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ORIGINAL ARTICLE
Year : 2009  |  Volume : 1  |  Issue : 2  |  Page : 52-55 Table of Contents     

Hypercalciuria, a promoting factor to urinary tract infection in children


1 Department of Pediatric Nephrology, St Al-Zahra Hospital, Isfahan University of Medical Sciences, Iran
2 Department of Endocrine and Metabolism, Amirkola Children Hospital, Babol Medical University, Iran

Date of Submission31-Jan-2009
Date of Acceptance22-Jun-2009
Date of Web Publication26-Sep-2009

Correspondence Address:
Alaleh Gheissari
Department of Pediatric Nephrology, St Al-Zahra Hospital, Isfahan University of Medical Sciences
Iran
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DOI: 10.4103/0974-7796.56046

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   Abstract 

Aim: Urinary tract infection (UTI) is one of the most common diseases of urogenital tract in children. Detecting predisposing factors for UTI takes an important place in managing patients with UTI. Recently, a few studies emphasized on idiopathic hypercalciuria (IH) as a predisposing factor for UTI and dysfunctional voiding. Therefore, we carried out a survey to find out whether non-calculus IH is a contributing factor in children with the first attack of pyelonephritis.
Materials and Methods: This is a case-control study carried out on 60 children aged 2-11 years admitted at St Al-Zahra hospital, Isfahan, Iran, with the first episode of upper UTI and 200 age- and gender-matched normal healthy children between September 2003 and February 2005. We used second fasting spot urine sample to measure calcium and creatinine. Two urine samples were obtained one week apart to increase the accuracy of measurement. All samples were collected after at least 6 weeks of completing the treatment course of pyelonephritis. Ultrasound examination and VCUG were performed in all patients before entering the survey as case group to rule out obstruction and VUR.
Results: Mean age of case and control group were 4.86 ± 3.08 years and 4.22 ± 2.9 years, respectively. The mean calcium to creatinine ratio (Ca/Cr) in case and control group were 0.308 ± 0.21 and 0.208 ± 0.12 mg/mg, respectively, P < 0.001. The difference between the mean values of these two groups was significant only in age group ≤6 years, P < 0.0001 and odds ratio was 2.1 (95% CI 1.03-7.8). After determining the mean values of urine Ca/Cr ration according to both age groups and gender, it was cleared that only significant difference was related to male <6 years.
Conclusion: The likelihood of hypercalciuria should be assessed especially in male children with UTI and without any urinary tract obstruction.

Keywords: Children, idiopathic hypercalciuria, urinary tract infection


How to cite this article:
Gheissari A, Adjoodani T, Eshraghi P. Hypercalciuria, a promoting factor to urinary tract infection in children. Urol Ann 2009;1:52-5

How to cite this URL:
Gheissari A, Adjoodani T, Eshraghi P. Hypercalciuria, a promoting factor to urinary tract infection in children. Urol Ann [serial online] 2009 [cited 2019 Sep 21];1:52-5. Available from: http://www.urologyannals.com/text.asp?2009/1/2/52/56046

[±±±TAG:2]Introduction[/TAG:2]

Urinary tract infection (UTI) is one of the most common diseases of urogenital tract in children. About 3-5% of girls and 1% of boys experience at least one episode of UTI during childhood. [1] Kidney scar due to UTI is an etiology for developing hypertension and various degrees of renal functional impairment. Therefore, detecting predisposing factors for UTI takes an important place in managing patients with UTI. Vesicoureteral reflux (VUR), voiding dysfunction, urinary tract obstruction (UTO), poor hygiene and anatomical abnormalities are some of the known predisposing factors for developing UTI. However, a substantial number of these patients develop recurrent episodes of UTI without a clear evidence of these known risk factors. Recently, a few studies emphasized on idiopathic hypercalciuria (IH) as a predisposing factor for UTI and dysfunctional voiding. [2],[3],[4],[5],[6] Some of these studies have been conducted on patients with recurrent UTI and or urinary tract anatomical abnormalities. On the other hand, idiopathic hypercalciuria is a common finding among referral patients to pediatric nephrologists' offices with chief complaints related to urinary tract other than UTI. Therefore, we carried out a survey to find out whether non-calculus IH is a contributing factor in children with the first attack of pyelonephritis.


   Materials and Methods Top


This is a case-control study carried out on 60 children aged 2-11 years admitted at St Al-Zahra hospital, Isfahan, Iran, with the first episode of upper UTI and 200 age- and gender-matched normal healthy children between September 2003 and February 2005. The sampling method was non-probability convenience sampling. We performed the study on children with first episode of pyelonephritis and without urinary tract abnormalities and/or stones. The likelihood of disease was compared between the two groups.

Inclusion criteria for case group:

1. Children between 2 and 11 years of age.

2. No evidence or past history of kidney stone, urinary tract obstruction and moderate-to-high-grade reflux (low-grade reflux might be under-diagnosed by standard Voiding Cystourethrogram, VCUG)

3. Proven pyelonephritis; diagnosis was made on:



  1. Positive clean-catch or catheter specimens voiding (colony counts more than 100 000 colonies/ml for clean-catch voiding and more than 10 000 colonies/ml for catheter specimen voiding were considered as positive cultures)
  2. Oral temperature >38.5˚C, or rectal temperature >39˚C for children under 5 years plus at least one of the following signs or symptoms:
    • Abdominal pain
    • Dysuria
    • Urinary frequency
    • Urinary urgency
    • Flank pain and or tenderness
  3. And at least one of the following paraclinical findings:
    • Quantitative C-reactive protein (CRP) more than 0.5 mg/dl
    • High erythrocyte sedimentation rate (ESR >30 mm/hr)
    • Low urine specific gravity regarding the patients' hydration


To avoid excessive exposure to radiation, Dimercaptosuccinic acid (DMSA) as diagnostic tool was performed in a small number of patients with a low colony count of microorganisms and or confusing signs and symptoms.

4. Negative urine culture at the time of measuring urine calcium and creatinine and at least 6 weeks after completing the treatment course of pyelonephritis.

5. No documented history of previous UTI.

6. Normal venous blood gas and serum calcium.

7. No history of recent consumption of loop and thiazide diuretics.

We used second fasting spot urine sample to measure calcium and creatinine. Two urine samples were obtained one week apart to increase the accuracy of measurement. All samples were collected after at least 6 weeks of completing the treatment course of pyelonephritis and achieving two consecutive negative cultures in case group. We used adjusted Ca/Cr ratios (mg/mg) (95 th percentile for age) as follows: [7]

  • Age 19 months to 6 years 0.42
  • Age >6 years 0.22


Regarding the age groups mentioned above, patients were divided into two groups: between 2-6 years and more than 6 years up to 11 years.

Urine calcium (uCa, mg/dl) and serum creatinine (sCr, mg/dl) were determined by cresolphthalein and Jaffe method, respectively.

Ultrasound examination and VCUG were performed in all patients before entering the survey as case group to rule out UTO and VUR.

Data was analyzed by SPSS 15 software. To assess risk estimation, odds ratio (95% confidence interval) was used. Considering confounding factors, such as age and gender, we used the Mantel-Haenszel method.


   Results Top


Mean age of case and control group were 4.86 ± 3.08 years and 4.22 ± 2.9 years, respectively. Approximately 83% of case and 58% of control group were female (about 63% of all participants). The mean calcium to creatinine ratio (Ca/Cr) in case and control group were 0.308 ± 0.21 and 0.208 ± 0.12 mg/mg, respectively, P < 0.001. The difference between the mean values of these two groups was significant only in age group ≤6 years, P < 0.0001 and odds ratio was 2.1 (95% CI 1.03-7.8). The mean and percentiles values of urinary Ca/Cr ratio are shown in [Table 1] and [Figure 1], respectively.

After determining the mean values of urine Ca/Cr ration according to both age groups and gender, it was cleared that only significant difference was related to male <6 years [Table 2].

In most patients, ultrasound examination showed hyperechoic kidneys. Only in three cases, mild pelvicaliceal stasis was reported. However, in all patients VCUG could not show reflux. As mentioned above, a few cases of low-grade or intermittent reflux might be underdiagnosed by VCUG.


   Discussion Top


Idiopathic hypercalciuria (IH) is considered as a cause of various lower urinary tract complaints in children. In the pediatric setting, most reports are in favor of non-calculus manifestations of IH more than urolithiasis. [3],[5],[6] A few researches emphasized on the role of hypercalciuria in producing UTI. [2],[4],[8],[9] However, most of these studies were carried out on children with a history of recurrent UTI, abnormalities of urinary tract, urinary tract stones and or dysfunctional voiding. Different mechanisms have been shown as responsible mechanism for UTI, such as uroepithelial damage by calcium oxalate monohydrate, the balance between bacterial virulence and host resistance, an inflammatory response to lipopolysaccharide (LPS) and low urinary secretory IgA (sIgA). [10],[11],[12],[13] Hypercalciuria can predispose patients to UTI due to uroepithelial damage. Akil et al., showed that hypercalciuric rats revealed proliferation and apical cytoplasmic vacuole formation in transitional epithelial cells of bladder and ureter specimens, and also vacuolization of proximal and distal tubules, tubular degeneration, interstitial edema and vasodilatation of the kidney. [10] According to Vachvanichsanong et al., decreasing urinary calcium excretion was associated with decreased symptoms of dysfunctional voiding. [6] Kaminska et al., showed that treatment of pre-urolithiasis state could decrease the recurrence rate of UTI. [8]

The prevalence of idiopathic hypercalciuria is different among various populations; from as low as 0.6% in Japanese to as high as 17.6% in white Americans. [14],[15]

A recent study conducted in Tehran, Iran, showed a prevalence of 5.4% among school-age children. [5]

We found that idiopathic hypercalciuria without any other UTOs could increase the chance of UTI in children less than 6 years of age up to 2.1 times compared to the control group. However, this increment was significant only in male patients. As UTI is not a common disease in male after first year of life, the likelihood of hypercalciuria should be assessed especially in male children with UTI and without any UTOs.

However, the inadequacy of patients in each age-group was the shortage of our study. We recommend more research on larger groups and even longitudinal follow-up studies to clarify the exact role of hypercalciuria in inducing UTI.


   Acknowledgments Top


We would like to express our gratitude to Dr. Ziba Farajzadegan for analyzing our data.

 
   References Top

1.Elder S. Nelson textbook of pediatrics, 17 th ed. Philadelphia: Saunders; 2004. p. 1783-826.  Back to cited text no. 1      
2.Biyikli NK, Alpay H, Guran T. Hypercalciuria and recurrent urinary tract infections: incidence and symptoms in children over 5 years of age. Pediatr Nephrol 2005;20:1435-8.  Back to cited text no. 2      
3.Parekh DJ, Pope JC, Adams MC, Brock JW. The role of hypercalciuria in a subgroup of dysfunctional voiding syndromes of childhood. J Urol 2000;164:1008-10.  Back to cited text no. 3      
4.Lopez MM, Castillo LA, Chavez JB, Ramones C. Hypercalciuria and recurrent urinary tract infection in Venezuelan children. Pediatr Nephrol 1999;13:433-7.  Back to cited text no. 4      
5.Esfahani ST, Madani A, Siadati AA, Nabavi M. Prevalence and symptoms of idiopathic hypercalciuria in primary school children of Tehran. Iran J Pediatr 2007;17:353-8.  Back to cited text no. 5      
6.Vachvanichsanong P, Malagon M, Moore ES. Urinary incontinence due to idiopathic hypercalciuria in children. J Urol 1994;152:1226-8.  Back to cited text no. 6      
7.Sparrow MM. The Harriet lane hand book, 16 th ed. Philadelphia: Mosby; 2002. p. 397-416  Back to cited text no. 7      
8.Kaminska A, Jung A. Results of the treatment of pre-urolithiasis state in children with recurrent urinary tract infections. Pol Merkuriusz Lek 2000;8:209-10.  Back to cited text no. 8      
9.Stojanovic VD, Milosevic BO, Djapic MB, Bubalo JD. Idiopathic hypercalciuria associated with urinary tract infection in children. Pediatr Nephrol 2007;22:1291-5.  Back to cited text no. 9      
10.Akil I, Kavukcu S, Inan S, Yilmaz O, Atilla P, Islekel H, et al. Evaluation of histologic changes in the urinary tract of hypercalciuric rats. Pediatr Nephrol 2006;21:1681-9.  Back to cited text no. 10      
11.Svanborg-Eden C, De Man P, Jodal U, Linder h, Lomberg H. Host parasite interaction in urinary tract infection. Pediatr Nephrol 1987;1:623-31.  Back to cited text no. 11      
12.Shahin RD, Engberg I, Hegberg L, Svanborg-Eden C. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram negative infection. J Immunol 1995;144:3475-80.  Back to cited text no. 12      
13.Fliedner M, Mehls O, Rautberg EW, Ritz E. Urinary IgA in children with urinary tract infection. J Pediatr 1986;109:416-21.  Back to cited text no. 13      
14.Kaneko K, Tsuchiya K, Kawamura R, Ohtomo Y, Shimizu T, Yamashiro Y, et al. Low prevalence of hypercalciuria in Japanese children. Nephron 2002;91:439-43.  Back to cited text no. 14      
15.O'Brien KO, Abrams SA, Stuff JE, Liang LK, Welch TR. Variables related to urinary calcium excretion in young girls. J Pediatr Gastroenterol Nutr 1996;23:8-12  Back to cited text no. 15      


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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