WHAT’S KNOWN ON THIS SUBJECT: Flank pain, hematuria, and dysuria are considered the warning signs of urinary tract involvement in children with RAP.
WHAT THIS STUDY ADDS: In children with RAP and urolithiasis, hematuria and dysuria are inconstant, and in children younger than 8 years of age, the abdominal pain is often central/diffuse. Infrequent pain attacks and a family history of urolithiasis are additional warning signs of urinary stones.
OBJECTIVE:Our goal was to establish the clinical presentation and features of pain attacks in children with recurrent abdominal pain (RAP) and urolithiasis.
METHODS:We compared the rate of previous appendectomy among 100 consecutive patients with that of 270 control subjects. We also compared the frequency of pain attacks with that reported by children with functional or organic gastrointestinal RAP.
RESULTS:Fifty-three patients had no history of dysuria or gross hema-turia, and only 35 had hematuria at the ﬁrst visit; 41 patients were evaluated for urolithiasis only because of a family history of kidney stones associated with RAP. Twenty-nine patients had been previously hospitalized for abdominal symptoms. Sixteen patients and 4 control
subjects (1.5%) had undergone a previous appendectomy (P⬍.0001).
Two to 28 months before the diagnosis of urolithiasis, 37 patients underwent abdominal ultrasonography, which did not show urinary stones. Sixty-nine percent of subjects younger than 8 years of age had central/diffuse abdominal pain. The mean frequency of pain attacks was 4 to 9 times lower than in patients with functional or organic gastrointestinal RAP.
CONCLUSIONS:Because of the inconstant occurrence of dysuria and hematuria, the location of pain in areas other than the ﬂank, and the lack of calculi shown on imaging studies performed after pain attacks, the urologic origin of pain may be overlooked and ineffective proce-dures performed. The possibility of urolithiasis should be considered in children with RAP who have a family history of urolithiasis and/or infrequent pain attacks, even when dysuria and hematuria are lacking,
and in younger children even when pain is not lateral.Pediatrics2009;
AUTHORS:Cesare Polito, MD,aAngela La Manna, MD,a
Giuseppe Signoriello, MD,band Antonio Marte, MDa,c
Departments ofaPediatrics,bPublic Health, andcPediatric
Surgery, Second University of Naples, Naples, Italy
urolithiasis, hematuria, dysuria, recurrent abdominal pain
RAP—recurrent abdominal pain
Accepted for publication Jun 12, 2009
Address correspondence to Cesare Polito, MD, Second University of Naples, Department of Pediatrics, Via L. De Crecchio 2, 80138 Naples, Italy. E-mail: email@example.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2009 by the American Academy of Pediatrics
Abdominal pain is the presenting symptom in 50% to 76.9% of children
with urolithiasis,1–5and it may occur as
acute/subacute or recurrent
abdomi-nal pain (RAP).3,6,7 RAP is common
among children and adolescents and
has been associated with⬎100
differ-ent conditions.6,8In most cases,
how-ever, no organic disease can be found, and most episodes of RAP are consid-ered to be a functional disorder that
affects gastrointestinal motility6,8and
is often associated with emotional
Pediatric urolithiasis is associated with signiﬁcant morbidity, particularly because stones tend to recur; thus, its occurrence should not be underesti-mated. Identiﬁcation of the clinical hallmarks of urinary tract involvement is crucial in selecting those children with RAP who require focused evalua-tion of the urinary tract. The locaevalua-tion of pain in the ﬂank as well as hematuria and dysuria are considered the only warning signs indicating more depth investigation of urinary tract
in-volvement in children with RAP.6,10To
date, no study has addressed the fre-quency of pain attacks in children with urolithiasis.
Here we report the results of an obser-vational study on children with RAP and urolithiasis. The goal was to as-sess the frequency and location of pain attacks, the occurrence of hematuria and dysuria, the rate of previous incon-clusive hospitalizations for abdominal symptoms, and the rate of appendec-tomy, which may reﬂect failure to de-tect the urologic cause and depict the severity and costs of RAP.
In 1999, we began a prospective obser-vational study of the clinical presenta-tion and outcome of children with uri-nary solute excretion abnormalities leading to urolithiasis. Some of the ﬁndings on participants with
hypercal-ciuria and/or hyperuricosuria, most of whom had no urinary stones, have
We evaluated 100 white patients aged 3 to 18 years with RAP who were ﬁrst diagnosed as having urolithiasis and were consecutively observed from Oc-tober 1, 1999, to November 14, 2008, in our clinical setting, which is mainly de-voted to pediatric nephrology/urology patients, but also cares for general pe-diatrics patients and lacks emergency service. Urolithiasis was deﬁned as im-aging identiﬁcation of a calculus or documented calculus passage. Mictur-ating cystography was performed on children with recurrent urinary tract infections or pathologic ultrasound ﬁndings, such as hypoplastic or dys-morphic kidneys or hydronephrosis, to determine the vesicoureteric reﬂux. Tc99m MAG3 dynamic renal scintigra-phy was performed on children with hydronephrosis to determine uretero-pelvic obstruction. We did not system-atically search for other possible causes of RAP. However, we excluded subjects with another potential source of RAP, as well as those whose report of symptoms was unreliable. Data col-lection was prospective and formed the basis of this observational study. We obtained approval from our institu-tional ethics committee, as well as signed informed-consent forms from the children’s parents.
RAP was deﬁned as at least 3 episodes of diffuse or localized abdominal pain
over a period of at least 3 months.13
The basic investigation protocol in-cluded a detailed medical history, physical examination, blood and uri-nary studies, and renal and uriuri-nary tract ultrasound scans.
The prevalence of appendectomy in the history of the patients under study was compared with that of a control group of 270 subjects, 142 of whom were boys, aged 3 to 18.5 years (mean: 8.6 [SD: 3.9]). The control subjects were
consecutively observed for acute re-spiratory tract infection during a pe-riod of 2 years (2001–2003), and the previous history of appendectomy was speciﬁcally investigated by 1 of the au-thors (Dr Polito). We assumed that the prevalence of appendectomy in this group reﬂected the prevalence in the general population.
All children and parents were ques-tioned about the location and fre-quency of pain attacks. Evaluation dur-ing the ﬁrst visit was performed by 2 of the authors (Drs Polito and La Manna) on 43 and 57 different patients, respec-tively. Hence, we compared the re-ferred location of pain and the fre-quency of pain attacks recorded by the 2 independent observers in 2 different groups of subjects. The location of pain elicited on abdominal palpation by Drs Polito and La Manna was also com-pared. The frequency of attacks in our patients was compared with that re-ported in children with functional RAP
from our region14and from the United
States,15 and with
functional/psycho-somatic or organic gastrointestinal
RAP from Norway16and Sweden.17No
speciﬁc attempt was made to consis-tently quantitate the severity of pain. However, the pain was considered to be signiﬁcant if it caused the child to interrupt an ongoing activity to com-plain of pain or the child became inac-tive after verbalizing the symptom of pain.
Hypercalciuria was deﬁned as
calci-uria of⬎0.1 mmol (4 mg)/kg per day,
and hyperuricuria was deﬁned as uri-nary uric acid exceeding 815 mg/1.73
m2per day18on at least 2 of 3
noncon-secutive 24-hour urine collections made at home. The adequacy of urine collec-tions was checked by comparing the measured creatinine excretion with normal values. Hyperoxaluria was
de-ﬁned as oxalate excretion of⬎40 mg/
1.73 m2per day and hypocitraturia as
citrate excretion of⬍400 mg/g
creati-nine.18 Cystinuria was assessed with
the nitroprusside test in all patients and conﬁrmed by quantitative mea-surement in nitroprusside-positive
pa-tients. Hematuria was deﬁned asⱖ5
red blood cells per high-power ﬁeld in a centrifuged urine sample or
The2test, the2test for trend, and
the Wilcoxon rank test were used for
statistical analysis. APvalue of⬍.05
was considered signiﬁcant.
Figure 1 shows the enrollment and election of the patients included in the study. Table 1 lists the clinical charac-teristics of the study participants. The mean age was 9.8 (SD: 3.8) years. The mean duration of RAP before the ﬁrst visit was 12.5 months (SD: 11.4 [range:
3–50]). The mean duration of pain at-tacks was 127 minutes (SD: 105 [range: 10 – 600]). Nine patients had a urinary infection at the ﬁrst visit, and 2 had previous urinary infections. Serum electrolyte, calcium, phosphate, creat-inine, uric acid, bicarbonate, and para-thyroid hormone levels were normal in all patients.
There was no signiﬁcant difference in the referred central or lateral pain
lo-cation (P ⫽ .45 for both subjects
younger and older than 8 years of age) or in the frequency of pain attacks
(P⫽.79) recorded by Drs Polito and La
Manna. Pain on abdominal palpation was elicited by Drs Polito and La Manna in 27 and 18 subjects, respec-tively. There was no signiﬁcant differ-ence in the rates of central and lateral
pain elicited by the 2 observers (P⫽
.45 for both subjects younger and older than 8 years old).
A history of urolithiasis in at least 1 ﬁrst- or second-degree relative was present in 88 subjects. Two to 28 months (mean: 11.8) before the diag-nosis of urolithiasis, 37 patients un-derwent abdominal ultrasound exami-nation, the results of which were negative for urinary stones; however,
15 patients had microcalculi,19that is,
hyperechogenic spotsⱕ3 mm in
diam-eter in renal calyces, 5 patients had mild pyelectasis, and 2 patients had mild pyelectasis plus microcalculi. The ultrasound examinations were per-formed elsewhere in 25 cases and in our setting in 12. In the present analy-sis, we considered as the “ﬁrst visit” of
during the study period (n = 188)
Without RAP --- With RAP
(n = 78) (n = 110)
Hematuria/dysuria: 36 l
Acute/subacute pain l
+hematuria/dysuria: 26 l………Excluded
Acute-subacute pain: 12 l (n = 10)
Incidental discovery: 3 l Ureteropelvic obstruction: 3
Urinary infection: 1 l Vesicoureteric reflux: 1
l Renal cysts: 2
l Stipsis: 2
l Celiac disease: 1
Mental retardation: 1
l Elected (n = 100)
the latter 12 patients the time when stones were ﬁrst recorded.
A history of appendectomy was re-corded signiﬁcantly more often among the subjects with urolithiasis (16%;
P⬍.0001) than in the control group (4
of 270 [1.5%]). The 16 subjects with uri-nary calculi underwent appendectomy 1 to 48 months before our ﬁrst visit. In 9 of the 16 patients, dysuria and/or gross hematuria occurred 3 days to 18 months (mean: 9.5 months) after ap-pendectomy. In 2 of the 16 patients, mi-croscopic hematuria was recorded 1 and 20 months after appendectomy at our ﬁrst visit. One of the patients who underwent appendectomy also under-went a Meckel scan during another hospitalization. Four additional
pa-tients had previously been hospitalized for possible appendicitis. Another 9 patients had been hospitalized at least once for abdominal pain: 1 underwent a Meckel scan, 1 underwent gastros-copy, and 1 underwent contrast radi-ography of the upper digestive tract and gastroscopy. A total of 29 of our patients had been hospitalized at least once for abdominal symptoms.
Among the 35 patients younger than 8 years of age, the referred location of pain was lateral/ﬂank in 10 (29%),
cen-tral/diffuse in 24 (69%) and mainly hy-pogastric in 1. Among the 65 patients older than 8 years, the pain was later-al/ﬂank in 55 (85%), central/diffuse in 7 (11%), and mainly hypogastric in 3. A signiﬁcant decrease in the prevalence of central/diffuse location of pain with increasing age is apparent, with the most relevant decrease after 8 years (Fig 2). The mean frequency of pain at-tacks was 4 to 9 times lower than that reported in children with functional or organic gastrointestinal RAP (Table 2). Eighty-four patients had 4 or fewer days of pain per month.
0 50 100
3–8 8,1–13 13,1–18 Age groups, y
N. of cases (35) (45) (20)
Chi-square for trend p < 0.01
Lumbar/flank Mainly hypogastric
Prevalence of pain locations in 3 age groups.2for trend,P⬎.01.
TABLE 2 Mean (SD) Frequency of Pain Attacks in Children With RAP and Urolithiasis and in Four Studies of Functional or Organic Gastrointestinal RAP
Study Disorder (No. of Patients) Mean
Frequency, Mean (SD), d/mo
Present series, Campania, Italy Urolithiasis (100) 9.8 3.1 (4.0)a
Miele et al,14Campania, Italy Functional dyspepsia (26) 8.2 12.4 (11.1)
Irritable bowel syndrome (26) 5.0 15.6 (10.6)
Ball and Weydert,15Arizona Functional dyspepsia (14) 11.6 23.9
Irritable bowel syndrome (11) 11.6 18.1
Functional abdominal pain (14) 11.0 17.2
Størdal et al,16Norway Organic (20) and functional (24)
8.3 11.9 (8.5)
Alfvén,17Sweden Psychosomatic (48), possibly
psychosomatic (14), other etiologies (38)
aMedian: 1.5;ⱖ9 days/month in 9 subjects;ⱖ7 days/month in 12 patients; range: 0.5–20. bCalculated from the reported frequency of 4.6 attacks per week.
TABLE 1 Characteristics of 100 Children With RAP and Urolithiasis
Gross hematuria and/or dysuria⫹RAP 36
Upper tract 82b
Documented passage 11
Urinary excretion abnormality, mean of the abnormal values (range) Hypercalciuria, 5.5 (4.1–11) mg/kg
Hyperuricuria, 880 (844–1121) mg/1.73 m2per dc
Hypercalciuria, 6.3 (4.4–10) mg/kg per dc⫹Hyperuricuria, 946 (844–1086)
mg/1.73 m2per dc
Mild hyperoxaluria, 98 (64–130) mg/ 1.73 m2per d
Hypocitraturia, 177 (75–305) mg/g creatinine
No abnormality found 8
aAssociated with microcalculi in 57 patients. For imaging
documentation of stones, renal ultrasound was used for all patients, plain radiograph ﬁlm for 25 patients, and in-travenous urography for 11 patients.
bBilateral in 5 patients.
cTwenty-nine patients with hypercalciuria or/and
hyperuri-curia also had mild hyperoxaluria or/and hypocitraturia.
boys and girls (P⫽.60), between sub-jects younger and older than 8 years
(P ⫽ .24), or between subjects with
central/diffuse and lateral/ﬂank
loca-tion of abdominal pain (P⫽.25).
Hematuria and Dysuria
Fifty-three patients had no history of dysuria or gross hematuria, and only 35 had gross or microscopic hema-turia at the ﬁrst visit. Forty-one pa-tients had no history of hematuria or dysuria and normal urinalysis results at the ﬁrst visit. Of the 47 patients with a history of gross hematuria or dys-uria, 22 (47%) had no dysuria and nor-mal urinalysis results at the ﬁrst visit. Central/diffuse location of abdominal pain, with no history of dysuria and he-maturia and normal urinalysis results at our visit were recorded in 16 of our patients and in 12 of 35 (34%) of those aged 8 years or younger.
Of the 45 subjects with pain on palpa-tion of the abdomen, as many as 32 (71%) had neither hematuria nor dysuria at the time of the visit. Of the 37 patients who had negative ultra-sound results before the ﬁrst diag-nosis of calculi, 21 (57%) had no his-tory of dysuria or hematuria and underwent additional follow-up in-vestigations only because of a family history of nephrolithiasis.
Because of the lack of population-based studies, we do not know how many children with RAP have urolithia-sis. Moreover, authors of studies on children with urolithiasis have re-ported the rate of those presenting with abdominal/ﬂank pain with no speci-ﬁcation of the proportion of acute/ subacute and chronic-recurrent
ab-dominal pain.1–5The lack of emergency
service in our department likely en-hanced the proportion of those with recurrent pain in respect to those
representative of the universe of chil-dren with urolithiasis.
This study shows a low frequency of pain attacks in children with urolithia-sis, which has not yet been reported in the literature. The mean frequency of pain attacks was 4 to 9 times lower in our patients than in children with func-tional or organic gastrointestinal RAP from our own and other countries. In contrast, the maximum difference in the frequency of attacks among the various kinds of functional or organic gastrointestinal RAP was less than twofold (Table 2). Hence, the low fre-quency of pain attacks clearly distin-guishes the population of children with urolithiasis from those with functional or organic gastrointestinal RAP. We cannot establish deﬁnite cutoff values. In our series, however, the mean fre-quency of pain attacks was 3.1 days/ month, whereas the median was 1.5 days/month (Table 2). A frequency of pain attacks of 4 days/month or less may empirically suggest urolithiasis, which has even been indicated as an
index of healing of functional RAP,15
whereas this frequency was recorded in as many as 84% of our patients. RAP occurs in up to 19% of all children and adolescents, with a median
preva-lence of 8.4%,8 and is most often
functional.6,9,16,17Therefore, it is likely
that the remaining 16% of our pa-tients with more frequent pain at-tacks included a number of subjects with functional RAP incidentally as-sociated with urolithiasis.
Gross or microscopic hematuria and dysuria are the main “red-ﬂag” symp-toms reported for involvement of the
urinary tract in children with RAP.6,8
Nevertheless, these symptoms oc-curred inconstantly in our patients. In fact, half of our patients had no history of dysuria or hematuria, and more than one third had no history of
dys-latter were investigated for urolithia-sis because of RAP associated with a family history of urinary calculi, which accounts for a high risk of kidney
stones.20,21Actually, more than half of
our patients who had a negative ultra-sound scan result before the ﬁrst diag-nosis of urolithiasis had no history of dysuria or hematuria and underwent additional follow-up investigations be-cause of a family history of kidney stones. Moreover, approximately half of our patients with a history of hema-turia or dysuria did not have these symptoms at the ﬁrst visit. Finally, he-maturia and dysuria did not necessar-ily correlate with pain; as many as 71% of our patients with pain elicited by ab-dominal palpation had neither hema-turia nor dysuria at the time of the visit. Pain attacks, as well as hematuria and dysuria, likely result from the mobiliza-tion and passage of calculi or crystals. Hence, it is not surprising that the occurrence of these symptoms was largely intermittent or sporadic. Al-though no study has speciﬁcally ad-dressed children with RAP and uroli-thiasis, the inconstant occurrence of hematuria and dysuria has been re-ported in many series of children with
kidney stones.1–5,7It is worth keeping
this fact in mind, because the lack of occurrence of hematuria and dysuria in clinical practice may erroneously lead to exclusion of the urinary tract as a possible cause of pain. The drawback is that even in most scientiﬁc reports on RAP, the urologic origin of pain was excluded only on the basis of “normal urinalysis and/or urine
cul-ture or of the lack ofovert
genitouri-nary problems”10; similar guidelines
were established by the Rome III Committee for Functional
younger than 8 years in our study, and ﬂank pain was the rule in patients older than 8 years (Fig 2). This could reﬂect the development of sensory dis-crimination during childhood and is in keeping with the acquisition of body
outline around the age of 8.23We
previ-ously found similar results in children with hypercalciuria and/or hyperuri-cosuria, most of whom, however, had
no urinary stones.11When abdominal
pain is central/diffuse and is not asso-ciated with dysuria and hematuria, as in 34% of our patients aged under 8 years, it might well mimic functional RAP. Imaging studies performed immedi-ately after pain attacks may fail to re-veal urinary calculi, because the stones could have been passed shortly before the evaluation. In fact, 2 to 28 months before the diagnosis of uroli-thiasis, 37% of our patients underwent abdominal ultrasound scanning that did not show urinary calculi. This is in
keeping with reports that ⬎10% of
children with hypercalciuria and/or hyperuricosuria and no demonstrable stones on ﬁrst evaluation may form
calculi within 1 to 4 years.19,24–26
Actu-ally, in 15 of our 37 patients, ultra-sound showed microcalculi that could be considered the ﬁrst step in stone
formation.19,24 The ﬁnding of
microcal-culi, however, depends on interobserver and intraobserver variability and skills, and microcalculi are not generally
rec-ognized.27,28 The possibility of a
false-negative ultrasound scan or plain ra-diograph ﬁlm in a subject with bowel distension caused by recent colic should also be taken into account. Low-dose unenhanced computed tomogra-phy is more accurate than ultrasonog-raphy in detecting calculi and has been recommended for all children with per-sistent urolithiasis symptoms and
nondi-agnostic ultrasound scans.28Compared
with ultrasound, however, computed to-mography involves higher costs and ra-diation, which are signiﬁcant issues in children with possible urolithiasis be-cause of the frequent recurrence of this condition.
The inconstant occurrence of hematuria and dysuria, the central/diffuse location of abdominal pain in most young chil-dren, and the lack of calculi shown on imaging studies performed after an epi-sode of pain may result in failure to iden-tify the urologic origin of pain. This could explain, for the most part, the high rates of previous inconclusive hospitalizations for abdominal pain (29%) and appendec-tomy in the present series. Actually, the prevalence of appendectomy in our con-trol group (1.5%) is comparable to that estimated from a large survey in the
United States29and is signiﬁcantly (P⬍
.0001) lower than the rate (16%) for our patients.
Searching for urolithiasis in children with RAP may be difﬁcult and expen-sive. In fact, a negative imaging study result after a pain attack does not ex-clude the previous and/or subsequent occurrence of urinary stones and may need to be repeated later. This is par-ticularly important in the presence of a urinary solute excretion abnormality such as hypercalciuria or hypocitra-turia, which, in turn, may require
re-peated30and costly31evaluations to be
ascertained. Moreover, despite an up-ward trend in incidence, overt pediat-ric urolithiasis remains infrequent in
Western countries,5,28whereas RAP is
frequent. It seems advisable to per-form at least 2 renal ultrasound exam-inations 1 to 2 years apart and 3 non-consecutive complete evaluations of urinary solute excretion abnormalities in outpatient children with RAP and a family history of urolithiasis, even in the absence of speciﬁc urinary signs and symptoms, and in younger pa-tients, although the pain may be cen-tral or diffuse in the whole abdomen. Computed tomography may be partic-ularly useful in the emergency depart-ment after a nondiagnostic ultrasound scan. Restricting these investigations to patients with infrequent painful ep-isodes (4 days/month or less) will help improve the cost/beneﬁt ratio of this approach.
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DOI: 10.1542/peds.2009-0825 originally published online November 9, 2009;
Cesare Polito, Angela La Manna, Giuseppe Signoriello and Antonio Marte
Recurrent Abdominal Pain in Childhood Urolithiasis
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