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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 1  |  Page : 31-35

Hypercalciuria and nocturnal enuresis, what is the relation?


1 Department of Pediatrics, Faculty of Medicine, Minia University, El Minia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Minia University, El Minia, Egypt

Date of Submission18-Nov-2019
Date of Decision25-Nov-2019
Date of Acceptance21-Dec-2019
Date of Web Publication26-Jun-2020

Correspondence Address:
MD Salwa H Swelam
Department of Pediatrics, Faculty of Medicine, Minia University, El Minia, 61511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJOP.AJOP_12_20

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  Abstract 


Background Nocturnal enuresis (NE) is a multifactorial disease and is a common problem in children. Monosymptomatic NE is defined as a normal void occurring at night in bed in the absence of any other symptoms referable to the urogenital tract, and it precludes any daytime symptomatology.
Aim The aim of the study was to detect the prevalence and the association of NE and hypercalciuria in patients who have primary NE for better evaluation and management.
Patients and methods This cross-sectional study included 200 children in an age range of 7–12 years classified into two groups: Group I cases included 100 children with primary NE and group II included 100 healthy control children age-matched and sex-matched with the previous group. Both groups were subjected to complete history taking, thorough clinical examination, and laboratory investigations including determining the urine calcium/creatinine ratio.
Results According to the result urine calcium/creatinine ratio was elevated in NE patients than control ones (0.16 vs 0.14) in cases and control groups, respectively.
Conclusion Urine calcium/creatinine ratio was elevated in nocturnal enuretic patients with the that there is association between NE and hypercalciuria.

Keywords: hypercalcuria, monosymptomatic, nocturnal enuresis


How to cite this article:
Sayed SZ, Swelam SH, Kamel HM, Elfakhry HA. Hypercalciuria and nocturnal enuresis, what is the relation?. Alex J Pediatr 2020;33:31-5

How to cite this URL:
Sayed SZ, Swelam SH, Kamel HM, Elfakhry HA. Hypercalciuria and nocturnal enuresis, what is the relation?. Alex J Pediatr [serial online] 2020 [cited 2020 Oct 30];33:31-5. Available from: http://www.ajp.eg.net/text.asp?2020/33/1/31/287726




  Introduction Top


Enuresis which is synonymous with intermittent nocturnal incontinence is discrete episodes of urinary incontinence during sleep in children greater than or equal, to 5 years of age. Monosymptomatic enuresis means enuresis without any other lower urinary tract symptoms and without a history of bladder dysfunction [1]. Nonmonosymptomatic enuresis means enuresis in children with other lower urinary tract symptoms, for example, increased frequency, daytime incontinence, urgency, genital, or lower urinary tract pain [1]. Primary nocturnal enuresis (NE) is caused by a disparity between capacity of bladder and nocturnal urine production and the child’s failure to awaken in response to a full bladder [1]. A small subgroup of children with primary NE has little or no arousal to bladder distention and exhibit uninhibited bladder contractions before voiding (i.e. detrusor-dependent enuresis) [2]. In general, the goal of NE treatment will include decreasing the total number of enuretic nights, avoiding enuresis on specific nights in specific locations, stress reduction for the child and family, and the avoidance of NE recurrence [3]. Combining enuresis alarms with other behavioral modalities enhances treatment success [4]. Pharmacologic therapies are not curative, but they reduce the frequency of enuresis or temporarily resolve symptoms over time until spontaneous resolution occurs [1]. In addition to alarm therapy, desmopressin therapy is recommended as first-line treatment for patients with primary monosymptomatic NE. Anticholinergic medications such as oxybutynin (Ditropan) have been used to treat urinary urgency, frequency, and incontinence [5]. For children with NE refractory to behavioral therapy, desmopressin, and anticholinergic therapy imipramine (tricyclic antidepressant) is recommended [5]. Hypercalciuria, or excessive urinary calcium excretion, is the most common identifiable cause of calcium stone in the kidneys [6]. In children, hypercalciuria is often associated with some degree of hematuria and back or abdominal pain and is also sometimes associated with voiding symptoms [6].

Aim of the study was to detect the prevalence and the association of NE and hypercalciuria in patients who have primary NE for better evaluation and management.


  Patients and methods Top


This study included 200 children in the age range of 7–12 years, 100 with primary NE and 100 apparently healthy children serving as healthy control matched in age and sex. Enuretic children were selected from the Pediatrics Nephrology Clinic and the Urology Clinic at El Minia University Hospital, El Minia, Egypt in the period from May to November 2017.

The study was conducted according to the principles of Helsinki Declaration and agreed by the Faculty of Medicine, Minia University, Ethical Committee (No: 116-5-2016). Informed written consents from the patient’s caregiver were obtained. Written consents were obtained from patients’ caregivers for patients of less than 16 years old.

They were classified into Group I and group II. Group I included 100 children complaining of primary NE. Group II included 100 children taken as a healthy control group and they were age and sex matched.

Enuretic children with vesicoureteral reflux, history of urinary tract infection during the last month, nutrition with ketogenic diet or any treatment with corticosteroids, or diuretics in the last month, or high-dose vitamin D in the last 6 months (medications like drops, syrup, or ampoule), children who suffered from major fracture in lower extremities or bed rest for a long time, children with symptoms (including urgency, frequency, dysuria) or abdominal pain or untreated constipation (to avoid coincidence of above-mentioned urinary symptoms) and children usually wearing tight pants (this may predispose children to develop urinary symptoms or urinary tract infection), or children who did not undergo circumcision all were excluded. Control groups were chosen to have healthy children with matched age and sex with the study group. The study and healthy control groups included in the study were subjected to complete history taking and thorough clinical examination. They were also subjected to laboratory investigations including determining the urine calcium/creatinine ratio, spot urinary calcium-to-creatinine ratios (mg/mg) (usually collected from fasting second-void morning urine specimens urine specimens). Young children and infants tend to have higher urinary calcium excretion and lower urinary creatinine levels, so the suggested normal limits for calcium/creatinine ratios differ by age as follows [7]:
  1. Up to 6months of age: less than 0.8.
  2. From 6 to 12 months of age: less than 0.6.
  3. 24 months and older: less than 0.2 [7].


Patients with hypercalciuria were investigated for the etiology of their hypercalciuria via blood samples including measuring alkaline phosphatase, phosphorus, calcium, potassium, sodium, blood urea nitrogen, and serum creatinine.

Statistical analysis

The numerical data were presented as means and standard deviations while non-numerical data were presented as percentage. Two-tailed t-tests were used to analyze the differences between the control and patient groups. P values less than 0.05 were considered statistically significant. The magnitude of correlations was determined by Pearson’s correlation coefficient. All the data were analyzed by the Statistical Package Prism 3.0 (Graph Pad software, San Diego, California, USA). Figures were done by Microsoft Office Excel 2007 applications shown on Windows Vista Germany.


  Results Top


Both groups were of matched age and sex ([Table 1]).
Table 1 Demographic data of studied groups

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There was a significant higher difference as regards potassium, phosphorus levels, and urine calcium/creatinine ratio in the study group when matched with healthy control groups but insignificant difference as regards sodium and calcium between both groups ([Table 2]).
Table 2 Comparison between patients and control group regarding laboratory data

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As regards hypercalciuria in the study and control groups, there was statistically significant difference between the two groups ([Table 3]).
Table 3 Comparison between nocturnal enuresis and healthy control group regarding hypercalciuria (Ur. Ca/Cr ratio >0.21)

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Also, there was statistically significant difference between the both groups as regards urine calcium/creatinine ratio in cases with and without hypercalciuria ([Table 4]).
Table 4 Comparison regarding Ur. Ca/Cr ratio in nocturnal enuresis cases with and without hypercalciuria

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In comparison between patients and healthy control groups regarding correlation between urine calcium/ creatinine ratio and serum creatinine there was statistically significant difference between the two groups ([Table 5]).
Table 5 Correlation between nocturnal enuresis cases and control group regarding Ur. Ca/Cr ratio and serum Ca

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Seventy-eight percent in the study group had no hypercalciuria and 22% had hypercalciuria while in the control group 47% had no hypercalciuria and 6% had hypercalciuria ([Table 3]).

Seventy-eight percent of the enuretic children did not have hypercalciuria and only 22% of them were hypercalciuric, while 94% of the control group did not have hypercalciuria and 6% of them were hypercalciuric ([Figure 1]).
Figure 1 Prevalence of hypercalciuria among nocturnal enuresis and healthy control groups.

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  Discussion Top


Hypercalciuria has been defined in children on a ‘statistical’ basis as urinary calcium excretion of more than 4 mg/kg/day as opposed to the ‘outcome’-based value of more than 250 mg/day in women and more than 300 mg/day in men [8],[9],[10].

Nevéus et al. [11] was the first to propose that hypercalciuria can be considered as an important pathogenic factor of NE and noted that enuretic children had absorptive hypercalciuria.

Other pathogenic factors that have been suggested are nocturnal desmopressin deficiency, disorder of circadian rhythm of renal functions (sodium and osmotic excretion), dysregulation of prostaglandins, excretion, etc. Additionally, hypercalciuria is a newly proposed factor that has a correlation with NE [12],[13].

This prospective study included 200 children in the age range of 7–12 years and were classified into two groups: Group I included 100 children with primary NE and group II included 100 healthy control children with matched age and sex with the previous group. The aim of this study was to find the association between NE and hypercalciuria. The present study demonstrated that urine calcium/creatinine ratio was elevated in NE patients than control ones (0.16 vs 0.14) in cases and control groups, respectively. These results were in agreement with Valavi Ehsan et al. [13] who found that urine calcium/creatinine ratio was higher in NE patients 3.04 vs 2.57, respectively.

Regarding the results of hypercalciuria frequency, the results showed that hypercalciuria is significantly more frequent in the NE patient group than the control group (22 cases in the NE group ‘22.0%’ vs six cases ‘6.0%’ in the control group). These results agreed with the findings of Valavi Ehsan et al. [13] who studied the clinical correlation between hypercalciuria and nocturnal enuresis. They found that hypercalciuria was found in 26 (21.3%) of the NE patients as compared with five (4.5%) of 110 normal children (P<0.001).

These results may be expressed by the fact that hypercalciuria has a pivotal role in NE, as it is significantly associated with low ADH levels and nocturnal polyuria as it was reported by Abu Salem Mahmoud et al. and Fallahzadeh et al. [1],[14].

In partial agreement with the current study, Nikibakhsh et al. [15] found that 12 (10.1%) patients in the NE group had hypercalciuria (which is less than our results) and also Azhir et al. [5] in Iran reported the prevalence of hypercalciuria among children with enuresis to be 9.2%. On the other hand, Raes et al. [16] evaluated the incidence of hypercalciuria, defined as urinary calcium-to-creatinine ratio greater than 0.21 mg/mg, in children with NE. They found that of the children with NE 12% had 24 h hypercalciuria. Also, they observed a significant correlation between calcium excretion and nocturnal polyuria, low urinary osmolality and increased sodium and osmolar excretion in the nighttime urine sampling. In addition, Civilibal et al. [17] found that hypercalciuria was found in 27 (23%) of the monosymptomatic NE patients compared with two (4%) of normal children (P<0.001).

The present results have shown that there were significant differences as regards potassium, phosphorus levels, and urinary calcium/creatinine ratio between study and control groups but insignificant difference as regards sodium and calcium between both groups. These results were in contrast to Nikibakhsh et al. [15] who found that all 15 hypercalciuric patients had normal serum Ca, P, Na, and K as compared with non-hypercalciuric ones. Also, similar findings were noticed by Azhir et al. [5] and Civilibal et al. [17].

Regarding urine calcium/creatinine ratio in patients with and without hypercalciuria, there was statistically significant difference between the both (P<0.001*) also in comparison between patients and control groups regarding urine calcium/creatinine ratio* Ca there was statistically significant correlation between the two groups (patients and control groups). Also, similar findings were reported by Azhir et al. [5].


  Conclusion Top


Urine calcium/creatinine ratio was elevated in nocturnal enuretic patients and we concluded that there is an association between NE and hypercalciuria.

Recommendations

From this study, it was recommended that adding the measurement of urine calcium level in patients with NE in the process of looking for etiologies, based on accompanying enuresis and hypercalciuria, its therapeutic approach may need to be changed and more studies should be done considering the controversy which exists about the role of hypercalciuria in the pathogenesis of NE.

Acknowledgements

The study could not revise the diet of the studied groups for excessive sodium consumption.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

M.A., L.A., A.M., and S.H. participated in the study design, data collection and interpretation and wrote the manuscript; A.M. and N.A. analyzed the immunological data and S.H., L.A., and M.A. participated to discuss the results and to write the manuscript; M.A. supervised the research group; all authors listed in the manuscript have contributed substantially to the study and have revised and approved the submitted version.

The research was supported by El Minia Faculty of Medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Abu Salem Mahmoud E, El-Shazly HM, Al-Zahraa A. Hassan.Nocturnal enuresis among primary school children in Zarka district, Damietta governorate. Egypt Menoufia Med J 2016; 29:1025–1032.  Back to cited text no. 1
    
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Azhir A, Nasseri F, Fazel A, Adibi A, Frajzadegan Z, Divband AH. Etiology and pathology of enuresis among primary school children in Isfahan, Iran. Saudi Med J 2007; 28:1706–1710.  Back to cited text no. 5
    
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Baek M, Park K, Lee HE, Kang JH, Suh HJ, Kim JH et al. A nationwide epidemiological study of nocturnal enuresis in korean adolescents and adults: population based cross sectional study. J Korean Med Sci 2013; 28:1065–1070.  Back to cited text no. 6
    
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Vieira MS, Francisco PC, Hallal ALLC, Penido MGMG, Bresolin NL. Association between dietary pattern and metabolic disorders in children and adolescents with urolithiasis. J Pediatr (Rio J) 2019; 5:pii.  Back to cited text no. 7
    
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Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR. Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009; 94:351–365.  Back to cited text no. 8
    
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Stojanovic VD, Milosevic BO, Djapic MB, Bubalo JD. Idiopathic hypercalciuria associated with urinary tract infection in children. Pediatr Nephrol 2007; 22:1291–1295.  Back to cited text no. 9
    
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Sureshkumar P, Jones M, Caldwell PH. Risk factors for nocturnal enuresis in school-age children. J Urol 2009; 182:2893–2899.  Back to cited text no. 10
    
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Nevéus T, vonGontard A, Hoebeke P. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006; 176:314–324.  Back to cited text no. 11
    
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Ehsan V, Ahmadzadeh A, Hooman N, Aminzadeh M. Clinical correlation between hypercalciuria and nocturnal enuresis. Saudi J Kidney Dis Transpl 2011; 22:976–981.  Back to cited text no. 13
    
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Fallahzadeh MK, Fallahzadeh MH, Mowla A, Derakhshan A. Hypercalciuria in children with urinary tract symptoms. Saudi J Kidney Dis Transpl 2010; 21:673–677.  Back to cited text no. 14
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Nikibakhsh A, Poostindooz H, Mahmoodzadeh H, Karamyyar M, Rasoul Ghareaghaji R, Sepehrvand N. Is there any correlation between hypercalciuria and nocturnal enuresis? Indian J Nephrol 2012; 22:88–93.  Back to cited text no. 15
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Civilibal M, SelcukDuru N, Elevli M, Civilibal N. Hypercalciuria in children with monosymptomatic nocturnal enuresis. J Pediatr Urol 2014;10:1145–1148.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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