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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2011  |  Volume : 22  |  Issue : 1  |  Page : 79-82
Determination and comparison of mean random urine calcium between children with vesicoureteral reflux and those with improved vesicoureteral reflux

Department of Pediatric, Guilan University of Medical Sience, Rasht, Iran

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Date of Web Publication30-Dec-2010


Urinary reflux can cause irreversible complications such as reflux nephropathy and ESRD. Diagnostic imaging such as voiding cystourethrogram (VCUG) is invasive and causes irradiation. Several studies have shown that markers such as urine IL-8 or serum Procalcitonin might be useful for the diagnosis of vesico-ureteral reflux (VUR) as a substitution for invasive methods. The aim of this study was to determine and compare the mean urine Ca/Cr ratio and hypercalciuria between two groups of children aged 2-10 years affected by VUR. This is a cross-sectional study in which 32 chil­dren having the following entrance criteria were included: children 2-10 years old not affected by uri­nary tract infection during the last three months and their reflux or recovery having been diagnosed by VCUG or direct radionuclide cystography, divided into two groups of affected by reflux and recovered from reflux. Then, the point urine specimens were collected with permission of their parents in a single laboratory and urine Ca and Cr for each specimen were measured. The Ca/Cr ratio was calculated for each child to evaluate Ca excretion from the urine, which was possible without collecting the 24-hours urine. The Ca/Cr ratio mean and the hypercalciuria were compared between the groups. To analyze our data, the Mann-Whiney test and the Chi-square test were used, using SPSS V.15. Thirty-two children, including 18 children recovered from reflux and 14 affected by reflux, were entered in our study. The Ca/Cr ratio mean was 0.692 ± 1.874 for the affected and 0.118 ± 0.187 for the recovered group. The Ca/Cr ratio mean for the affected male and female groups was 0.012 ± 0.008 and 0.805 ± 1.0913, respectively. This amount was 0.0175 ± 0.01767 for the recovered male and 0.131 ± 0.195 for the recovered female group. There was no significant statistical difference between the groups with res­pect to the Ca/Cr ratio mean, but there was a significant statistical difference between the two groups of females (P-value = 0.026). Also, there was no significant statistical difference between the two groups of males relative frequency of hypercalciuria was significantly higher in the group affected by reflux than in the recovered from reflux group (P-value = 0.017). Urine Ca excretion is elevated in children with reflux, and may be more useful as an appropriate marker for the diagnosis of VUR than other invasive methods.

How to cite this article:
Badeli H, Sadeghi M, Shafe O, Khoshnevis T, Heidarzadeh A. Determination and comparison of mean random urine calcium between children with vesicoureteral reflux and those with improved vesicoureteral reflux. Saudi J Kidney Dis Transpl 2011;22:79-82

How to cite this URL:
Badeli H, Sadeghi M, Shafe O, Khoshnevis T, Heidarzadeh A. Determination and comparison of mean random urine calcium between children with vesicoureteral reflux and those with improved vesicoureteral reflux. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2021 May 17];22:79-82. Available from: https://www.sjkdt.org/text.asp?2011/22/1/79/74357

   Introduction Top

Vesico-ureteral reflux (VUR) is the backward flow of urine from the bladder into the ureter, with an incidence of 1-2% during childhood. [1] Thirty percent to 60% of children with VUR have some degrees of renal injury. [2] The most common chronic complication of VUR is HTN, whose incidence is around 10-20% in long­term studies. Also, 15% the of patients with reflux nephropathy become ESRD ultimately. [3],[4] Therefore, all of the children below eight years of age with urinary tract infections (UTI) should undergo voiding cystourethrogram (VCUG). VCUG is the best measure for the diagnosis of VUR. [5] But, it is technically difficult [6] and can cause exposure to irradiation and result in UTI. [7] Because of these complications, easier and less-invasive methods seem to be bene­ficial and useful. Data in recent years have proposed that VUR by itself and without uri­nary tract infection is an inflammatory pro­cess. Galanakis and colleagues suggest that the inflammatory process in VUR is ongoing even after the UTI has resolved. [8] Procalcitonin (PCT) is the prohormone of calcitonin and is cleaved by proteolytic enzyme into active hormone. Circulating levels of PCT in healthy subjects are below the detection limit. But, the serum level of PCT is elevated during inflammatory states. [9] Calcitonin can reduce the Ca level of serum by excreting Ca from renal tubules and the gastrointestinal tract. Leory et al reported that the serum PCT level would be elevated du­ring VUR. [10] Garcia-Nieto and colleagues found that children with VUR had a higher incidence of hypercalciuria compared with those without VUR. [11] With the above-mentioned information about PCT, if vesicoureteral reflux can con­tinue kidney inflammation, then comparing its effect on Ca handling (such as increased uri­nary calcium content) may help in the diagno­sis of possible reflux. The aim of our study is to compare the mean urine Ca and the relative frequency of hypercalciuria between two groups of children: children with urinary reflux and children with improved urinary reflux, to find an easier and non-invasive method for the diagnosis and follow-up of VUR in children.

   Subjects and Methods Top

In this cross-sectional study, we compared the mean non-fasting single-spot urine Ca and creatinine ratio of 32 children with VUR (group A) and improved VUR (group B). All children were between two to ten years old, without UTI during the last three months, no urologic abnormalities and VUR or their improvement was documented by direct radionuclide cysto­graphy (DRNC) or VCUG.

A single laboratory measured all urine Ca and Cr levels. They used special kits for Ca and Cr. The measuring machine was a "Hitachi auto analyzer". The "Alcion" technique was used for Ca with (precision) CV = 1.3% and the "Jaffe" technique was used for Cr with (precision) CV = 2.3%.

Information such as age, sex and unilateral or bilateral reflux was extracted from the files of children. To analyze the data, SPSS version 15 software was used. Also, for comparing the mean urine Ca between the two groups, Mann- Whitney test, and for comparing the relative frequency of hypercalciuria between the groups, Chi-square test, were used.

Hypercalciuria was considered as a Ca/Cr (mg/mg) ratio higher than 0.2 for children over two years old. The ethics committees of our university approved this study.

   Results Top

Thirty-two children were evaluated. The mean age was 5.8 ± 2.13 years (four males and 28 females). Fourteen children had reflux (group A), with a mean age of 4.85 ± 1.79 years (two males and 12 females), and the remaining chil­dren had improved reflux (group B; 18), with a mean age of 5.9 ± 2.29 years (two males and 16 females). In group A, the mean age of the first UTI was 31.7 ± 2.4 months and the mean duration between diagnosis of reflux and ente­ring into this study was 30 ± 9.1 months. In group B, the mean age of the first UTI was 27 ± 2.04 months and the mean duration between diagnosis of reflux and recovery from reflux was 19.9 ± 1.3 months.

The severity of reflux was defined by VCUG or DRNC and then divided into three stages: mild, moderate and severe (grades 1 and 2 were considered as mild, grade 3 was considered as moderate and grades 4 and 5 were considered as severe stage).

In group A, seven children (50%) had mild, four children (28.6%) had moderate and three children (21.4%) had severe reflux; six of the children in this group (42.9%) had bilateral reflux and eight of them (57.1%) had unilateral reflux according to the last radiological assess­ments.

In group B, eight children (44.4%) had mild, three children (16.6%) had moderate and seven children (38.8%) had severe reflux. Thirteen children of group B (72.2%) had bilateral re­flux and the rest of them had unilateral reflux according to radiological assessments that were done before recovery.

Renal scars were evaluated by DMSA scan for all the children. There were four children with renal scars diagnosed by DMSA scan, and three of them belonged to group A. The Ca/Cr ratio was 0.692 ± 1.847 for group A and 0.118 ± 0.187 for group B [Figure 1].
Figure 1: Distribution of urine Ca/Cr ratio and the limitation of mean of the urine Ca/Cr ratio for the two
groups. The horizontal line shows that the urine Ca/Cr level equals 0.2 to define hypercalciuria.

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Because the data did not have a normal distri­bution, non-parametric tests (Mann-Whitney test) was used for comparison of the urine Ca mean between the two groups.

The statistical analysis has shown that there is no significant statistical difference for the Ca/Cr ratio between the two groups. The Ca/Cr ratio mean among males of group A was 0.012 ± 0.008 and of group B was 0.0175 ± 0.0176. Also, this amount among females of group A was 0.805 ± 1.913 and of group B was 0.131 ± 0.195.

After statistical comparison of the Ca/Cr ratio between males and females of each group, we did not find a significant statistical difference between males of the two groups, but there was a significant statistical difference between the two groups of females (P = 0.026).

Despite there being no significant difference between the Ca/Cr ratio mean between the two groups, the relative frequency of hypercalciuria was significantly greater for group A than for group B (P = 0.017). Comparing the relative frequency of hypercalciuria between females of each group, we found that it was significantly greater in females of group A than those of group B (P = 0.01).

   Discussion Top

VUR occurs during childhood, with a preva­lence of 1-2%, and can lead to reflux neph­ropathy, HTN and ESRD. The most important presentation of VUR is UTI and, therefore, radiological surveillance (VCUG or DRNC) of children below five years of age after the first febrile UTI is mandated. These diagnostic methods are invasive and can cause irradiation and UTI. To date, several attempts were made to replace the non-invasive method with VCUG or DRNC. Different substances have been fol­lowed in urine for this aim, such as IL-6 and soluble TNF receptor-1. [12] Although researchers such as Smellie [4] believe that sterile reflux can­not harm the kidneys, Galanakis and colleagues suggest that inflammatory processes in the VUR is ongoing even after the UTI has re­solved. Their supporting evidence was that urine IL-8 levels remain elevated in infants with VUR even in the absence of a UTI. [8]

The serum PCT level can increase during the inflammatory states, which causes increased excretion of Ca from the renal tubules. Garcia Nieto et al reported that the prevalence of hypercalciuria in children with reflux was 58.6%, which is significantly greater than that in the general pediatric population.

The prevalence of hypercalciuria in different studies in the general pediatric population was reported at 3.8%, [13] 2.2% and 3%. [14]

With this background, we performed our study to elucidate the calcium excretion difference in the group with VUR and in the group with improved from VUR. The mean Ca/Cr ratio has had no significant difference between the two groups, but the relative frequency of hypercalciuria in group A (57.143%) was sig­nificantly greater than that group B (16.67%) (P = 0.017). Our finding was similar to that of the Garcia Nieto et al study. Our study simi­larly demonstrated that hypercalciuria is more common in patients with VUR, which dec­reased with recovery of VUR.

In conclusion, elevated urine Ca might be an appropriate marker for the diagnosis of VUR if there was no simultaneous UTI. To determine the exact mechanism of hypercalciuria in VUR, more studies need to evaluate hormones or mediators that can cause hypercalciuria in patients with VUR thus providing a non-in­vasive approach to diagnose VUR.

   Acknowledgment Top

The authors wish to acknowledge and thank their patients and their parents because with­out them they could not have been able to per­form this study. Also, the authors would like to thank Ms. L.M. Nabizadeh and the staff of Guilan Reference Laboratory for their excel­lent logistic support for this study.

   References Top

1.Chand DH, Rhoades T, Poe SA. Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis. J Urol 2003;170(4.2):1548-50.  Back to cited text no. 1
2.Arant BS Jr. Vesicoureteric reflux and renal injury. Am J Kidney Dis 1991;17(5):491-511.  Back to cited text no. 2
3.Smellie JM, Prescod NP, Shaw PJ, Risdon RA, Bryant TN. Childhood reflux and urinary infec­tion: A follow-up of 10-41 years in 226 adults. Pediatr Nephrol 1998;12(9):727-36.  Back to cited text no. 3
4.Jacobson SH, Eklof O, Lins LE, Wikstad I, Winberg J. Long-term prognosis of post-infec­tious renal scarring in relation to radiological findings in childhood: A 27 year follow-up. Pediatr Nephrol 1992;6(1):19-24.  Back to cited text no. 4
5.Blumenthal L. Vesicoureteral reflux and urinary tract infection in children. Postgrad Med J 2006; 82(963):31-5.  Back to cited text no. 5
6.Hellstrom M, Jacobsson B. Diagnosis of vesico­ureteric reflux. Acta Paediatr 1999;88(431):3-12.  Back to cited text no. 6
7.Maskell R, Pead L, Vinnicombe J. Urinary infec­tion after micturating cystography. Lancet 1978; 2(8101):1191-2.  Back to cited text no. 7
8.Galanakis E, Bitsori M, Dimitriou H, Giannakopoulou C, Karkavitsas NS, Kalmanti M. Urine Interleukin-8 as a marker of vesicoureteral refluxe in infants. Pediatrics 2006;117(5):e863-7.  Back to cited text no. 8
9.Level C, Chauveau P, Delmas Y, et al. Procalci­tonin: A new marker of inflammation in haemo­dialysis patients. Nephrol Dial Transplant 2001; 16(5):980-6.  Back to cited text no. 9
10.Leroy S, Romanello C, Galetto Lacour A, et al. Procalcitonin to reduce the number of unecessary cystographics with aurinary tract infection: A European validation study. J Pediatr 2007;150(1): 89-95.  Back to cited text no. 10
11.Garcia-Nieto V, Siverio B, Monge M, Toledo C, Molini N. Urinary Calcium excretion in children with vesico-ureteral reflux. Nephrol Dial Tranplant 2003;18(3):507-11.  Back to cited text no. 11
12.Ninan G, Jutley R, Eremin O. Urinary cytokines as markers of reflux nephropathy. J Urol 1999; 162(5):1739-42.  Back to cited text no. 12
13.Melian JS, Garcia-Nieto V, Sosa AM. Inheritance and prevalence of hypercalciuria in the children from the island of La Glomera. Nefrologia 2000; 20(6):510-6.  Back to cited text no. 13
14.Moore ES, Coe FL, McMann BJ, Favus MJ. Idiopathic hypercalciuria in children: Prevalence and metabolic characteristics. J Pediatr 1978;92 (6):906-10.  Back to cited text no. 14

Correspondence Address:
Hamidreza Badeli
Department of Pediatric, Guilan University of Medical Science, Rasht
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PMID: 21196618

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