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|Year : 2010 | Volume : 21 | Issue : 4 | Page : 673-677 |
|Hypercalciuria in children with urinary tract symptoms |
MK Fallahzadeh1, MH Fallahzadeh1, A Mowla2, A Derakhshan1
1 Nephro-urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Internal Medicine, Brookdale Hospital and Medical Center, State University of New York (downstate), New York, USA
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|Date of Web Publication ||26-Jun-2010 |
| Abstract || || |
We performed this prospective study to determine the urinary calcium to creatinine ratio (Ca/Cr) in children with different urinary symptoms. We studied 523 children in our nephrology clinic with an age range of 3 to 14 years (mean= 8) and male to female ratio of 0.61. All the children had at least one of the urinary tract symptoms (dysuria, frequency, urgency, abdominal and/or flank pain, diurnal incontinence or enuresis), microscopic hematuria, urinary tract infection or urolithiasis. Fasting urine was collected for measuring calcium and creatinine and the results were compared to the values for the normal Iranian children. Ca/Cr ratio of more than 0.2 (mg/mg) was considered as hypercalciuria. Of all the patients, 166 (31.3%) were hypercalciuric. Urine Ca/Cr ratio was significantly higher in all the subgroups with one or more of the urinary symptoms (P< 0.001). We conclude that urine Ca/Cr ratio is significantly increased in children with all types of urinary symptoms. We recommend measuring urinary calcium in all children with urinary tract symptoms, especially if unexplained.
|How to cite this article: |
Fallahzadeh M K, Fallahzadeh M H, Mowla A, Derakhshan A. Hypercalciuria in children with urinary tract symptoms. Saudi J Kidney Dis Transpl 2010;21:673-7
|How to cite this URL: |
Fallahzadeh M K, Fallahzadeh M H, Mowla A, Derakhshan A. Hypercalciuria in children with urinary tract symptoms. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2014 Mar 3];21:673-7. Available from: http://www.sjkdt.org/text.asp?2010/21/4/673/64641
| Introduction || || |
A variety of etiologies have been proposed for different urinary symptoms or paraclinical findings, including viral, chemical, physical and metabolic causes.  Hypercalciuria may be an underlying cause of different urinary tract symptoms in clinical practice, including urinary frequency, urgency and/or dysuria, often associated with gross or microscopic hematuria.  In children, noncalculous manifestations of hypercalciuria are reportedly more common than urolithiasis. ,
In this study, we measured urinary calcium to creatinine (Ca/Cr) ratio of the patients visited in our nephrology clinic with different urinary symptoms to determine prevalence of hypercalciuria.
| Subjects and Methods || || |
We evaluated 529 consecutive children referred to our center from March 2003 to September 2004 with various urinary complaints including dysuria, frequency, diurnal incontinence, nocturnal enuresis, urgency, abdominal and/or flank pain, microscopic hematuria, urolithiasis, and urinary tract infection (UTI). Patients with gross hematuria and/or gross proteinuria were not included in this study.
Our center is a referral center for children with different ethnic and socio-economic status from different parts of Iran. A thorough medical history with specific emphasis on voiding patterns and physical examination besides urinalysis and urine culture were done. In 523 patients, fasting urine sample was evaluated for calcium and creatinine concentrations. Urinary calcium levels was determined by the cresolphthalein complexone spectrophotometric method and creatinine was measured with the Jaffe's reaction. , All the tests were performed in one laboratory.
Six patients refused to continue participation in the study. The remaining patients were divided into different groups according to their symptoms or findings including microscopic hematuria, urolithiasis or UTI. Microscopic hematuria was defined as five or more red blood cells per high-power field on microscopic examination in at least two different urine samples. UTI was defined as two urine cultures with more than 100000 colonies of one type of pathogen. Some patients with combined symptoms or the urinary findings were included in more than one group.
In each study subgroup, the frequency of hypercalciuria was calculated. Urine Ca/Cr ratio greater than 0.2 mg/mg was considered as hypercalciuria. In each group the mentioned variables were compared to normal reference values in Iran. Normal reference values for urinary Ca/Cr ratio in healthy Iranian children were reported by Safarinejad.  Among different age groups studied by Safarinejad, those matched with the age groups in our study (3-14 years) were selected for comparison. Urine Ca/ Cr ratio was measured using the same method in both studies.
| Statistical Analysis || || |
For statistical analysis, the t-test was used to compare the mean values of patients and normal individuals and chi-square test was used to compare the frequency of hypercalciuria in patients and normal individuals. P< 0.05 was considered as statistically significant.
| Results || || |
The study group comprised of 523 patients, including 206 males (39.4%) and 317 female (60.6%) with a mean age of 8.16 ± 3.25 (range: 3-14 years). Past medical history of renal diseases was positive in 133 (25.4%) patients and family history of renal and/or urinary tract disorders in 204 (39%). Of all the patients, 166 (31.3%) were hypercalciuric.
The mean urinary Ca/Cr ratio was significantly higher in the symptomatic patients than normal individuals (0.04 ± 0.05) with P< 0.001. A statistically significant difference was observed between the mean urinary Ca/Cr ratio of individuals with age of 3 to 7 years and older children (P= 0.003). However, the mean urinary Ca/Cr ratio was not significantly different between male and female patients (P> 0.05).
The number of the patients with hypercalciuria in each subgroup is shown in [Table 1]. Frequency of hypercalciuria in different subgroups were significantly higher than the frequency of hypercalciuria in healthy Iranian children (P< 0.0001) and also normal individuals from most other nations. ,,,
| Discussion || || |
Our results confirm previous observations regarding the association of hypercalciuria with the different urinary tract symptoms. Previous reports have shown that unlike adults with hypercalciuria, in whom urolithiasis is the most common manifestation, children with hypercalciuria have been reported to present with predominantly noncalculous lower urinary tract symptoms. These symptoms and findings include microscopic and gross hematuria, frequency, urgency, dysuria, enuresis, urinary tract infection, urinary incontinence and suprapubic pain. ,,,,, While previous studies initially identified children with hypercalciuria and then traced the common symptoms, ,, we initially identified a subset of urinary symptoms and findings and then determined the incidence of hypercalciuria. We relied on spot urine Ca/Cr ratio in order to diagnose hypercalciuria; several other studies support spot urine evaluation as an accurate marker for hypercalciuria with specificity and sensitivity of more than 90%. ,,,, In our study and other reports that use fasting (first or second) urine for measurement of calcium, absorptive hypercalciuria and hence the rate of hypercalciuria may be overlooked.
Recent studies have demonstrated that the urinary Ca/Cr ratio varies with age and geographic area. ,,, Our patients were compared to healthy Iranian children,  which in our belief is a valid comparison.
As shown in [Table 1], a significant number of patients with urinary symptoms had elevated urinary Ca/Cr ratio. The incidence of hypercalciuria in the patients with dysuria and day-time frequency were 32.2% and 32.6% respectively, while in a similar study by Parekh et al,  the incidence of hypercalciuria was 22% in patients with pure dysuria, 21% in those with pure childhood daytime frequency, and 28% in individuals with frequency, urgency and dysuria simultaneously. Due to statistical limitations, we could not determine the incidence of hypercalciuria in patients with combined symptoms.
Vachvanichsanong et al  demonstrated that hypercalciuria is frequently associated with urinary incontinence in children. Of 124 children who were evaluated for hypercalciuria, 23% had urinary incontinence. They concluded that random urinary Ca/Cr ratio, which was used to screen hypercalciuria, should be part of the initial evaluation for urinary incontinence in children. In our study, 39.6% of patients with urinary incontinence were hypercalciuric, which was significantly higher than normal individuals (P< 0.0001). These findings are comparable to that of Vachvanichsanong et al. 
The incidence of hypercalciuria was 30.3% in the patients with nocturnal enuresis, while in normal asymptomatic children is in the range of 2.9% to 9.2%. , Aceto et al,  indicated that hypercalciuria has a pivotal role in nocturnal enuresis. They illustrated that high level of overnight calciuria was significantly associated with low nocturnal ADH and polyuria during sleep. They concluded that calciuria should be evaluated in the diagnostic approach to nocturnal enuresis. Furthermore, a patient was reported with diagnosis of diabetes insipidus secondary to idiopathic hypercalciuria presenting with nocturnal enuresis. 
In our study, 26.5% of patients with abdominal and/or flank pain had hypercalciuria. The authors of a similar study recommended that hypercalciuria should be considered in the differential diagnosis of recurrent abdominal or flank pain in children. 
Microscopic hematuria has been reported to be the most common noncalculous manifestation of hypercalciuria in children in previous studies. ,, Five children were evaluated for painless hematuria by Roy et al  and they inferred that hypercalciuria was the probable cause of the unexplained painless hematuria in those children. Hypercalciuria was also found in about 30% of patients who presented with hematuria in other studies. ,, In our study, 32.9% of the patients with microscopic hemauria had hypercalciuria.
Although noncalculous manifestations in children with hypercalciuria are reportedly more common than urolithasis, , a large number of patients (38.6%) with urolithiasis had hypercalciuria in our study. Hypercalciuria is regarded as one of the major etiological factors in the development of calcium containing renal stones. ,,
Recurrent urinary tract infection (UTI) is not widely considered as a clinical manifestation of hypercalciuria in children. Heliczer et al  reported recurrent UTI in a review of noncalculi urinary tract disorders in children with hypercalciuria. Lopez et al  also indicated that hypercalciuria may play a predisposing role for recurrent UTI in children by promoting the formation of microcrystals, which damage the uroepithelium. As shown in [Table 1], in our study 30.1% of patients with UTI had hypercalciuria.
Hypercalciuria in different groups of children in this study was significantly higher than normal age-matched individuals. Our results are in concordance with the results of the study done by Tekin et al  in Turkey. They compared the mean urinary Ca/Cr ratio of the patients including those with hematuria, enuresis, frequency, and abdominal pain with the control group and showed significant differences. A similar study in Venezuelan children with UTI also showed significant difference between the mean urinary Ca/Cr ratio of the patients and normal individuals.  In some patients with urinary symptoms, hypercalciuria may be an incidental finding and not the cause of the symptoms. The urinary Ca/Cr ratio in our study was independent of gender but dependent upon age. Studies by Safarainejad  (non-fasting urine), Akashi et al  and Tekin et al  were all in favor of our results about gender and age differences.
In conclusion, hypercalciuria is common in children with different symptoms related to the kidneys and urinary tract. We recommend measuring urine calcium in patients with different urinary symptoms, particularly if unexplainable.
| Acknowledgement || || |
Financial support was provided by a grant from vice chancellor for research in Shiraz University of Medical Sciences, so it is appreciated.
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M H Fallahzadeh
Shiraz Nephro-urology Research Center, Faghihi Hospital, Shiraz
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