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and&#47;or with a family history of urolithiasis&#44; would have increased susceptibility to have a kidney development abnormality&#46; These children also inherit hypercalciuria that could also favor formation of kidney stones&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The present study was conducted to find out if children with unilateral renal agenesis &#40;URA&#41; have a higher prevalence of hypercalciuria&#44; hypocitraturia and&#47;or a familiar history of urolithiasis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This descriptive and multicenter study included 67 children &#40;43 males&#44; 24 females&#41; with URA who were reviewed at Spanish Pediatric Nephrology Units of &#8220;Hospital Nuestra Se&#241;ora de Candelaria&#8221; &#40;Tenerife&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#41;&#44; &#8220;Hospital Universitari Sant Joan de Reus&#8221; &#40;Tarragona&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#44; &#8220;Hospital de Fuenlabrada&#8221; &#40;Madrid&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; and &#8220;Hospital General Universitario Santa Luc&#237;a&#8221; &#40;Cartagena&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46; The age at the time of the study was 10&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;84 years &#40;range&#58; 0&#46;16&#8211;21&#46;5&#41;&#46; The patients were controlled in each hospital from the postnatal ultrasound confirmation of the diagnosis of URA that had performed in utero&#44; i&#46;e&#46; since the first weeks of life&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">URA was located on the left side in 41 cases&#44; and on the right side in 26&#46; The diagnosis of URA was made by means of renal ultrasound and DMSA scan&#46; URA was associated with vesicoureteral reflux in three patients&#46; No other urinary tract malformations were found&#46; None of them had nephrocalcinosis or renal dysplasia morphological signs&#46; During follow-up&#44; 27 children suffered from urinary tract infections&#46; All patients were free of infection at the time of simple urine collection&#46; None of the patients were diagnosed with chronic renal failure&#46; None of the children showed elevated levels of plasma creatinine&#44; hypertension&#44; or signs of distal renal tubular acidosis&#46; We asked parents and&#47;or other relatives about family history of urolithiasis of the 67 children&#46; There was no background of consanguinity in the family histories&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The urine collected corresponded to non-fasting samples in which calcium&#44; citrate and creatinine were determined&#46; In accordance with criteria set by the <span class="elsevierStyleItalic">Spanish Paediatric Nephrology Association</span>&#44; hypercalciuria is diagnosed in children between 1 and 2 years of age when the calcium&#47;creatinine ratio &#40;UCa&#47;UCr&#41; from two individual&#44; consecutive measures is greater than 0&#46;47<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a> Based on the results of So et al&#46;&#44; hypercalciuria in children between 2 and 4 years of age was diagnosed when UCa&#47;UCr was greater than 0&#46;28<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> In children older than 4 years of age&#44; the diagnosis of hypercalciuria was made when the UCa&#47;UCr was greater than 0&#46;20<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> a value that corresponds to the 95th percentile of a sample made up of 100 healthy children&#44; from a previous study conducted by one of our groups&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> Based on Stapleton and Kroovand&#39;s criteria&#44; the hypocitraturia diagnosis criterion is a citrate&#47;creatinine ratio less than 400<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> In patients older than 14 years&#44; the hypocitraturia diagnosis criterion is a citrate&#47;creatinine ratio less than 250<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The UCa&#47;UCr ratio in non-fasting single spot urine was measured&#44; in addition&#44; to the parents of 29&#47;68 of the patients without changing their diets&#46; In these adults&#44; hypercalciuria was diagnosed when UCa&#47;UCr was higher than 0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#44; according to the average value previously found in our adult population from previous study conducted by one of our groups &#40;UCa&#47;UCr<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The results of urinary concentration test and urinary elimination of albumin were collected from the medical records&#46; The normal values used as reference to the maximum urine osmolality<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> and the albumin&#47;creatinine ratio<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> have been previously published&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The frequency of family history of urolithiasis in parents and other relatives of our URA patients was compared with a historical control group conducted in one of the hospitals participating in the study&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Analytical procedures and renal function tests</span><p id="par0050" class="elsevierStylePara elsevierViewall">In the laboratories of each of the hospitals participating in the study&#44; urinary creatinine was determined by the creatininase method&#44; calcium was measured by photometric assay&#44; urinary citrate was assessed by the citrate lyase method and urinary albumin was measured by a nephelometric technique &#40;Array&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Renal concentrating capacity was determined after administration of 20<span class="elsevierStyleHsp" style=""></span>&#956;g of desmopressin intranasal or 0&#46;12<span class="elsevierStyleHsp" style=""></span>mg &#40;120<span class="elsevierStyleHsp" style=""></span>&#956;g&#41; of oral desmopressin lyophilisate &#40;MELT&#41; that dissolves immediately in the mouth&#46; After emptying the bladder three urine samples were collected at 90<span class="elsevierStyleHsp" style=""></span>min intervals&#46; The highest osmolality value obtained was taken as the test result&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> Urinary osmolality was determined by measuring the freezing point depression in an Osmostat Osmometer &#40;Menarini&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical methods</span><p id="par0060" class="elsevierStylePara elsevierViewall">Kolmogorov&#8211;Smirnov test was used to study the distribution of the variables&#46; When they fit a normal distribution&#44; a notation of average value and standard deviation is used&#46; The other quantitative variables were expressed in terms of median and interquartile ranges&#46; Basic statistics were performed using SPSS statistical software &#40;SPSS V 19&#46;0&#44; SPSS Inc&#46;&#44; USA&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All of the procedures and protocols followed during this study meet the ethical&#44; administrative&#44; and data protection requirements imposed by the Paediatrics Departments of the hospitals participants&#44; which are established in accordance with the law of Spain&#46; All parents gave informed consent&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Metabolic disorder was observed in 26 children&#58; hypercalciuria in 16 children &#40;11M&#44; 5F&#41;&#44; hypocitraturia in 9 cases &#40;5M&#44; 4F&#41; and both hypercalciuria and hypocitraturia in one patient&#46; Thereby we observed any risk of lithiasis in 38&#46;8&#37; of children with URA&#46; Eight children &#40;11&#46;9&#37;&#41; suffered renal colic during follow-up &#40;four with hypercalciuria and four with hypocitraturia&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the values of the studied parameters as well as the percentage of children with metabolic or functional anomalies&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The familial history of urolithiasis was found in 42&#47;67 children &#40;62&#46;7&#37;&#41;&#58; 12 in the first-degree&#44; 15 in the second degree and in 15 patients both in the first and second degree relatives&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Familial history of urolithiasis and the concomitant existence of hypercalciuria and&#47;or hypocitraturia in patients with URA were observed in 19 families&#46; In another 23 families only history of urolithiasis existed in children&#39;s relatives&#46; In another 7 families the patients were carriers of metabolic anomalies potentially causing kidney stones&#46; In 23 additional families&#44; only history of urolithiasis existed in children&#39;s relatives&#46; In 7 additional families the patients were carriers of metabolic anomalies potentially causing kidney stones&#46; In summary&#44; some sort of manifestation of hypercalciuria or urolithiasis occurred in 49 families &#40;73&#46;1&#37;&#41; of URA patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">We have previously reported a greater prevalence of hypercalciuria in pediatric patients with vesicoureteral reflux &#40;VUR&#41; than in the general population&#44; and hypothesized that urolithiasis in patients with VUR should have a metabolic origin&#46; We also reported that hypercalciuria was inherited as an autosomal dominant trait&#44; although with a higher probability of inheritance from the mother&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Recently&#44; Madani et al&#46; confirmed that the frequency of hypercalciuria was higher in pediatric patients with VUR than in healthy children&#44; although relatives were not studied&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The incidence of urolithiasis in patients with ureteropelvic junction obstruction &#40;UPJO&#41; is 16&#8211;44&#46;7&#37;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> with a 70-fold increased risk for developing kidney stones&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> In a previous survey&#44; Husmann et al&#46; reported that 76&#37; of patients with UPJO and simultaneous non-struvite renal calculi presented an identifiable metabolic abnormality&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> Hypercalciuria has been the most frequently reported metabolic disturbance in patients with UPJO<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">21&#44;22</span></a> although others&#44; such as hypocitraturia and hyperoxaluria&#44; have also been found&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> No mention is made of the origin of hypercalciuria and the other metabolic disturbances causing calculi present in patients with UPJO&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">We conducted a study to find out if children with UPJO have higher prevalence of hypercalciuria and whether their family members were affected by hypercalciuria and&#47;or urolithiasis&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> Hypercalciuria was found in 17&#47;27 children &#40;63&#37;&#41;&#44; 15 of them &#40;88&#37;&#41; had a familial history of urolithiasis&#46; Concerning the 10 children without hypercalciuria&#44; seven of them &#40;70&#37;&#41; had a familial history of urolithiasis&#46; Prevalence of both urolithiasis and hypercalciuria&#44; was not influenced by gender&#46; In summary&#44; in concordance with previous data&#44;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">21&#44;22</span></a> our results show that the prevalence of hypercalciuria is greater in pediatric patients with UPJO than in the general population and seems to be of genetic origin&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Subsequently&#44; we obtained results similar to those observed in the cases of VUR and UPJO in children diagnosed of simple renal cysts<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> and&#44; in neonatal renal pyelectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> Therefore&#44; these asymptomatic morphological anomalies &#40;renal cysts and&#44; neonatal renal pyelectasis&#41;&#44; while lacking clinical significance&#59; behave as other malformations potentially more harmful in terms of its association with genetic urolithiasis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Unilateral renal agenesis accounts for 5&#37; of CAKUT&#44; and it is defined as congenital absence of renal parenchymal tissue and arises from an error in organogenesis&#46; Multiple factors are thought to be implicated in the pathogenesis of renal agenesis including mutations in various genes important in renal development&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> The majority of patients are asymptomatic&#44; so it is usually diagnosed incidentally as a result of an antenatal ultrasound or as part of an evaluation for a urinary tract infection&#46; Unilateral renal agenesis can be accompanied by other CAKUT &#40;32&#37;&#41; and no renal anomalies&#46; Vesicoureteral reflux is the most common finding &#40;24&#37; of patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">As in other CAKUT anomalies&#44; in URA patients the formation of kidney stones has been observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">1&#44;2&#44;25</span></a> To our knowledge this is the first study that has studied metabolic disturbances causing calculi in children diagnosed with URA&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In our patients&#44; hypercalciuria frequency was 25&#46;4&#37;&#46; We previously reported the prevalence of hypercalciuria in control children in Tenerife island &#40;3&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> In other countries the hypercalciuria prevalence is reported between 0&#46;6&#37;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> and 12&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> Adding the patients with hypocitraturia&#44; the frequency of metabolic abnormalities causing of urolithiasis in URA patients rises to 38&#46;8&#37;&#46; We do not know of any hypocitraturia prevalence studies that have been performed in a control pediatric population&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The frequency of urolithiasis in first and second degree relatives of our patients &#40;62&#46;7&#37;&#41; was also higher than that which we have described in our community &#40;28&#46;1&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> The authors are aware that the use of a historical series of prevalence of urolithiasis&#44; although recent&#44; is a limitation of our study&#46; The prevalence of urolithiasis in the adult population is well studied in the medical literature&#44; but we not know of any studies where first and second degree relatives are studied simultaneously&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">It is also difficult to explain the reason why some patients were carriers of hypocitraturia and not of hypercalciuria&#46; In our experience we have seen that in many children with idiopathic hypercalciuria urinary calcium excretion can normalize around adolescence and&#44; at the same time&#44; reduce the citraturia&#46; Also&#44; we have observed&#44; in the families of some children with idiopathic hypercalciuria&#44; parents with urolithiasis had hypocitraturia and&#44; on the other hand&#44; a normal urinary calcium excretion&#46; It seems as if they were two sides of the same process&#46; It has been described that idiopathic hypercalciuria may be associated with hypocitraturia in absence of dRTA&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Longitudinal studies aimed at resolving this issue are required&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The renal malformation in which metabolic abnormalities has been most demonstrated to causes kidney stones is medullary sponge kidney &#40;Lenarduzzi&#8211;Cacchi&#8211;Ricci disease&#41;&#46; In this disorder&#44; the most common abnormality is idiopathic hypercalciuria &#40;88&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> In another study 65 of 97 patients &#40;67&#37;&#41; had at least one stone risk factor as hypercalciuria&#44; hypocitraturia&#44; hyperuricosuria or hyperoxaluria&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> Recently&#44; Fabris et al&#46; studied the families of 50 patients with medullary sponge kidney&#46; Twenty-seven probands &#40;54&#37;&#41; had 59 first- and second-degree relatives of both genders with medullary sponge kidney or urolithiasis&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> The authors concluded that their study provides strong evidence that familial clustering of medullary sponge kidney is common&#44; and has an autosomal dominant inheritance&#44; a reduced penetrance and variable expressivity&#46; The question is whether those family members have a milder form of medullary sponge kidney in some cases or simply kidney stones in the other&#44; something similar to what we have described in relatives of children with other CAKUT malformations&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The type of inheritance described by Fabris et al&#46; in the article previously mentioned<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> is similar to that which we have communicated in our patients with VUR<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> and UPJO&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> In summary&#44; and according to our hypothesis&#44; medullary sponge kidney would not be a renal disease <span class="elsevierStyleItalic">sensu stricto</span>&#44; but another renal malformation characterized by dilation of the collecting tubules which would share with other CAKUT anomalies &#40;RVU&#44; UPJO&#44; simple renal cysts&#44; URA&#41; a higher prevalence of hypercalciuria and&#47;or urolithiasis in the family members which is genetically transmitted to their descendants&#44; carriers of one or several among many possibilities of CAKUT development anomalies&#46; The hypothesis that medullary sponge kidney is a CAKUT malformation was suggested in two previous reports&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">32&#44;33</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Finally&#44; it is important to remember that idiopathic hypercalciuria has been described&#44; also in another kidney malformation&#58; the horseshoe kidney&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> It is also intriguing that in patients with an abnormality of glomerular development&#44; the thin basement membrane nephropathy&#44; has also been described with hypercalciuria&#44; hyperuricosuria and nephrolithiasis&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> Even thin basement membrane nephropathy can be associated with simple renal cysts&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">For many years in medical literature it could be read that the pathophysiologic mechanism of stone formation in children and adults with congenital urinary tract abnormalities were the urine stasis and infection&#46; The mechanisms are necessarily more complex&#46; We believe that the anomalies of the kidney development and genetic predisposition to produce kidney stones have a genetic connection that must be discovered in the next few years&#46; In genetic hypercalciuric stone-forming rats an increase has been reported in the number of receptors for vitamin D &#40;VDR&#41; both in the intestine and bone&#46; Favus et al&#46; showed in humans that peripheral monocytes of patients with idiopathic hypercalciuria have an increase in the number of vitamin D receptors&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> i&#46;e&#46; the same as the hypercalciuric rats&#46; Therefore&#44; an increase in the functional capacity of the complex calcitriol-VDR would be the most likely cause of idiopathic hypercalciuria&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Somehow vitamin D is involved in the kidney intrauterine development&#63; In 2001&#44; Wagner et al&#46; showed that the <span class="elsevierStyleItalic">WT1</span> gene product transcriptionally activates <span class="elsevierStyleItalic">VDR</span> expression in human embryonic kidney cells&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a><span class="elsevierStyleItalic">WT1</span> gene expression is critical for genitourinary development&#46; Homozygous disruption of this gen in mice caused agenesis of the kidneys&#44; likely as a result of a loss of metanephric blastemal cells&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a> In humans&#44; mutations in WT1 gene&#44; as well as Denys-Drash syndrome&#44; originates renal agenesis&#46; In their paper&#44; Wagner et al&#46; sounded a role for the vitamin D endocrine system in the regulation of renal cell growth and differentiation during development since up regulation of VDR by the WT1 transcription factor may mediate apoptosis of renal embryonic cells in response to 1&#44;25&#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> Is this Ariadne&#39;s thread that will help us to solve the labyrinth of the association between kidney stones and CAKUT anomalies&#63;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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    "tienePdf" => true
    "fechaRecibido" => "2015-06-04"
    "fechaAceptado" => "2015-09-07"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec749904"
          "palabras" => array:5 [
            0 => "Hypercalciuria"
            1 => "Hypocitraturia"
            2 => "Urolithiasis"
            3 => "Inheritance"
            4 => "Unilateral renal agenesis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec749903"
          "palabras" => array:5 [
            0 => "Hipercalciuria"
            1 => "Hipocitraturia"
            2 => "Urolitiasis"
            3 => "Herencia"
            4 => "Agenesia renal unilateral"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In few previous studies&#44; it has been reported that hypercalciuria is associated with some types of congenital anomalies of the kidney and urinary tract &#40;CAKUT&#41;&#44; namely ureteropelvic junction obstruction&#44; vesicoureteral reflux or simple renal cysts&#46; In addition&#44; one higher prevalence of hypercalciuria and&#47;or urolithiasis has been described in their family members compared to the general population&#46; This study was carried out to find out whether children with unilateral renal agenesis &#40;URA&#41; have these features previously described in other CAKUT types&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In a descriptive and multicenter study we studied the prevalence of hypercalciuria&#44; hypocitraturia and urolithiasis in 67 children &#40;43 males and 24 females&#41; with URA and their families&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The two metabolic anomalies that promote stone formation were observed in 26 children &#40;38&#46;8&#37;&#41;&#44; distributed as follows&#58; hypercalciuria in 16&#44; hypocitraturia in 9&#44; and both hypercalciuria and hypocitraturia in 1&#46; Eight children &#40;11&#46;9&#37;&#41; suffered renal colic during follow-up&#46; Familial history of urolithiasis was found in 42&#47;67 children &#40;62&#46;7&#37;&#41;&#58; in 12 of the first-degree relatives&#44; in 15 of the second degree relatives and in 15 patients both in the first-degree as in their second degree relatives&#46; In contrast&#44; in historic control group&#44; only in 28&#46;1&#37; of families at least one member had urolithiasis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our results show that the prevalence of hypercalciuria and&#47;or hypocitraturia is greater in pediatric patients with URA than in the general population&#46; Likewise&#44; the prevalence of urolithiasis in the families of these children is also higher than that in the general population&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">En escasos trabajos previos&#44; se ha comunicado que puede observarse la presencia de hipercalciuria en pacientes portadores de algunos tipos de CAKUT como estenosis pieloureteral&#44; reflujo vesicoureteral o quistes renales simples&#46; Adem&#225;s&#44; se ha descrito una prevalencia mayor de hipercalciuria y&#47;o urolitiasis en los miembros de las familias de esos ni&#241;os con algunos tipos de CAKUT&#44; en comparaci&#243;n con la poblaci&#243;n en general&#46; El presente estudio se llev&#243; a cabo para averiguar si los ni&#241;os con agenesia renal unilateral &#40;ARU&#41; tienen las caracter&#237;sticas descritas anteriormente en otros tipos de CAKUT&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En un estudio descriptivo y multic&#233;ntrico se determin&#243; la prevalencia de hipercalciuria&#44; hipocitraturia y urolitiasis en 67 ni&#241;os &#40;43 hombres y 24 mujeres&#41; con ARU y sus familias&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En 26 ni&#241;os &#40;38&#44;8&#37;&#41; se observaron las dos anomal&#237;as metab&#243;licas que favorecen la formaci&#243;n de c&#225;lculos renales distribuidos de la siguiente manera&#58; hipercalciuria en 16&#44; hipocitraturia en 9 y tanto hipercalciuria como hipocitraturia en 1&#46; Ocho ni&#241;os &#40;11&#44;9&#37;&#41; padecieron un c&#243;lico renal durante el tiempo total de seguimiento&#46; Una historia familiar de litiasis urinaria se encontr&#243; en 42&#47;67 de los ni&#241;os &#40;62&#44;7&#37;&#41;&#58; en familiares de primer grado en 12 de ellos&#44; en familiares de segundo grado en 15 y en ambos grados de familiares en los otros 15&#46; En contraste&#44; en el grupo de control hist&#243;rico&#44; solamente en 28&#44;1&#37; de las familias&#44; al menos&#44; un miembro hab&#237;a tenido urolitiasis&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestros resultados muestran que la prevalencia de la hipercalciuria y&#47;o hipocitraturia en pacientes pedi&#225;tricos con ARU es mayor que en la poblaci&#243;n general&#46; Asimismo&#44; la prevalencia de urolitiasis en las familias de estos ni&#241;os es tambi&#233;n mayor que en la poblaci&#243;n general&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Garcia Nieto V&#44; Huertes D&#237;az B&#44; Escribano Subias J&#44; Alarc&#243; Alacio MT&#44; Gonzalez Rodr&#237;guez JD&#44; Cabrera Sevilla JE&#44; et al&#46; Agenesia renal unilateral&#46; Nuevos argumentos acerca de la relaci&#243;n gen&#233;tica entre la urolitiasis y las malformaciones renales&#46; An Pediatr &#40;Barc&#41;&#46; 2016&#59;85&#58;240&#8211;246&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">All the children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Abnormal results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium&#47;creatinine ratio &#40;mg&#47;mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;12 &#40;0&#46;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#47;67 &#40;25&#46;4&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Citrate&#47;creatinine ratio &#40;mg&#47;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">670&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>354&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#47;56 &#40;17&#46;8&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&#47;creatinine ratio &#40;&#956;g&#47;&#956;mol&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;22 &#40;3&#46;26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;42 &#40;28&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maximum urine osmolality &#40;mOsm&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">941&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>142&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;64 &#40;10&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1233427.png"
              ]
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          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">A patient had hypercalciuria and hypocitraturia&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Metabolic and functional parameters&#46; Abnormal results&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Familial history of urolithiasis<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Hypercalciuria and&#47;or hypocitraturia</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="center" valign="top">Total</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1233428.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">In the first and&#47;or second generations&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Relationship between familial history of urolithiasis&#44; hypercalciuria and&#47;or hypocitraturia in the patients with URA&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Kidney developmental anomaly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hypercalciuria prevalence<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Prevalence of urolithiasis in first and second degree relatives<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vesicoureteral reflux&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ureteropelvic junction obstruction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Simple renal cysts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#37;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neonatal renal pyelectasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;7&#37;<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unilateral renal agenesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;4&#37;<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1233426.png"
              ]
            ]
          ]
          "notaPie" => array:5 [
            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Prevalence of hypercalciuria in healthy children in our island&#58; 3&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Prevalence of urolithiasis in first and second degree relatives in our island&#58; 28&#46;1&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>128&#41;&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Adding the children with hypocitraturia&#44; the prevalence of metabolic abnormalities causing of urolithiasis rises to 63&#46;6&#37;&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Adding the children with hypocitraturia&#44; the prevalence of metabolic abnormalities causing of urolithiasis rises to 30&#46;3&#37;&#46;</p>"
            ]
            4 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Adding the children with hypocitraturia&#44; the prevalence of metabolic abnormalities causing of urolithiasis rises to 38&#46;8&#37;&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Frequency of hypercalciuria in patients and urolithiasis in their relatives in the present report and in our reports carried out in children with four types of kidney development anomalies &#40;Refs&#46; <a class="elsevierStyleCrossRefs" href="#bib0230">8</a>&#41;&#46;</p>"
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Original Article
Unilateral renal agenesis. New arguments about the genetic relationship between kidney malformations and urolithiasis
Agenesia renal unilateral. Nuevos argumentos acerca de la relación genética entre la urolitiasis y las malformaciones renales
Victor Garcia Nietoa,
Corresponding author
vgarcianieto@gmail.com

Corresponding author.
, Beatriz Huertes Díazb, Joaquin Escribano Subiasc, Maria Teresa Alarcón Alaciod, Juan David Gonzalez Rodrígueze, José Eugenio Cabrera Sevillae, Carolina Peralta Arosf, Maria Isabel Luis Yanesa
a Pediatric Nephrology Section of the Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
b Hospital Universitario de Getafe, Madrid, Spain
c Hospital Universitari Sant Joan, Reus, Spain
d Hospital de Fuenlabrada, Madrid, Spain
e Hospital General Universitario Santa Lucía, Cartagena, Spain
f Hospital Uyapar, Puerto Ordaz, Venezuela
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            "entidad" => "Pediatric Nephrology Section of the Hospital Universitario Nuestra Se&#241;ora de Candelaria&#44; Santa Cruz de Tenerife&#44; Spain"
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    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Agenesia renal unilateral&#46; Nuevos argumentos acerca de la relaci&#243;n gen&#233;tica entre la urolitiasis y las malformaciones renales"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Association between urolithiasis and congenital anomalies of the kidney and urinary tract &#40;CAKUT&#41; has been described in children and adults since the 1920s&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> The cause of susceptibility to lithiasis was believed to be either&#58; urinary stasis&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> reduced urinary flow and urinary tract infection in which <span class="elsevierStyleItalic">Proteus</span> was the most common microorganism&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> Urinary stasis is generally assumed to play a major part in the pathogenesis of nephrolithiasis associated with distorted renal anatomy due to a delayed washout of crystals and risk of urinary infections&#46; The reported frequency of genitourinary anomalies in children with urolithiasis is between 19&#46;1&#37;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a> and 29&#46;8&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> However&#44; the exact pathogenic relationship between urolithiasis and CAKUT remains unclear&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We reported a higher incidence of hypercalciuria in children with vesicoureteral reflux &#40;VUR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> ureteropelvic junction obstruction<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> and simple renal cysts<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> in the general population&#44; and a higher positive family history of urolithiasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">6&#8211;8</span></a> This implies that children of parents with urolithiasis&#44; and&#47;or with a family history of urolithiasis&#44; would have increased susceptibility to have a kidney development abnormality&#46; These children also inherit hypercalciuria that could also favor formation of kidney stones&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The present study was conducted to find out if children with unilateral renal agenesis &#40;URA&#41; have a higher prevalence of hypercalciuria&#44; hypocitraturia and&#47;or a familiar history of urolithiasis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This descriptive and multicenter study included 67 children &#40;43 males&#44; 24 females&#41; with URA who were reviewed at Spanish Pediatric Nephrology Units of &#8220;Hospital Nuestra Se&#241;ora de Candelaria&#8221; &#40;Tenerife&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#41;&#44; &#8220;Hospital Universitari Sant Joan de Reus&#8221; &#40;Tarragona&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#44; &#8220;Hospital de Fuenlabrada&#8221; &#40;Madrid&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; and &#8220;Hospital General Universitario Santa Luc&#237;a&#8221; &#40;Cartagena&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46; The age at the time of the study was 10&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;84 years &#40;range&#58; 0&#46;16&#8211;21&#46;5&#41;&#46; The patients were controlled in each hospital from the postnatal ultrasound confirmation of the diagnosis of URA that had performed in utero&#44; i&#46;e&#46; since the first weeks of life&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">URA was located on the left side in 41 cases&#44; and on the right side in 26&#46; The diagnosis of URA was made by means of renal ultrasound and DMSA scan&#46; URA was associated with vesicoureteral reflux in three patients&#46; No other urinary tract malformations were found&#46; None of them had nephrocalcinosis or renal dysplasia morphological signs&#46; During follow-up&#44; 27 children suffered from urinary tract infections&#46; All patients were free of infection at the time of simple urine collection&#46; None of the patients were diagnosed with chronic renal failure&#46; None of the children showed elevated levels of plasma creatinine&#44; hypertension&#44; or signs of distal renal tubular acidosis&#46; We asked parents and&#47;or other relatives about family history of urolithiasis of the 67 children&#46; There was no background of consanguinity in the family histories&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The urine collected corresponded to non-fasting samples in which calcium&#44; citrate and creatinine were determined&#46; In accordance with criteria set by the <span class="elsevierStyleItalic">Spanish Paediatric Nephrology Association</span>&#44; hypercalciuria is diagnosed in children between 1 and 2 years of age when the calcium&#47;creatinine ratio &#40;UCa&#47;UCr&#41; from two individual&#44; consecutive measures is greater than 0&#46;47<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a> Based on the results of So et al&#46;&#44; hypercalciuria in children between 2 and 4 years of age was diagnosed when UCa&#47;UCr was greater than 0&#46;28<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> In children older than 4 years of age&#44; the diagnosis of hypercalciuria was made when the UCa&#47;UCr was greater than 0&#46;20<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> a value that corresponds to the 95th percentile of a sample made up of 100 healthy children&#44; from a previous study conducted by one of our groups&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> Based on Stapleton and Kroovand&#39;s criteria&#44; the hypocitraturia diagnosis criterion is a citrate&#47;creatinine ratio less than 400<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> In patients older than 14 years&#44; the hypocitraturia diagnosis criterion is a citrate&#47;creatinine ratio less than 250<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The UCa&#47;UCr ratio in non-fasting single spot urine was measured&#44; in addition&#44; to the parents of 29&#47;68 of the patients without changing their diets&#46; In these adults&#44; hypercalciuria was diagnosed when UCa&#47;UCr was higher than 0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#44; according to the average value previously found in our adult population from previous study conducted by one of our groups &#40;UCa&#47;UCr<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04<span class="elsevierStyleHsp" style=""></span>mg&#47;mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The results of urinary concentration test and urinary elimination of albumin were collected from the medical records&#46; The normal values used as reference to the maximum urine osmolality<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> and the albumin&#47;creatinine ratio<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> have been previously published&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The frequency of family history of urolithiasis in parents and other relatives of our URA patients was compared with a historical control group conducted in one of the hospitals participating in the study&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Analytical procedures and renal function tests</span><p id="par0050" class="elsevierStylePara elsevierViewall">In the laboratories of each of the hospitals participating in the study&#44; urinary creatinine was determined by the creatininase method&#44; calcium was measured by photometric assay&#44; urinary citrate was assessed by the citrate lyase method and urinary albumin was measured by a nephelometric technique &#40;Array&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Renal concentrating capacity was determined after administration of 20<span class="elsevierStyleHsp" style=""></span>&#956;g of desmopressin intranasal or 0&#46;12<span class="elsevierStyleHsp" style=""></span>mg &#40;120<span class="elsevierStyleHsp" style=""></span>&#956;g&#41; of oral desmopressin lyophilisate &#40;MELT&#41; that dissolves immediately in the mouth&#46; After emptying the bladder three urine samples were collected at 90<span class="elsevierStyleHsp" style=""></span>min intervals&#46; The highest osmolality value obtained was taken as the test result&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> Urinary osmolality was determined by measuring the freezing point depression in an Osmostat Osmometer &#40;Menarini&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical methods</span><p id="par0060" class="elsevierStylePara elsevierViewall">Kolmogorov&#8211;Smirnov test was used to study the distribution of the variables&#46; When they fit a normal distribution&#44; a notation of average value and standard deviation is used&#46; The other quantitative variables were expressed in terms of median and interquartile ranges&#46; Basic statistics were performed using SPSS statistical software &#40;SPSS V 19&#46;0&#44; SPSS Inc&#46;&#44; USA&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">All of the procedures and protocols followed during this study meet the ethical&#44; administrative&#44; and data protection requirements imposed by the Paediatrics Departments of the hospitals participants&#44; which are established in accordance with the law of Spain&#46; All parents gave informed consent&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Metabolic disorder was observed in 26 children&#58; hypercalciuria in 16 children &#40;11M&#44; 5F&#41;&#44; hypocitraturia in 9 cases &#40;5M&#44; 4F&#41; and both hypercalciuria and hypocitraturia in one patient&#46; Thereby we observed any risk of lithiasis in 38&#46;8&#37; of children with URA&#46; Eight children &#40;11&#46;9&#37;&#41; suffered renal colic during follow-up &#40;four with hypercalciuria and four with hypocitraturia&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the values of the studied parameters as well as the percentage of children with metabolic or functional anomalies&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The familial history of urolithiasis was found in 42&#47;67 children &#40;62&#46;7&#37;&#41;&#58; 12 in the first-degree&#44; 15 in the second degree and in 15 patients both in the first and second degree relatives&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Familial history of urolithiasis and the concomitant existence of hypercalciuria and&#47;or hypocitraturia in patients with URA were observed in 19 families&#46; In another 23 families only history of urolithiasis existed in children&#39;s relatives&#46; In another 7 families the patients were carriers of metabolic anomalies potentially causing kidney stones&#46; In 23 additional families&#44; only history of urolithiasis existed in children&#39;s relatives&#46; In 7 additional families the patients were carriers of metabolic anomalies potentially causing kidney stones&#46; In summary&#44; some sort of manifestation of hypercalciuria or urolithiasis occurred in 49 families &#40;73&#46;1&#37;&#41; of URA patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">We have previously reported a greater prevalence of hypercalciuria in pediatric patients with vesicoureteral reflux &#40;VUR&#41; than in the general population&#44; and hypothesized that urolithiasis in patients with VUR should have a metabolic origin&#46; We also reported that hypercalciuria was inherited as an autosomal dominant trait&#44; although with a higher probability of inheritance from the mother&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Recently&#44; Madani et al&#46; confirmed that the frequency of hypercalciuria was higher in pediatric patients with VUR than in healthy children&#44; although relatives were not studied&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The incidence of urolithiasis in patients with ureteropelvic junction obstruction &#40;UPJO&#41; is 16&#8211;44&#46;7&#37;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> with a 70-fold increased risk for developing kidney stones&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> In a previous survey&#44; Husmann et al&#46; reported that 76&#37; of patients with UPJO and simultaneous non-struvite renal calculi presented an identifiable metabolic abnormality&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> Hypercalciuria has been the most frequently reported metabolic disturbance in patients with UPJO<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">21&#44;22</span></a> although others&#44; such as hypocitraturia and hyperoxaluria&#44; have also been found&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> No mention is made of the origin of hypercalciuria and the other metabolic disturbances causing calculi present in patients with UPJO&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">We conducted a study to find out if children with UPJO have higher prevalence of hypercalciuria and whether their family members were affected by hypercalciuria and&#47;or urolithiasis&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> Hypercalciuria was found in 17&#47;27 children &#40;63&#37;&#41;&#44; 15 of them &#40;88&#37;&#41; had a familial history of urolithiasis&#46; Concerning the 10 children without hypercalciuria&#44; seven of them &#40;70&#37;&#41; had a familial history of urolithiasis&#46; Prevalence of both urolithiasis and hypercalciuria&#44; was not influenced by gender&#46; In summary&#44; in concordance with previous data&#44;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">21&#44;22</span></a> our results show that the prevalence of hypercalciuria is greater in pediatric patients with UPJO than in the general population and seems to be of genetic origin&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Subsequently&#44; we obtained results similar to those observed in the cases of VUR and UPJO in children diagnosed of simple renal cysts<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> and&#44; in neonatal renal pyelectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> Therefore&#44; these asymptomatic morphological anomalies &#40;renal cysts and&#44; neonatal renal pyelectasis&#41;&#44; while lacking clinical significance&#59; behave as other malformations potentially more harmful in terms of its association with genetic urolithiasis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Unilateral renal agenesis accounts for 5&#37; of CAKUT&#44; and it is defined as congenital absence of renal parenchymal tissue and arises from an error in organogenesis&#46; Multiple factors are thought to be implicated in the pathogenesis of renal agenesis including mutations in various genes important in renal development&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> The majority of patients are asymptomatic&#44; so it is usually diagnosed incidentally as a result of an antenatal ultrasound or as part of an evaluation for a urinary tract infection&#46; Unilateral renal agenesis can be accompanied by other CAKUT &#40;32&#37;&#41; and no renal anomalies&#46; Vesicoureteral reflux is the most common finding &#40;24&#37; of patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">As in other CAKUT anomalies&#44; in URA patients the formation of kidney stones has been observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">1&#44;2&#44;25</span></a> To our knowledge this is the first study that has studied metabolic disturbances causing calculi in children diagnosed with URA&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In our patients&#44; hypercalciuria frequency was 25&#46;4&#37;&#46; We previously reported the prevalence of hypercalciuria in control children in Tenerife island &#40;3&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> In other countries the hypercalciuria prevalence is reported between 0&#46;6&#37;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> and 12&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> Adding the patients with hypocitraturia&#44; the frequency of metabolic abnormalities causing of urolithiasis in URA patients rises to 38&#46;8&#37;&#46; We do not know of any hypocitraturia prevalence studies that have been performed in a control pediatric population&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The frequency of urolithiasis in first and second degree relatives of our patients &#40;62&#46;7&#37;&#41; was also higher than that which we have described in our community &#40;28&#46;1&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> The authors are aware that the use of a historical series of prevalence of urolithiasis&#44; although recent&#44; is a limitation of our study&#46; The prevalence of urolithiasis in the adult population is well studied in the medical literature&#44; but we not know of any studies where first and second degree relatives are studied simultaneously&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">It is also difficult to explain the reason why some patients were carriers of hypocitraturia and not of hypercalciuria&#46; In our experience we have seen that in many children with idiopathic hypercalciuria urinary calcium excretion can normalize around adolescence and&#44; at the same time&#44; reduce the citraturia&#46; Also&#44; we have observed&#44; in the families of some children with idiopathic hypercalciuria&#44; parents with urolithiasis had hypocitraturia and&#44; on the other hand&#44; a normal urinary calcium excretion&#46; It seems as if they were two sides of the same process&#46; It has been described that idiopathic hypercalciuria may be associated with hypocitraturia in absence of dRTA&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Longitudinal studies aimed at resolving this issue are required&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The renal malformation in which metabolic abnormalities has been most demonstrated to causes kidney stones is medullary sponge kidney &#40;Lenarduzzi&#8211;Cacchi&#8211;Ricci disease&#41;&#46; In this disorder&#44; the most common abnormality is idiopathic hypercalciuria &#40;88&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> In another study 65 of 97 patients &#40;67&#37;&#41; had at least one stone risk factor as hypercalciuria&#44; hypocitraturia&#44; hyperuricosuria or hyperoxaluria&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> Recently&#44; Fabris et al&#46; studied the families of 50 patients with medullary sponge kidney&#46; Twenty-seven probands &#40;54&#37;&#41; had 59 first- and second-degree relatives of both genders with medullary sponge kidney or urolithiasis&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> The authors concluded that their study provides strong evidence that familial clustering of medullary sponge kidney is common&#44; and has an autosomal dominant inheritance&#44; a reduced penetrance and variable expressivity&#46; The question is whether those family members have a milder form of medullary sponge kidney in some cases or simply kidney stones in the other&#44; something similar to what we have described in relatives of children with other CAKUT malformations&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The type of inheritance described by Fabris et al&#46; in the article previously mentioned<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> is similar to that which we have communicated in our patients with VUR<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> and UPJO&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> In summary&#44; and according to our hypothesis&#44; medullary sponge kidney would not be a renal disease <span class="elsevierStyleItalic">sensu stricto</span>&#44; but another renal malformation characterized by dilation of the collecting tubules which would share with other CAKUT anomalies &#40;RVU&#44; UPJO&#44; simple renal cysts&#44; URA&#41; a higher prevalence of hypercalciuria and&#47;or urolithiasis in the family members which is genetically transmitted to their descendants&#44; carriers of one or several among many possibilities of CAKUT development anomalies&#46; The hypothesis that medullary sponge kidney is a CAKUT malformation was suggested in two previous reports&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">32&#44;33</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Finally&#44; it is important to remember that idiopathic hypercalciuria has been described&#44; also in another kidney malformation&#58; the horseshoe kidney&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> It is also intriguing that in patients with an abnormality of glomerular development&#44; the thin basement membrane nephropathy&#44; has also been described with hypercalciuria&#44; hyperuricosuria and nephrolithiasis&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">35</span></a> Even thin basement membrane nephropathy can be associated with simple renal cysts&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">36</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">For many years in medical literature it could be read that the pathophysiologic mechanism of stone formation in children and adults with congenital urinary tract abnormalities were the urine stasis and infection&#46; The mechanisms are necessarily more complex&#46; We believe that the anomalies of the kidney development and genetic predisposition to produce kidney stones have a genetic connection that must be discovered in the next few years&#46; In genetic hypercalciuric stone-forming rats an increase has been reported in the number of receptors for vitamin D &#40;VDR&#41; both in the intestine and bone&#46; Favus et al&#46; showed in humans that peripheral monocytes of patients with idiopathic hypercalciuria have an increase in the number of vitamin D receptors&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> i&#46;e&#46; the same as the hypercalciuric rats&#46; Therefore&#44; an increase in the functional capacity of the complex calcitriol-VDR would be the most likely cause of idiopathic hypercalciuria&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Somehow vitamin D is involved in the kidney intrauterine development&#63; In 2001&#44; Wagner et al&#46; showed that the <span class="elsevierStyleItalic">WT1</span> gene product transcriptionally activates <span class="elsevierStyleItalic">VDR</span> expression in human embryonic kidney cells&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a><span class="elsevierStyleItalic">WT1</span> gene expression is critical for genitourinary development&#46; Homozygous disruption of this gen in mice caused agenesis of the kidneys&#44; likely as a result of a loss of metanephric blastemal cells&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a> In humans&#44; mutations in WT1 gene&#44; as well as Denys-Drash syndrome&#44; originates renal agenesis&#46; In their paper&#44; Wagner et al&#46; sounded a role for the vitamin D endocrine system in the regulation of renal cell growth and differentiation during development since up regulation of VDR by the WT1 transcription factor may mediate apoptosis of renal embryonic cells in response to 1&#44;25&#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> Is this Ariadne&#39;s thread that will help us to solve the labyrinth of the association between kidney stones and CAKUT anomalies&#63;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "identificador" => "xres746734"
          "titulo" => "Abstract"
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              "titulo" => "Background"
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          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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              "identificador" => "abst0025"
              "titulo" => "Antecedentes"
            ]
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              "titulo" => "M&#233;todos"
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          "titulo" => "Palabras clave"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "titulo" => "Subjects and methods"
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            0 => array:2 [
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              "titulo" => "Patients"
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              "identificador" => "sec0025"
              "titulo" => "Analytical procedures and renal function tests"
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              "titulo" => "Statistical methods"
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          "titulo" => "Results"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2015-06-04"
    "fechaAceptado" => "2015-09-07"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec749904"
          "palabras" => array:5 [
            0 => "Hypercalciuria"
            1 => "Hypocitraturia"
            2 => "Urolithiasis"
            3 => "Inheritance"
            4 => "Unilateral renal agenesis"
          ]
        ]
      ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec749903"
          "palabras" => array:5 [
            0 => "Hipercalciuria"
            1 => "Hipocitraturia"
            2 => "Urolitiasis"
            3 => "Herencia"
            4 => "Agenesia renal unilateral"
          ]
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      ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In few previous studies&#44; it has been reported that hypercalciuria is associated with some types of congenital anomalies of the kidney and urinary tract &#40;CAKUT&#41;&#44; namely ureteropelvic junction obstruction&#44; vesicoureteral reflux or simple renal cysts&#46; In addition&#44; one higher prevalence of hypercalciuria and&#47;or urolithiasis has been described in their family members compared to the general population&#46; This study was carried out to find out whether children with unilateral renal agenesis &#40;URA&#41; have these features previously described in other CAKUT types&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In a descriptive and multicenter study we studied the prevalence of hypercalciuria&#44; hypocitraturia and urolithiasis in 67 children &#40;43 males and 24 females&#41; with URA and their families&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The two metabolic anomalies that promote stone formation were observed in 26 children &#40;38&#46;8&#37;&#41;&#44; distributed as follows&#58; hypercalciuria in 16&#44; hypocitraturia in 9&#44; and both hypercalciuria and hypocitraturia in 1&#46; Eight children &#40;11&#46;9&#37;&#41; suffered renal colic during follow-up&#46; Familial history of urolithiasis was found in 42&#47;67 children &#40;62&#46;7&#37;&#41;&#58; in 12 of the first-degree relatives&#44; in 15 of the second degree relatives and in 15 patients both in the first-degree as in their second degree relatives&#46; In contrast&#44; in historic control group&#44; only in 28&#46;1&#37; of families at least one member had urolithiasis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our results show that the prevalence of hypercalciuria and&#47;or hypocitraturia is greater in pediatric patients with URA than in the general population&#46; Likewise&#44; the prevalence of urolithiasis in the families of these children is also higher than that in the general population&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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            "titulo" => "Conclusion"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">En escasos trabajos previos&#44; se ha comunicado que puede observarse la presencia de hipercalciuria en pacientes portadores de algunos tipos de CAKUT como estenosis pieloureteral&#44; reflujo vesicoureteral o quistes renales simples&#46; Adem&#225;s&#44; se ha descrito una prevalencia mayor de hipercalciuria y&#47;o urolitiasis en los miembros de las familias de esos ni&#241;os con algunos tipos de CAKUT&#44; en comparaci&#243;n con la poblaci&#243;n en general&#46; El presente estudio se llev&#243; a cabo para averiguar si los ni&#241;os con agenesia renal unilateral &#40;ARU&#41; tienen las caracter&#237;sticas descritas anteriormente en otros tipos de CAKUT&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En un estudio descriptivo y multic&#233;ntrico se determin&#243; la prevalencia de hipercalciuria&#44; hipocitraturia y urolitiasis en 67 ni&#241;os &#40;43 hombres y 24 mujeres&#41; con ARU y sus familias&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En 26 ni&#241;os &#40;38&#44;8&#37;&#41; se observaron las dos anomal&#237;as metab&#243;licas que favorecen la formaci&#243;n de c&#225;lculos renales distribuidos de la siguiente manera&#58; hipercalciuria en 16&#44; hipocitraturia en 9 y tanto hipercalciuria como hipocitraturia en 1&#46; Ocho ni&#241;os &#40;11&#44;9&#37;&#41; padecieron un c&#243;lico renal durante el tiempo total de seguimiento&#46; Una historia familiar de litiasis urinaria se encontr&#243; en 42&#47;67 de los ni&#241;os &#40;62&#44;7&#37;&#41;&#58; en familiares de primer grado en 12 de ellos&#44; en familiares de segundo grado en 15 y en ambos grados de familiares en los otros 15&#46; En contraste&#44; en el grupo de control hist&#243;rico&#44; solamente en 28&#44;1&#37; de las familias&#44; al menos&#44; un miembro hab&#237;a tenido urolitiasis&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestros resultados muestran que la prevalencia de la hipercalciuria y&#47;o hipocitraturia en pacientes pedi&#225;tricos con ARU es mayor que en la poblaci&#243;n general&#46; Asimismo&#44; la prevalencia de urolitiasis en las familias de estos ni&#241;os es tambi&#233;n mayor que en la poblaci&#243;n general&#46;</p></span>"
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            "titulo" => "M&#233;todos"
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            "titulo" => "Resultados"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Garcia Nieto V&#44; Huertes D&#237;az B&#44; Escribano Subias J&#44; Alarc&#243; Alacio MT&#44; Gonzalez Rodr&#237;guez JD&#44; Cabrera Sevilla JE&#44; et al&#46; Agenesia renal unilateral&#46; Nuevos argumentos acerca de la relaci&#243;n gen&#233;tica entre la urolitiasis y las malformaciones renales&#46; An Pediatr &#40;Barc&#41;&#46; 2016&#59;85&#58;240&#8211;246&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">All the children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Abnormal results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium&#47;creatinine ratio &#40;mg&#47;mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;12 &#40;0&#46;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#47;67 &#40;25&#46;4&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Citrate&#47;creatinine ratio &#40;mg&#47;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">670&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>354&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#47;56 &#40;17&#46;8&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&#47;creatinine ratio &#40;&#956;g&#47;&#956;mol&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;22 &#40;3&#46;26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#47;42 &#40;28&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maximum urine osmolality &#40;mOsm&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">941&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>142&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;64 &#40;10&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">A patient had hypercalciuria and hypocitraturia&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Metabolic and functional parameters&#46; Abnormal results&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Familial history of urolithiasis<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Hypercalciuria and&#47;or hypocitraturia</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="center" valign="top">Total</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Frequency of hypercalciuria in patients and urolithiasis in their relatives in the present report and in our reports carried out in children with four types of kidney development anomalies &#40;Refs&#46; <a class="elsevierStyleCrossRefs" href="#bib0230">8</a>&#41;&#46;</p>"
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                            0 => "N&#46;P&#46; So"
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