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PEDIATRICS Vol. 107 No. 1 January 2001, pp. 86-90
From the Department of Pediatrics, Second University of Naples, Naples, Italy.
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ABSTRACT |
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Top
Abstract
Results
Discussion
Conclusion
References
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Objective. Idiopathic hyperuricosuria (HU) was previously reported in only a limited number of children with hematuria. We aimed to outline the clinical presentation and natural history of HU not only in children with hematuria, but also in those with dysuria and/or recurrent abdominal/flank pain and a family history of urolithiasis.
Study Design. Retrospective analysis of data at diagnosis
from 102 consecutive children with HU and outcome analysis of 26 of
them who were followed 
1 years (mean: 3.1) with no specific
therapy.
Results. Sixty-one participants had HU and 41 had HU + hypercalciuria. Fifty-two patients had no hematuria among the presenting symptoms, more than one third had normal urinalysis at our first examination, one half had microcalculi (<3 mm in diameter) at renal sonography, and 12% had stones (4-18 mm). Thirty participants of the 39 with no hematuria at our first examination (77%) showed microcalculi or calculi at renal sonography. The patients with microcalculi were significantly older than were those without microcalculi. During the follow-up, 4 of 26 children never had hematuria and 8 had no hematuria during most of the follow-up period. Two patients who had a calculus at first visit and 3 who formed calculi 4 to 12 mm in diameter, after 1 to 3.5 years subsequently passed them in the urine.
Conclusions. The lack of hematuria is not predictive of absence of urolithiasis. Therefore, it may be misleading to judge on the efficacy of a given therapy only based on disappearance of hematuria. HU and hypercalciuria have to be suspected in children with dysuria and those with recurrent abdominal/flank pain and familial history of urolithiasis, although they have no hematuria. Key words: hyperuricosuria, hypercalciuria, urolithiasis, hematuria, dysuria, abdominal pain.
Hyperuricosuria (HU) is frequently associated with adult
urolithiasis.1,2 Although idiopathic hypercalciuria (HC)
has been extensively investigated as a cause of hematuria and
urolithiasis in children,3-6 childhood idiopathic HU has
received little attention. Two previous studies reported
57 and 308 children with HU who were examined
for hematuria and who were followed between 6 and 36 months. Treatment
with purine-restricted diet, allopurinol, or potassium citrate was
accompanied by normalization of uricosuria and disappearance of
hematuria.7,8 Microhematuria and HU persisted in untreated
patients.7,8 None of the patients in both studies had
calculi at first diagnosis of HU. Kidney stone formation during
follow-up was detected in only one of these studies in which 13% of
untreated patients had stones at 6 months and 6% at 12 months, but
none of the untreated children had stones after the first
year.8 Also in adults, HU is usually reported at
investigation of patients with hematuria.9,10 In 6/11
adults with HU who received allopurinol and in 10/17 with HU + HC who
received allopurinol and thiazides, hematuria resolved completely as
soon as calciuria and uricosuria became normal.9 Gross
hematuria resolved after normalization of calciuria and uricosuria
under allopurinol and indapamide in an adult patient.10
It is our current practice to investigate for HU and HC not only in
children with hematuria, but also in those presenting with symptoms
suggestive of cristalluria (dysuria and/or recurrent abdominal or flank
pain in participants with familial history of urolithiasis). In the
present retrospective study, we report on data at first diagnosis of
102 children with HU and on the outcome of 26 of them who had a
long-term follow-up with no specific therapy.
We reviewed the records of children with HU and normal serum
uric acid and creatinine concentration, observed between January 1992 and June 1999. Most of them attended our clinic as outpatients. The
patients with generalized defect of tubular solute reabsorption were
excluded from this study. One hundred and two children, 48 boys and 54 girls, aged 6.4 ± (standard error of the mean) .3 years (range:
2.1-12.8 years) were selected for the analysis of clinical
presentation. For the study of natural history, we selected 26 patients
who were followed for 1 year at least and from whom at least 1 yearly
urinary and renal sonographic investigation was available and who did
not receive any dietary or specific drug prescription, apart from the
recommendation of high fluid intake. Five children with HU + HC who
received diuretics during the study were excluded from the outcome
analysis.
HU was defined by urine uric acid concentration corrected for
creatinine clearance (U/Cr = urine uric acid [mg/dL] × plasma creatinine [mg/dL]: urine creatinine [mg/dL]) of >.53 mg/dL of glomerular filtration rate (GFR).11 HC was defined by a
calciuria >4 mg/kg/24 hours. At initial workup, 3 nonconsecutive
24-hour urinary collections were considered to minimize the daily
variations, and the highest values were taken for diagnosis of HU and
HC. At follow-up determinations, only one 24-hour urine collection was
taken. On occasion of each determination of calciuria and uricosuria on
the 24-hour urine collection, a urinalysis on a freshly voided urine
sample was also performed.
Renal ultrasound examination was always performed by the same operator
by a Toshiba Sonolayer SSA 250 (Toshiba Italia, Milano) with a
sound convex of 3.75 MHz equipped with a high-resolution zoom. Calyceal
microlithiasis was defined by the finding of hyperechogenic spots in
renal calyces. These microcalculi were usually devoid of shade cone and
were less than 3 mm in diameter.12 The hyperechogenic
spots were recorded as microcalculi only when they were found on
different scans obtained in different orthogonal plans. In a previous
study, when assessing the reproducibility of the sonographic diagnosis
of calyceal microlithiasis, we found concordance between 2 independent
observers in 92% of participants examined, with a Of 102 children, 77 (75%) had at least one first- or
second-degree relative with a history of urolithiasis.
Sixty-one children, 23 boys and 38 girls 6.8 ± .4 years of age
had HU (mean U/Cr: .71 ± .02 mg/dL/GFR; range: .54-1.32).
Forty-one children, 25 boys and 16 girls 5.8 ± .3 years of age
had HU (mean U/Cr: .74 ± .02 mg/dL/GFR; range: .56-1.2) and HC
(mean calciuria: 6.6 ± .4 mg/kg/24 hours; range: 4.1-14.4). No
significant difference in U/Cr was found between HU and HU + HC
patients (P = .46). In the HU + HC group, U/Cr and
calciuria values were not correlated (P = .14).
Presenting Symptoms
The presenting symptoms in the 102 children studied occurred alone
or in combination (Tables 1 and
2) between 3 days and 44 months (mean:
16 months) before our first visit. The most frequent of the isolated
presenting symptoms were microscopic hematuria found at routine
urinalysis in 26 patients and abdominal and/or flank pain in 25 different patients. Seven children had passed gravel into urine 3 to 24 days before our first visit. Fifty-two patients had no hematuria among
the presenting symptoms. The prevalence of each presenting symptom
among the children with HU and those with HU + HC were no different
with the exception of microscopic hematuria that was significantly more
frequent in HU participants (Table 2).
TABLE 1 TABLE 2
PATIENTS AND METHODS
value of .83 indicating good agreement.12 Urinalysis, urineculture,
assessment of 24-hour urinary calcium, uric acid, citrate, and
creatinine excretion were performed in all patients. Qualitative
measurements of urinary cystine were performed by the nitroprusside
test to exclude cystinuria. Hematuria was defined as 5 or more red
blood cells per high-power field in a centrifuged urine sample on at
least 2 different days. Phase contrast microscopy of urinary red blood
cells was conducted on urine samples to assess whether they were of
glomerular or nonglomerular origin.13 Serum calcium, uric
acid, phosphates, creatinine, and bicarbonate were measured. Calcium
was measured by the o-cresolphtalein complexone method and
uric acid by enzymatic colorimetric test. Urinary oxalate, magnesium,
and phosphorus were not measured. Hypocitraturia was considered as the
excretion of <300 mg of citrate per gram of creatinine in girls and
<125 mg in boys.14 The t test for unpaired
data, 
2, Fisher's, and Spearman rank
correlation tests were used for statistical analysis. A P
value <.05 was considered significant.
RESULTS
Top
Abstract
Results
Discussion
Conclusion
References
Presenting Symptoms in 102 Patients With
HU
Whole Occurrence of the Main Presenting Symptoms in 102 Patients With
HU
Data at Diagnosis
All patients had normal blood pressure and normal serum uric acid,
calcium, phosphates, and bicarbonate, and none of them had proteinuria.
More than one third of the patients had normal urinalysis (Table
3). Microscopic hematuria of
nonglomerular origin was found in three fourths of HU participants and
in less than one half of those with HU + HC (P = .001).
Nearly one half of the patients had normal renal sonography, one half
had microcalculi, and 12% had calculi 3 mm (Table 3).
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None of the 7 children having passed gravel had microscopic hematuria and 2 of them had normal renal sonography. Thirty participants (77%) of the 39 with normal urinalysis had microcalculi or calculi (7 patients) at renal sonography.
Overall, 32 participants (12 HU and 20 HU + HC) never had hematuria, before or at our first workup: 24 of them (75%) had microcalculi or calculi (6 patients). Renal sonographic findings of HU and HU + HC patients were coarsely similar (Table 3).
In the HU + HC group, the participants with stones were significantly older than were those without stones (Table 4). The patients with microcalculi were older than were those without microcalculi, both in the HU and in HU + HC groups, but the difference in age did not reach significance (Table 4). Considering HU and HU + HC groups together, the children with microcalculi were 7.1 ± .5 years of age and those without microcalculi were 5.4 ± .4 years of age (P = .011).
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Follow-Up Data
Twenty-six children who did not receive specific therapy or operative stone removal were followed 1 to 6.8 years (mean: 3.1 years; Fig 1). Fifteen of them had HU and 11 had HU + HC.
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Eighty-four evaluations of uricosuria on a single 24-hour urine collection were performed after the initial assessment in the 26 patients. Twenty-three of those determinations in 14 participants (27%; 6 with isolated HU: numbers 1, 2, 4, 7, 11, 13, and 8 with HU + HC: numbers 16-18, 20, 22-24, and 26; Fig 1) gave values of U/Cr <.53 mg/dL/GFR. Only one patient had both normal urinalysis and renal sonography on that occasion, while the others had microcalculi or hematuria or both. On occasion of the finding of U/Cr <.53 mg/dL/GFR, 4 of the children with isolated HU had normal sonography and microscopic hematuria (numbers 1, 2, 4, and 11), one had microcalculi and microscopic hematuria (7), and one had microcalculi and normal urinalysis (13). Five of the 11 patients with HU + HC (numbers 16-18, 21, and 24) had calciuria <4 mg/kg/24 hours in one fourth to one seventh of the determinations during the follow-up, while the others had always values >4.
Four patients (numbers 5, 19, 21, and 25) never had hematuria, while 8 (numbers 6-8, 15, 18, 20, 24, and 26) had no hematuria during >60% of their follow-up (Fig 1).
Five patients had microcalculi in all, and 5 patients in none of the
sonographies during the follow-up. In 15 patients, the microcalculi
that were present at one sonography were not found at subsequent
examination and vice versa (Fig 1). Two patients (numbers 6 and 25) had
a calculus (5 and 7 mm) at first examination and normal sonography and
urinalysis at next evaluation. Patients 8, 11, and 26
ie, 2/15 (13%)
of the HU and 1/11 (9%) of the HU + HC participantsshowed a calculus
(4 to 12 mm) after 1 to 3.5 years follow-up. At the next evaluation,
they had normal urinalysis and sonography (number 8), microcalculi and
microscopic hematuria (number 11), and microcalculi and normal
urinalysis (number 26).
At last visit, 11/26 patients (numbers 5, 6, 8, 10, 18-21, and 24-26) had normal urinalysis, with 6 of them showing microcalculi, while the others had microscopic hematuria with 10 of them showing microcalculi (Fig 1).
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DISCUSSION |
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Top
Abstract
Results
Discussion
Conclusion
References
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The main findings of the present study are: 1) the presence of microcalculi in approximately one half of children with HU, 2) the lack of hematuria among presenting symptoms in more than one half of them, and 3) the lack of correlation between the presence of hematuria and that of microcalculi or calculi.
In contrast with previous reports,7,8 we have taken into account the sonographic finding of hyperechogenic spots <3 mm in diameter in renal calyces and we have considered them as microcalculi.12,15 Microlithiasis and the related crystalluria have been indicated as possible explanation of some hematurias.16 Also, minute stones have been found at renal sonography in 27% of children with idiopathic HC.17 In the present study, more than one half of the patients had microcalculi at diagnosis and only 4/26 (15%) never showed microcalculi at follow-up sonographies. Yet, microcalculi as well as calculi 4 to 12 mm in diameter were passed in the urine even in the absence of specific therapy (Fig 1). However, the risk of forming microcalculi seems to increase with age.
All the children with HU reported in previous studies7,8 had hematuria. Actually, those patients were investigated for HU just because they suffered from hematuria. In contrast, our series included also patients with other presenting symptoms, such as dysuria or abdominal pain. More than one half of our patients had no hematuria among presenting symptoms, more than one third had no hematuria at our first examination, and nearly one half had no hematuria during all or most of follow-up. These findings indicate that HU has to be suspected in cases of symptoms suggestive of cristalluria (dysuria and/or recurrent abdominal/flank pain in participants with familial history of urolithiasis) even in the absence of hematuria.
We found that a normal urinalysis is not predictive of normal sonography. In fact, microcalculi or calculi were present in 77% of patients with normal urinalysis at our first examination and in 75% of those who did not have hematuria before or at our first examination. Also, during the follow-up, the normal urinalysis was not associated with normal sonography and vice versa (Fig 1). The lack of hematuria or its disappearance is not in contrast with the persistence/accretion of microcalculi or calculi. In fact, considering that hematuria as well as the other symptoms and signs likely depend on the emission of calculi or microcalculi or their fragments, it is not surprising to not find (micro)calculi at sonography after those symptoms. The lack of correlation between the presence of hematuria and the presence of (micro)calculi indicates that it may be misleading to judge on the efficacy of a given therapy only based on the disappearance of hematuria.
In 27% of the single 24-hour determinations during follow-up, we found normal uricosuria, which, however, was nearly always associated with hematuria, microlithiasis, or both. This indicates that repeated measurements are needed in follow-up studies before concluding that a given therapy can normalize uric acid excretion. Similarly, in some of our patients with HU + HC we did not find HC in all of the measurements during the follow-up. Dietary data are not available in our patients. However, differences in dietary intake may account for some differences in findings of HU and HC in repeated determinations. Actually, it is known that excessive protein and sodium intake may contribute to the high level of urinary uric acid and calcium excretion.1,18,19 The concomitance of HC in patients with HU was associated with significantly less frequent microscopic hematuria but with no different prevalence of the other clinical or sonographic signs (Tables 2 and 3).
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CONCLUSION |
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Top
Abstract
Results
Discussion
Conclusion
References
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HU, microcalculi, and stones may be present even in children without hematuria. HU and HC have to be suspected in children with symptoms suggestive of cristalluria (dysuria and/or abdominal and/or flank pain in participants with familial history of urolithiasis), although they have no hematuria.
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FOOTNOTES |
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Received for publication Aug 3, 1999; accepted Apr 14, 2000.
Reprint requests to (A.L.M.) Dipartimento di Pediatria, Via S. Andrea delle Dame 4, I-80138, Napoli, Italy. E-mail: bruno.nobili{at}unina2.it
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ABBREVIATIONS |
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HU, hyperuricosuria; HC, hypercalciuria; GFR, glomerular filtration rate.
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REFERENCES |
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Abstract
Results
Discussion
Conclusion
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This article has been cited by other articles:
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  R. S. Gillespie and F. B. Stapleton Nephrolithiasis in Children Pediatr. Rev., April 1, 2004; 25(4): 131 - 139. [Full Text] [PDF]
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