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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">UTI is by far the most common infection after kidney transplantation &#40;KTX&#41;&#46; Its incidence is highly variable&#44; ranging between 23 and 75&#37; in the first year&#46; This wide variability may be due to different screening strategies&#44; definitions&#44; population characteristics&#44; and prophylactic strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> It increases the morbidity and mortality in kidney allograft recipients&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">2&#8211;4</span></a> On the other hand&#44; antibiotic treatment and prophylaxis for UTI increase antibiotic resistance as well as <span class="elsevierStyleItalic">Clostridioides difficile</span> infection&#46; Therefore&#44; searching for prevention strategies aimed at limiting antibiotic use and reducing the UTI incidence should be pursued&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although non-antimicrobial therapies have already proven some benefit in clinical trials in general population&#44; there is few evidence in SOT&#46; Methenamine&#44; probiotics and bacterial vaccines are well tolerated&#44; but data are drawn from small case series and non-randomized clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">5&#8211;7</span></a> The role of cranberry juice is still controversial&#58; even though several studies suggest it is useful for kidney transplants with recurrent UTI&#44; a recent Cochrane systematic review and meta-analysis found that&#44; compared with placebo&#44; cranberry juice did not significantly reduce the incidence of UTI&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSmallCaps">d</span>-Mannose&#44; a simple sugar&#44; could play a role in the prevention of UTI by inhibiting the attachment of bacterial type 1 fimbriae to the urothelium&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> In vitro data suggest that Proanthocyanidins &#40;PAC&#41; inhibits the adherence of <span class="elsevierStyleItalic">Escherichia coli</span> by a similar mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a> Studies in murine models of UTI with different mannoside fimbriae antagonist led to a reduction in the number of UFC&#47;ml in the urine&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> Both <span class="elsevierStyleSmallCaps">d</span>-Mannose and PAC have also shown promising results in reducing the risk of recurrent UTI in healthy women&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> but their effect on UTI infection after kidney transplantation has not been evaluated yet&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The purpose of this clinical trial is to test the efficacy and safety of a 24-h prolonged release formulation of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC vs&#46; PAC alone&#44; administered on UTI and&#47;or AB episodes throughout the first 3 months after kidney transplantation&#44; pursuit by a follow-up period of 3 months&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">This is a pilot&#44; randomized&#44; double-blind parallel study group &#40;1&#58;1 ratio&#41; clinical trial&#44; comparing the efficacy of daily intake of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC vs&#46; PAC alone to prevent UTI and AB after kidney transplantation&#46; Since the mechanism of the mannose in experimental models has led to a reduction in CFU&#47;ml in urine&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> we decided to screen for asymptomatic bacteriuria throughout the study to detect if its addition to PAC reduces the bacterial colonization and&#47;or its correlation with UTI&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">UC were screen with the following frequency&#58; once a week after the first month of KTX&#44; twice a month until the 3rd month and once a month until the 6th month post-transplant&#59; also&#44; at each time that the patient experiences any urinary symptom&#46; AB was treated just in the first 3 weeks after transplantation&#46; A TMP&#47;SMX prophylaxis was given following the local protocol during the first 3 months after transplantation&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">During an episode of UTI or AB that required antibiotic treatment&#44; patients were educated to continue study supplements intake&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the study protocol&#46; This clinical trial was registered on clinicaltrials&#46;gov &#40;<a href="ctgov:NCT05109455">NCT05109455</a>&#41; and sponsored by Arafarma S&#46;A&#46; Entry of data into the study database and analysis of the results were done independently by academic authors without the involvement of the sponsor&#46; Since both formulations are dietary supplements and the dosage used was proven to be safe&#44; the study was considered as a low-intervention clinical trial by the Spanish Regulatory Agency &#40;AEMPS&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The internal ethical review board of our institution approved the trial &#40;PR421&#47;18&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Medication</span><p id="par0045" class="elsevierStylePara elsevierViewall">The product is a supplement consisting of <span class="elsevierStyleSmallCaps">d</span>-Mannose&#44; PAC and Ursodeoxycholic acid&#44; as well as several vitamins&#46; Supplements were provided by the Sponsor of the study&#46; See <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 1</a> for more information about the composition&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Population</span><p id="par0050" class="elsevierStylePara elsevierViewall">Eligible patients were those who had received a kidney transplant at Bellvitge University Hospital between April 2019 and September 2020&#46; Exclusion criteria were&#58; age below 18 years&#44; recipients of an organ transplant other than kidney&#44; patients with Bricker or Studer neobladders&#44; and those participating in another clinical study in which the sponsor had already established the treatment for UTI or whose immunosuppressive protocols differed from our local practice&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Definitions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Asymptomatic bacteriuria was defined as a culture yielding significant growth of urinary tract pathogens &#40;&#62;10<span class="elsevierStyleSup">5</span><span class="elsevierStyleHsp" style=""></span>colony forming units&#47;ml&#41; in the absence of symptoms attributable to the infection&#46; UTI was defined as the presence of a positive urine culture &#40;bacteriuria count<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">5</span><span class="elsevierStyleHsp" style=""></span>colony forming units&#47;ml&#41; in the presence of urinary symptoms&#46; The type of UTI was defined according to the international guidelines<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a>&#58; Episodes of urinary frequency augmentation&#44; dysuria&#44; or suprapubic pain without fever were categorized as cystitis&#46; Patients having fever and a positive culture as defined above&#44; with or without flank pain&#44; were diagnosed as having acute graft pyelonephritis &#40;AGP&#41;&#46; Acute bacterial Prostatitis was defined as the presence of discomfort referred to the lower urogenital and perineal area associated to fever and chills&#46; Recurrent UTI was defined as the occurrence of at least two episodes of UTI within 6 months&#46; Contaminated cultures&#44; considered as those where more than 2 microorganisms were isolated from a single specimen with less than 10<span class="elsevierStyleSup">5</span><span class="elsevierStyleHsp" style=""></span>colony forming units&#47;ml without symptoms&#44; were excluded from the study analysis&#46; A multi-resistant bacterium is one that exhibits resistance to a minimum of 3 antibiotic groups or to a specific group of antibiotics &#40;extended-spectrum beta-lactamases&#44; methicillin-resistant Staphylococcus aureus&#44; and carbapenemases&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">More details on microbiological technique analytics&#44; and ureteric stent manipulation are depicted in <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Box 1</a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Outcomes</span><p id="par0065" class="elsevierStylePara elsevierViewall">The primary outcome was a composite endpoint of the incidence &#40;first episode&#41; of UTI and&#47;or AB within the first 6 months after kidney transplantation&#46; For analysis purpose&#44; we showed outcomes also according to 3 time periods&#58; period 1&#44; from first day after kidney transplantation to double J removal &#40;21&#8211;27 days post-transplantation&#41;&#59; period 2&#44; from double J removal to the last day of supplements intake &#40;meaning 3 months after KTX&#41;&#59; and period 3&#44; from the third month to the end of study follow-up &#40;6 months&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The secondary outcomes were&#58; global incidence of UTI and&#47;or AB&#44; analysis of types of UTIs&#44; microbiological characteristics&#44; incidence of double J colonization&#44; incidence of delayed graft function &#40;DGF&#41;&#44; rejection rates&#44; kidney allograft function&#44; incidence and type of adverse events&#44; and patient and kidney survival&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We followed the Consort 2010 checklist &#40;Consolidated Standards of Reporting Trials&#41; in reporting the results of this trial&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Randomization and medication administration</span><p id="par0080" class="elsevierStylePara elsevierViewall">After randomization&#44; patients received the first dose of either Mannose plus PAC or PAC alone within the first 24<span class="elsevierStyleHsp" style=""></span>h from transplantation&#46; In case of paralytic ileus&#44; the introduction of study product or of the comparator could be delayed until 72<span class="elsevierStyleHsp" style=""></span>h&#46; After this time&#44; as well as in case of immediate transplant removal due to thrombosis&#44; patients were considered screening failure&#46; The study was double-blinded&#46; For more details on the protocol&#44; see <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Fig&#46; 1 and Supplementary Box 2</a>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Statistics</span><p id="par0085" class="elsevierStylePara elsevierViewall">This is a pilot and exploratory trial&#44; and a sample-size was estimated&#46; Continuous variables were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; or median and interquartile range &#40;IQR&#41;&#44; and categorical variables as number of total &#40;<span class="elsevierStyleItalic">n</span>&#41; and percentage &#40;&#37;&#41;&#46; Comparison between groups was performed using Pearson&#8217; <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test for categorical data&#44; and the Fisher-exact test was applied when the number of cases was less than five&#46; One-way analysis of variance and <span class="elsevierStyleItalic">t</span>-tests were used for normally continuous distributed data&#44; and nonparametric Kruskal&#8211;Wallis test and Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span>-test for non-normally distributed variables&#46; Free survival from UTI was analyzed through Kaplan&#8211;Meier analysis&#46; All <span class="elsevierStyleItalic">p</span>-values were two-tailed and statistical significance level was fixed at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; SPSS 20&#46;0 software &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#41; and GraphPad Prism version 6&#46;0 &#40;GraphPad Software&#44; La Jolla&#44; CA&#41; were used for data management and analysis&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">Between April 2019 and September 2020&#44; 140 kidney transplants were performed at our center&#46; Ten patients did not meet the study inclusion criteria&#44; seven patients were not willing to participate&#44; and 63 patients already participated in other clinical studies&#46; Overall&#44; 60 patients were included in the study and randomized in two groups&#58; a control group &#40;PAC alone&#41;&#44; and an experimental group using Mannose plus PAC&#46; Three patients dropped out from each group&#46; In the experimental group&#44; two patients dropped out due to study protocol deviations &#40;taking treatment during only the first week after transplantation&#44; then withdrawing their consent to stay in the study&#41;&#44; and a third one died after COVID-19 infection&#46; In the control group&#44; one patient requested to drop out of the study&#59; one patient had a never-functioning graft&#59; and one patient died after COVID-19 infection&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the flowchart of the study&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; no statistically significant differences were observed between the two treatment groups regarding the baseline characteristics&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Study outcomes</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">UTI and AB</span><p id="par0100" class="elsevierStylePara elsevierViewall">There were 94 UTI and AB episodes in the whole cohort &#40;3&#46;4 UTI and AB episodes for patient&#47;year &#8211; see <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 2</a>&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes the results&#44; showing no differences in the outcomes per study group&#46; 31 patients had at least one episode of AB&#44; 17 &#40;63&#37;&#41; in the Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC group vs&#46; 14 &#40;52&#37;&#41; in the control group &#40;<span class="elsevierStyleItalic">p</span> 0&#46;4&#41;&#59; six had cystitis&#44; 2 &#40;7&#37;&#41; vs&#46; 4 &#40;14&#37;&#41; <span class="elsevierStyleItalic">p</span> 0&#46;3&#44; and nine had acute pyelonephritis 4 &#40;14&#37;&#41; vs&#46; 5 &#40;18&#37;&#41; <span class="elsevierStyleItalic">p</span> 0&#46;5&#46; Six pyelonephritis episodes appeared after urinary manipulation &#40;two episodes occurred after the double J ureteral stent removal&#44; three episodes after the bladder stent removal&#44; and one after nephrostomy placement&#41;&#46; Two patients had recurrent UTI &#40;one for each group&#41;&#46; Also&#44; the total number of UTI and AB episodes was similar among groups &#40;3&#46;1 UTI and AB&#47;patient&#47;year vs&#46; 3&#46;9 UTI and AB&#47;patient&#47;year for experimental vs&#46; control group respectively&#44; <span class="elsevierStyleItalic">p</span> 0&#46;7&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">We analyzed UTI and AB episodes and incidence according to three different periods &#40;see <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; and&#44; again&#44; we did not observe significant differences between the two groups&#46; Also&#44; when comparing groups after removal of double J&#44; we did not observe differences in patients having at least one UTI and AB episode &#40;49&#37; Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC vs&#46; 59&#37; PAC alone&#44; <span class="elsevierStyleItalic">p</span> 0&#46;41&#41;&#46; As expected&#44; UTIs were more frequent in the first three months &#40;periods 1 and 2&#41; compared with the following three month-period &#40;median UTI episodes 1 &#91;0&#8211;5&#93; vs&#46; 0 &#91;0&#8211;3&#93;&#44; <span class="elsevierStyleItalic">p</span> 0&#46;002&#41; in the whole cohort&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Median time to first UTI and AB episode was similar in both study groups &#40;14 IQ 6&#8211;23 days vs&#46; 22 IQ 7&#8211;29 days&#44; <span class="elsevierStyleItalic">p</span> 0&#46;3&#41;&#46; Also&#44; the time of the first occurrence of UTI and&#47;or AB was similar &#40;log Rank <span class="elsevierStyleItalic">p</span> 0&#46;4 see <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Fig&#46; 2</a>&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Patients with urological complications had a higher UTI and AB incidence &#40;83&#37; vs&#46; 50&#37;&#44; <span class="elsevierStyleItalic">p</span> 0&#46;034&#41;&#46; Correlation with AB and pyelonephritis was statistically significant &#40;<span class="elsevierStyleItalic">r</span> 0&#46;3&#44; <span class="elsevierStyleItalic">p</span> 0&#46;02&#41;&#46; In 5 patients&#44; pyelonephritis was caused by the same bacteria as previously identified in an AB culture&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Females tended to have a higher UTI incidence&#44; although this was statistically significant only for asymptomatic bacteriuria &#40;72&#37; vs&#46; 44&#37; for female vs&#46; male patients&#44; <span class="elsevierStyleItalic">p</span> 0&#46;04&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">No differences in frequency of isolated bacteria culture type were observed among study groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Of note&#44; we did not observe significant differences regarding UTI and AB due to <span class="elsevierStyleItalic">E&#46; coli</span> between groups&#44; neither when excluding the period prior to the double J removal &#40;24&#37; vs&#46; 17&#37; for Mannose plus PAC vs&#46; PAC alone respectively&#44; <span class="elsevierStyleItalic">p</span> 0&#46;2&#41;&#46; <span class="elsevierStyleItalic">E&#46; coli</span> was the most frequent pathogen&#44; observed in 28&#37; of UTI and AB episodes&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Multidrug-resistant microorganism UTI and&#47;or BA episodes were detected in 7 of 17 patients in the Mannose plus PAC group as opposed to 4 of 16 patients in the PAC alone group &#40;41&#37; vs&#46; 27&#37;&#44; <span class="elsevierStyleItalic">p</span> 0&#46;472&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding the length of antibiotics course&#44; there was no statistical significant difference &#40;median 7 IQ 1&#8211;14 vs&#46; 12 days IQ 1&#8211;15&#44; for Mannose plus PAC vs&#46; PAC alone&#44; <span class="elsevierStyleItalic">p</span> 0&#46;44&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The frequency of uropathogens isolated in the whole cohort is showed in <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Fig&#46; 3</a>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Kidney transplant-related outcomes</span><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> shows the main graft and urological-related outcomes depending on treatment group&#46; No major differences were observed&#46; 26&#37; of patients in the experimental group and 22&#37; of patients in the control group had DGF&#46; One patient from each group developed an acute allograft rejection&#46; The eGFR at 6 months post-transplantation was also similar&#46; There was 1 episode of lithiasis in each group&#44; in both cases kidney stones were transferred from the donor&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Double J cultures</span><p id="par0150" class="elsevierStylePara elsevierViewall">All double J catheters except one were cultured&#44; the one exception being due to accidental contamination during the removal procedure&#46; Out of the 53 cultured catheters&#44; 40&#37; were colonized&#58; 13&#37; had typical uropathogens&#44; 22&#37; had non-uropathogens&#44; and 4&#37; had both type of bacteria&#46; Colonization of double J was similar between groups &#40;48&#37; vs&#46; 31&#37; for Mannose plus PAC vs&#46; PAC alone&#44; <span class="elsevierStyleItalic">p</span> 0&#46;19&#41;&#46; The presence of uropathogens in double J culture was higher in patients with UTIs &#40;89&#37; vs&#46; 55&#37;&#44; <span class="elsevierStyleItalic">p</span> 0&#46;04&#41; and in patients with asymptomatic bacteriuria &#40;89 vs&#46; 51&#37;&#44; <span class="elsevierStyleItalic">p</span> 0&#46;03&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Safety</span><p id="par0155" class="elsevierStylePara elsevierViewall">The adverse effects reported were minor&#46; In total&#44; 50&#37; of patients presented adverse effects&#59; being 51&#46;9&#37; in those treated with PAC alone and 48&#46;1&#37; in those treated with Mannose &#40;<span class="elsevierStyleItalic">p</span> 0&#46;7&#41;&#46; Diarrhea was the most frequently reported adverse event in both groups &#40;see <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">The present study explores the feasibility of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC use in preventing UTI after kidney transplantation&#46; The main finding is it does not reduce UTI incidence in the first three months after kidney transplantation compared with PAC alone&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The rationale for the combination is the potentially synergic effect&#46; <span class="elsevierStyleSmallCaps">d</span>-Mannose avoids the infection by targeting a specific type of fimbriae&#58; The FimH or the mannose-sensitive &#40;type 1&#41;&#44; whereas PAC contains other lectin-mediated inhibitor that targets the Fim P which are mannose resistant&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">A combination of non-antibiotic measures might lead to superior results to monotherapy&#44; as shown in a small pilot study in 33 premenopausal women&#59; with a combination of <span class="elsevierStyleSmallCaps">d</span>-Mannose with cranberry extract and lactobacilli&#59; to successfully treat acute uncomplicated cystitis and symptoms of UTI&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Vasileiou et al&#46; suggested that other cranberry components such as ursolic acid&#44; have a synergistic role with PAC in the antiad-hesion process by causing differential gene expression in <span class="elsevierStyleItalic">E&#46; coli</span>&#44; resulting in inhibition of biofilm formation&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a> That&#39;s why it was added to the treatment powder in the experimental group as shown in <a class="elsevierStyleCrossRef" href="#sec0105">Supplementary Table 1</a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Some studies in general population suggest that non-antibiotic prevention strategies are useful&#46; There is one multicenter-randomized trial from Spain including 93 non-transplant women with recurrent non-complicated UTI&#44; randomized to receive Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC vs&#46; PAC&#44; and&#44; in contrast with our results&#44; the percentage of UTI in the group treated with Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC was 24&#37;&#44; vs&#46; 45&#37; in the PAC group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> More recently&#44; Lenger et all found&#44; in a meta-analysis comparing <span class="elsevierStyleSmallCaps">d</span>-Mannose vs&#46; other agents for recurrent UTI prevention in adult women&#44; that <span class="elsevierStyleSmallCaps">d</span>-Mannose appears to be as effective as antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">In the pathogenesis of UTIs&#44; not only the attachment of uropathogens to the urothelium is important&#44; but also their ability to produce biofilm&#59; composed of bacteria and self-produced mucopolysaccharides&#46; Biofilm can be formed at the surface of any inert structure such as catheters&#46; Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC acts by preventing bacterial adhesion&#44; but their efficacy against the biofilm is probably limited&#46; Therefore&#44; the negative results from our study could be explained by the biofilm persistence &#40;present&#44; for example&#44; in double J catheters&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> To support this hypothesis&#44; our study analyzed&#44; by a special sonication technique&#44; the presence of biofilm at the ureteral &#40;double J&#41; catheter and found that the uropathogens attached to the stent are common &#40;40&#37; were colonized 13&#37; of them with typical uropathogens&#41; and found that the presence of uropathogens in double J culture was higher in patients with UTIs &#40;89&#37; Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC vs&#46; 55&#37; PAC alone&#44; <span class="elsevierStyleItalic">p</span> 0&#46;04&#41; and in patients with asymptomatic bacteriuria &#40;89 vs&#46; 51&#37;&#44; <span class="elsevierStyleItalic">p</span> 0&#46;03&#41; respectively&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">AB remains a controversial issue in kidney transplantation&#59; while there is consensus to avoid the screening after two months post-surgery&#59; guidelines still consider evaluating the short course of antibiotic if AB is detected in the first months after kidney transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> The low number of cystitis reported in our study and the high number of AB are probably due to inconsistency of symptoms &#40;especially dysuria&#41; that could be often underreported or related to double J catheter irritation&#46; This could also explain the low rate of UTI recurrence in our study&#46; Moreover&#44; although AB is not considered UTI&#44; in the first days after transplantation&#44; when a vesical catheter or a double J is inserted&#44; the impact of AB is unknown&#46; In our study&#44; 55&#37; of pyelonephritis was anticipated by AB&#44; sharing the same bacteria previously detected in the screening cultures&#59; thus&#44; suggesting that&#44; at least at an initial phase&#44; screening for AB could be useful&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">In terms of tolerance&#44; the reported adverse events were minor and mainly gastrointestinal &#40;GI&#41;&#46; Therefore&#44; the addition of Mannose was not associated with a higher number of adverse events&#46; However&#44; our numbers are higher than those reported by Casado et al&#46; in their study in non-transplanted women&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> Indeed&#44; in transplant population GI-adverse events are very common&#44; occurring in up to 20&#37; of patients&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a> especially in those treated with MPA&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">21</span></a> as recently showed in the TRANSFORM study&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a> Thus&#44; the reported adverse events seem to be related to the kidney transplant procedure and to the immunosuppressants&#44; rather than associated with the study medication&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The present study has some limitations&#46; Due to its exploratory design&#44; the statistical power is limited by the small number of patients included and by a low number of UTI compared to AB&#46; Also&#44; the follow-up period is quite short&#44; nonetheless most UTIs in kidney transplant recipients occur early after surgery and their incidence decreases with time&#46; Finally&#44; although the lack of a comparator group with placebo is another limitation&#44; our study was designed to provide evidence that the synergist effect of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC could be capable to reduce incidence of UTI or AB rather than PAC alone&#46; On the other hand&#44; our study has some strengths&#44; such as the design of the clinical trial &#40;randomized&#44; double-blind&#44; prospective&#41;&#44; the high number of microbiological culture and the precise technique used to analyze the double J&#46; For all these reason we believe that the negative result of our feasibility study recommends avoiding designing larger studies with <span class="elsevierStyleSmallCaps">d</span>-Mannose or PAC in KT&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conclusions</span><p id="par0205" class="elsevierStylePara elsevierViewall">With the present study&#44; we have provided valuable information on a prophylactic strategy that has proven to be effective in non-transplanted population&#46; Unfortunately&#44; the use of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC in the early post-transplant period&#44; even though safe and well tolerated&#44; does not seem to add any protective effect&#44; confirming once again the complexity of pathogenesis in the kidney transplant population and the unmet need for preventive strategies for UTI&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Author&#39;s contributions</span><p id="par0210" class="elsevierStylePara elsevierViewall">M&#46;R&#46;&#44; E&#46;M&#46;&#44; A&#46;S&#46;&#44; J&#46;C&#46; helped recruiting data&#44; prepared the draft and performed the statistical analysis of the study&#46; N&#46;S&#46;&#44; S&#46;M&#46;&#44; A&#46;C&#46;&#44; C&#46;A&#46; helped with the microbiological analysis of the catheters&#46; M&#46;F&#46;&#44; L&#46;R&#46;&#44; B&#46;E&#46; helped with the catheter&#39;s extraction and correct transportation&#46; M&#46;D&#46; performed the follow-up and support to any patients concerned&#46; All authors critically reviewed and approved the manuscript draft&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Funding</span><p id="par0215" class="elsevierStylePara elsevierViewall">This study was supported by <span class="elsevierStyleGrantSponsor" id="gs1">Instituto de Salud Carlos III &#40;ISCIII&#41;</span>&#44; RICORS 2040 <span class="elsevierStyleGrantNumber" refid="gs1">RD21&#47;0005&#47;0021</span>&#46; Financed by the <span class="elsevierStyleGrantSponsor" id="gs2">&#8220;European Union &#8211; NextGenerationEU&#8221;</span>&#44; <span class="elsevierStyleGrantSponsor" id="gs3">Mecanismo para la Recuperaci&#243;n y la Resiliencia &#40;MRR&#41;</span> and by &#8220;<span class="elsevierStyleGrantSponsor" id="gs4">Centro de Investigaci&#243;n Biom&#233;dica en Red &#40;CIBER&#41; de Enfermedades Respiratorias</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs4">CB06&#47;06&#47;0037</span>&#41;&#8221; an initiative of the Instituto de Salud Carlos III&#44; Madrid&#44; Spain co-funded by the <span class="elsevierStyleGrantSponsor" id="gs5">European Regional Development Fund&#47;European Social Fund</span> &#40;ERDF&#47;ESF&#44; &#8220;Investing in your future&#8221;&#41;&#46; We thank CERCA Program&#47;Generalitat de Catalunya for institutional support&#46; SM was supported by <span class="elsevierStyleGrantSponsor" id="gs6">Miguel Servet contract</span> &#8220;<span class="elsevierStyleGrantNumber" refid="gs6">CP19&#47;00096</span>&#8221; &#40;ISCIII&#41;&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflict of interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors of this manuscript have no conflicts of interest to disclose&#46;</p></span></span>"
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                  "titulo" => "UTI and AB"
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                  "identificador" => "sec0065"
                  "titulo" => "Kidney transplant-related outcomes"
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                  "identificador" => "sec0070"
                  "titulo" => "Double J cultures"
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    "fechaRecibido" => "2023-05-25"
    "fechaAceptado" => "2023-08-30"
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            0 => "Urinary tract infection"
            1 => "Asymptomatic bacteriuria"
            2 => "Kidney transplant"
            3 => "Mannose"
            4 => "Proanthocyanidins"
            5 => "Prophylaxis"
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          "clase" => "abr"
          "titulo" => "Abbreviations"
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          "palabras" => array:6 [
            0 => "PAC"
            1 => "UTI"
            2 => "AB"
            3 => "KTX"
            4 => "SOT"
            5 => "UC"
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            0 => "Infecci&#243;n del tracto urinario"
            1 => "Bacteriuria asintom&#225;tica"
            2 => "Trasplante renal"
            3 => "Manosa"
            4 => "Proantocianidinas"
            5 => "Profilaxis"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Studies analyzing non-antibiotic alternatives in kidney transplant UTI&#39;s are lacking&#46; <span class="elsevierStyleSmallCaps">d</span>-Mannose&#44; a simple sugar&#44; inhibits bacterial attachment to the urothelium&#44; as does Proanthocyanidins&#59; both could act as a synergic strategy preventing UTI&#59; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This is a pilot prospective&#44; double-blind randomized trial&#46; Sixty de novo kidney transplant recipients were randomized &#40;1&#58;1&#41; to receive a prophylactic strategy based on a 24-h prolonged release formulation of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus Proanthocyanidins vs&#46; Proanthocyanidins &#40;PAC&#41; alone&#46; The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well&#46; The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and&#47;or asymptomatic bacteriuria in the first 6 months post-transplantation&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">27&#37; of patients experienced one UTI episode &#40;cystitis or pyelonephritis&#41; while asymptomatic bacteriuria was very common &#40;57&#37;&#41;&#46; Incidences according UTI type or AB were&#58; 7&#37; vs&#46; 4&#37; for cystitis episode &#40;<span class="elsevierStyleItalic">p</span> 0&#46;3&#41;&#44; 4&#37; vs&#46; 5&#37; for pyelonephritis &#40;<span class="elsevierStyleItalic">p</span> 0&#46;5&#41; and 17&#37; vs&#46; 14&#37; for asymptomatic bacteriuria &#40;<span class="elsevierStyleItalic">p</span> 0&#46;4&#41; for patients in the Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC group vs&#46; PAC group respectively&#46; The most frequent bacteria isolated in both groups was <span class="elsevierStyleItalic">Escherichia coli</span> &#40;28&#37; of all episodes&#41;&#44; UTI or AB due to <span class="elsevierStyleItalic">E&#46; coli</span> was not different according to study group &#40;30&#37; vs&#46; 23&#37; for Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC vs&#46; PAC alone <span class="elsevierStyleItalic">p</span> 0&#46;37&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation&#59; however&#44; the use of <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC does not seem capable to prevent it&#46;</p></span>"
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            "titulo" => "Methods"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Faltan estudios que analicen alternativas no antibi&#243;ticas para tratar las infecciones del tracto urinario &#40;ITU&#41; en los pacientes trasplantados renales&#46; La D-Manosa&#44; un az&#250;car simple&#44; inhibe la adhesi&#243;n bacteriana al urotelio&#44; al igual que las Proantocianidinas&#59; ambas mol&#233;culas podr&#237;an actuar como una estrategia sin&#233;rgica para prevenir las ITUs&#59; pero su eficacia y seguridad a&#250;n no se han evaluado en la poblaci&#243;n trasplantada renal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Este es un ensayo piloto prospectivo y doble ciego&#46; Sesenta receptores de trasplante renal de novo fueron asignados al azar &#40;1&#58;1&#41; para recibir una estrategia profil&#225;ctica basada en una formulaci&#243;n de liberaci&#243;n prolongada de 24 horas de D-Manosa m&#225;s Proantocianidinas &#40;PAC&#41;&#44; frente a solo Proantocianidinas &#40;PAC&#41;&#46; Los suplementos se tomaron durante los primeros 3 meses despu&#233;s del trasplante renal y luego se realiz&#243; un seguimiento durante otros 3 meses&#46; El objetivo principal del estudio fue determinar si la adici&#243;n de D-Manosa a PAC reduc&#237;a la incidencia de ITU y&#47;o bacteriuria asintom&#225;tica en los primeros 6 meses despu&#233;s del trasplante&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El 27&#37; de los pacientes experiment&#243; un episodio de ITU &#40;cistitis o pielonefritis&#41;&#44; mientras que la bacteriuria asintom&#225;tica fue muy com&#250;n &#40;57&#37;&#41;&#46; Las incidencias seg&#250;n el tipo de ITU o bacteriuria asintom&#225;tica fueron&#58; 7&#37; frente a 4&#37; para episodio de cistitis &#40;p 0&#46;3&#41;&#44; 4&#37; frente a 5&#37; para pielonefritis &#40;p 0&#46;5&#41; y 17&#37; frente a 14&#37; para bacteriuria asintom&#225;tica &#40;p 0&#46;4&#41; en el grupo de manosa &#43; PAC frente al grupo PAC&#44; respectivamente&#46; La bacteria m&#225;s frecuente en ambos grupos fue Escherichia coli &#40;28&#37; de todos los episodios&#41;&#44; sin embargo las ITU o bacteriuria asintom&#225;tica debidas a E&#46; coli no fueron diferentes seg&#250;n el grupo de estudio &#40;30&#37; frente a 23&#37; para Manosa &#43; PAC frente a PAC solo&#44; p&#46;0&#46;37&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La terapia no antibi&#243;tica es una necesidad para prevenir las ITU despu&#233;s del trasplante renal&#59; sin embargo&#44; el uso de D-Manosa m&#225;s PAC no parece ser capaz de prevenir las ITU en este grupo especial de pacientes&#46;</p></span>"
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            "apendice" => "<p id="par0235" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix B"
            "titulo" => "Supplementary data"
            "identificador" => "sec0110"
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        "etiqueta" => "Fig&#46; 2"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Number of UTI &#38; AB episodes according to period of study in both groups &#40;<span class="elsevierStyleItalic">p</span> &#46;07&#44; <span class="elsevierStyleItalic">p</span> &#46;07&#44; <span class="elsevierStyleItalic">p</span> &#46;03 respectively for UTI&#59; <span class="elsevierStyleItalic">p</span> &#46;08&#44; <span class="elsevierStyleItalic">p</span> &#46;21&#44; <span class="elsevierStyleItalic">p</span> &#46;07 for AB&#41;&#46; Patients in periods 1 and 2 were taking <span class="elsevierStyleSmallCaps">d</span>-Mannose plus PAC or PAC alone according to study group&#46;</p>"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">PAC&#44; Proanthocyanidins&#59; ESKD&#44; end stage kidney decease&#59; ADPKD&#44; autosomic dominant polycystic kidney decease&#59; CMV&#44; cytomegalovirus&#46;</p>"
          "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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PAC <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sex&#44; &#40;F&#47;M&#41;&#44; n &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#47;14 &#40;48&#47;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#47;15 &#40;44&#47;55&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#41; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#91;49&#8211;69&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#91;50&#8211;70&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Waiting time on dialysis &#40;months&#41;&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#91;20&#8211;54&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#91;17&#46;7&#8211;39&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Cause of ESKD</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Undetermined&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;22&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;11&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;11&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Vascular nephropathy&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tubulo-interstitial nephritis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;11&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ADPKD&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;25&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glomerulonephritis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;29&#46;96&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;25&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;14&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Type of donor&#44; n &#40;&#37;&#41;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Living donor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;4&#37;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DBD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DCD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;59&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Induction therapy&#44; n &#40;&#37;&#41;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Basiliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thymoglobulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;48&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3594695.png"
              ]
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Baseline demographics and clinical characteristics depending on treatment group&#46;</p>"
        ]
      ]
      4 => array:8 [
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">UTI&#44; urinary Tract infections&#59; AB&#44; asymptomatic bacteriuria&#59; PAC&#44; Proanthocyanidin&#46;</p>"
          "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="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC &#40;<span class="elsevierStyleItalic">n</span> 27&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PAC &#40;<span class="elsevierStyleItalic">n</span> 27&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Primary endpoint&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#47;10 &#40;63&#47;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#47;11 &#40;60&#47;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">UTI</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cystitis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pyelonephritis&#44; <span class="elsevierStyleItalic">n</span> &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;18&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>With bacteremia&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;14&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">AB&#44; n &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;63&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Recurrent UTI&#44; n &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Primary endpoint&#44; UTI&#44; AB and recurrent UTI &#40;expressed as number of patients with at least one episode&#41; by treatment group&#46;</p>"
        ]
      ]
      5 => array:8 [
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        "etiqueta" => "Table 4"
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">UTI&#44; urinary tract infections&#59; PAC&#44; Proanthocyanidins&#59; Others &#40;<span class="elsevierStyleItalic">Candida albicans</span>&#44; <span class="elsevierStyleItalic">Proteus mirabilis</span>&#44; <span class="elsevierStyleItalic">Morganella morganii</span>&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#41;&#46;</p>"
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            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="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bacteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mannose PAC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PAC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Escherichia coli</span> &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Klebsiella pneumoniae</span> &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pseudomonas</span> spp&#46; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Enterococcus faecalis</span> &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Enterobacter cloacae</span> &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;42&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Others &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcomes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mannose<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>PAC <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;75&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5 &#40;18&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">7 &#40;25&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;74&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute urine retention&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ureteral reintervention<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lithiasis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Obstructive lymphocele&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>eGFR &#40;&#956;mol&#47;L&#41; 6 months&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Time until catheter extraction&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">24 &#91;22&#8211;27&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">24 &#91;21&#8211;26&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;99&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">CMV viremia&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;29&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">8 &#40;29&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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