureter. Moreover, Hubner et al. [32] highlighted the
fact that stone location is relevant in predicting success-
ful spontaneous passage: 71% of all distal ureter stones
pass into the bladder, while only 22% of all proximal
ureter stones can do so. More recently, in the AUA guide-
line on urinary lithiasis, Segura et al. [33] demonstrated
that stone passage is related to stone size and location.
The correct identification of factors affecting stone pas-
sage through the ureter should be taken into account
when planning treatment management and follow-up of
patients affected by urinary stones. The natural history
of stone formation, development and expulsion has
changed in recent years due to the substantial improve-
ment in noninvasive diagnostic procedures, such as ab-
dominal ultrasound or spiral computed tomography,
and a fine definition of risk factors in patients consid-
ered as recurrent stone formers. The population of
stone-forming patients was definitely characterized by
the ESWL era, the widespread use of ultrasound scan-
ning and antibiotics.
128.122.253.212 - 10/21/2014 10:52:20 PM
NYU Medical Center Library
Urol Int 2007;79(suppl 1):37 5
Downloaded by:
 Residual Fragments after ESWL
The major problem in evaluating the natural history
of urinary stones is recurrence. The average recurrence
rate is 31.550% after 5 years from the first episode and
more than 72% after 20 years [34]. ESWL was the usual
treatment for most patients with upper tract stones, show-
ing only a few side effects [5, 32]. A new concept, how-
ever, should be taken into consideration: asymptomatic
residual stone fragments [35]. A small percentage of pa-
tients are, in fact, immediately stone free after ESWL
treatment and as many as 85% of them are reported to
have residual fragments in the urinary tract a few days
after ESWL. Today residual fragments are a common,
still controversial problem [35]. The question is: are re-
sidual fragments really clinical insignificant? Several re-
ports have recently demonstrated that the presence of re-
sidual fragments is an independent predictive factor of
the recurrence risk especially after a long-term follow-up
[36]. Residual fragments act as sources for re-growth and
further stone formation. Moreover, other studies have
shown that residual fragment size is a major parameter to
be taken into consideration. The presence of residual
fragments after ESWL suggests that medical therapy af-
ter ESWL treatment is a considerable option to take up in
the management of patients affected by urinary lithiasis
[37]. Several authors have suggested that a correct meta-
bolic evaluation should be used in order to establish
which metabolic factors need to be changed so as to low-
er the recurrence risk [38]. The real role of metabolic eval-
uation in predicting the risk of recurrence is still contro-
versial. Increasing use of mini-invasive methods in the
treatment of both residual urethral stone fragments
(steinstrasse) and small calculi which have passed into
the ureter during the ultrasound monitoring period is, at
the moment, the gold standard treatment for urolithiasis,
with high patient compliance and quick resolution of up-
per urinary tract obstruction.

References

1 Ramello A, Vitale C, Marangella M: Epide-
miology of nephrolithiasis. J Nephrol 2000;
13(suppl 3):S45S50.
2 Trinchieri A: Epidemiology of urolithiasis.
Arch Ital Urol Androl 1996; 68:203249.
3 Amato M, Lusini ML, Nelli F: Epidemiology
of nephrolithiasis today. Urol Int 2004;
72(suppl 1):15.
4 Serio A, Fraioli A: Epidemiology of nephro-
lithiasis. Nephron 1999;81(suppl 1):2630.
5 Tiselius HG, Ackermann D, Alken P, Buck C,
Conort P, Gallucci M; Working Party on Li-
thiasis, European Association of Urology:
Guidelines on urolithiasis. Eur Urol 2001;40:
362371.
6 Menon M, Koul H: Clinical review 32: Cal-
cium oxalate nephrolithiasis. J Clin Endocri-
nol Metab 1992; 74:703707.
7 Litwin MS, Saigal CS, Yano EM, Avila C, Ge-
schwind SA, Hanley JM, Joyce GF, Madison
R, Pace J, Polich SM, Wang M; Urologic Dis-
eases in America Project: Urologic diseases
in America Project: analytical methods and
principal findings. J Urol 2005;173:933937.
8 Moe OW: Kidney stones: pathophysiology
and medical management. Lancet 2006;367:
333344.
9 Schwarz RD, Dwyer NT: Pediatric kidney
stones: long-term outcomes. Urology 2006;
67:812816.
10 Smith LH: The medical aspects of urolithia-
sis: an overview. J Urol 1989;141:707710.
11 Schlesinger N: Dietary factors and hyperuri-
caemia. Curr Pharm Des 2005; 11: 4133
12 Galvin DJ, Pearle MS: The contemporary
management of renal and ureteric calculi.
BJU Int 2006;98:12831288.
13 Yilmaz S, Sindel T, Arslan G, Ozkaynak C,
Karaali K, Kabaalioglu A, Luleci E: Renal
colic: comparison of spiral CT, US and IVU
in the detection of ureteral calculi. Eur Ra-
diol 1998;8:212217.
14 el-Nahas AR, Eraky I, el-Assmy AM, Shoma
AM, el-Kenawy MR, Abdel-Latif M, Mosbah
A, Abol-Enein H, Shaaban AA, Mohsen T,
el-Kappany HA: Percutaneous treatment of
large upper tract stones after urinary diver-
sion. Urology 2006;68:500504.
15 Taylor EN, Curhan GC: Effect of dietary
modification on urinary stone risk factors.
Kidney Int 2006;69:1093.
16 Curhan GC, Willett WC, Rimm EB, Stamp-
fer MJ: Family history and risk of kidney
stones. J Am Soc Nephrol 1997; 8: 1568
1573.
17 Hess B: Acid-base metabolism: implications
for kidney stones formation. Urol Res 2006;
34:134138.
18 Kato Y, Yamaguchi S, Kakizaki H, Yachiku
S: Influence of estrus status on urinary
chemical parameters related to urolithiasis.
Urol Res 2005;33:476480.
19 Parry ES, Lister IS: Sunlight and hypercalci-
uria. Lancet 1975;1:10631065.
20 Al-Dabbagh TQ, Fahadi K: Seasonal varia-
tions in the incidence of ureteric colic. Br J
Urol 1977;49:269275.
21 Siener R: Impact of dietary habits on stone
incidence. Urol Res 2006;34:131133.
22 Siener R, Glatz S, Nicolay C, Hesse A: The
role of overweight and obesity in calcium ox-
alate stone formation. Obes Res 2004; 12:
106113.
23 Taylor EN, Curhan GC: Body size and 24-
hour urine composition. Am J Kidney Dis
2006;48:905915.
24 Borghi L, Meschi T, Schianchi T, Briganti A,
Guerra A, Allegri F, Novarini A: Urine vol-
ume: Stone risk factor and preventive mea-
sure. Nephron 1999;81(suppl 1):3137.
25 Borghi L, Meschi T, Guerra A, Briganti A,
Schianchi T, Allegri F, Novarini A: Essential
arterial hypertension and stone disease. Kid-
ney Int 1999;55:23972406.
26 Yasui T, Tanaka H, Fujita K, Iguchi M, Kohri
K: Effects of eicosapentaenoic acid on uri-
nary calcium excretion in calcium stone
formers. Eur Urol 2001;39:580585.
27 Najem GR, Seebode JJ, Samady AJ, Feuer-
man M, Friedman L: Stressful life events and
risk of symptomatic kidney stones. Int J Epi-
demiol 1997;26:10171023.
28 Ekane S, Wildschutz T, Simon J, Schulman
CC: Urinary lithiasis: epidemiology and
physiopathology. Acta Urol Belg 1997; 65: 1
8.
29 Matlaga BR, Coe FL, Evan AP, Lingeman JE:
The role of Randalls plaques in the patho-
genesis of calcium stones. J Urol 2007; 177:
3138.
128.122.253.212 - 10/21/2014 10:52:20 PM

4138.
NYU Medical Center Library

6 Urol Int 2007;79(suppl 1):37 Bartoletti/Cai/Mondaini/Melone/

Travaglini/Carini/Rizzo
Downloaded by:
30 Travaglini F, Bartoletti R, Gacci M, Rizzo M:
Pathophysiology of reno-ureteral colic. Urol
Int 2004;72(suppl 1):2023.
31 Miller OF, Kane CJ: Time to stone passage
for observed ureteral calculi: a guide for pa-
tient education. J Urol 1999; 162:688690.
32 Hubner WA, Irby P, Stoller ML: Natural his-
tory and current concepts for the treatment
of small ureteral calculi. Eur Urol 1993; 24:
172176.
Epidemiology and Risk Factors in
Urolithiasis
33 Segura JW, Preminger GM, Assimos DG,
Dretler SP, Kahn RI, Lingeman JE, Macaluso
JN Jr: Ureteral Stones Clinical Guidelines
Panel summary report on the management
of ureteral calculi. The American Urological
Association. J Urol 1997;158:19151921.
34 Skolarikos A, Alivizatos G, de la Rosette J:
Extracorporeal shock wave lithotripsy 25
years later: complications and their preven-
tion. Eur Urol 2006;50:981990.
35 El-Nahas AR, El-Assmy AM, Madbouly K,
Sheir KZ: Predictors of clinical significance
of residual fragments after extracorporeal
shockwave lithotripsy for renal stones. J En-
dourol 2006;20:870874.
Urol Int 2007;79(suppl 1):37
36 Osman MM, Alfano Y, Kamp S, Haecker A,
Alken P, Michel MS, Knoll T: 5-year-follow-
up of patients with clinically insignificant
residual fragments after extracorporeal
shockwave lithotripsy. Eur Urol 2005; 47:
860864.
37 Candau C, Saussine C, Lang H, Roy C, Faure
F, Jacqmin D: Natural history of residual re-
nal stone fragments after ESWL. Eur Urol
2000;37:1822.
38 Tailly GG: Modern approach to ureteral
stones. ScientificWorldJournal 2003; 3: 853
866.
128.122.253.212 - 10/21/2014 10:52:20 PM
NYU Medical Center Library
7
Downloaded by: