Toll-like receptor (TLR2, TLR4) polymorphisms and their influence on the incidence of urinary tract infections in children with and without urinary tract malformation.

Introduction: Toll-like receptors (TLRs) contribute to the innate immune system. They are an element of non-specific immunity, which enables organisms to react quickly to foreign antigens, without being previously exposed to them. TLRs are pattern recognition receptors. TLR gene polymorphisms are widely investigated in connection with various infections. The aims of the study were: to investigate the role of TLR2 and TLR4 polymorphisms in the course of urinary tract infections (UTIs); to test for differences in distribution of these polymorphisms between children with urinary tract malformations suffering from recurrent UTI (rUTI), children with malformations but without rUTI and healthy controls; to determine whether these polymorphisms predispose to rUTI; and to analyse how polymorphisms and urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin 8 (IL-8) concentrations affect one another. Material and methods: The group consisted of 133 children (1-18 years old), 68 female and 65 male. The group was divided into 4 subgroups: A (rUTI with urinary tract malformations), B (urinary tract malformations without rUTI), C (rUTI) and D (healthy controls). Polymorphisms were analysed using PCR-RFLP. IL-8 and NGAL urine concentrations were established using immunoenzymatic methods. Results: TLR2 Arg753Gln and TLR4 Arg299Gly appeared significantly more often among children with rUTI. No correlation between urine IL-8 and urine NGAL and polymorphisms was found. Urine NGAL concentration was significantly higher among children with urinary tract malformations. Conclusions: TLR2 Arg753Gln and TLR4 Asp299Gly may predispose to rUTI. Urine NGAL concentration suggests the presence of kidney tissue injury, of varying degrees, among children with urinary tract malformations.

Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

Evaluation of the effect of 3-month bladder basic advice in children with monosymptomatic nocturnal enuresis.

INTRODUCTION: Advice (BBA) into the standards of patients' care in both monosymptomatic and non-monosymptomatic nocturnal enuresis. Although the idea of this recommendation was clear and reflects clinical experience, duration and efficacy have not been definitely established. Recent data have demonstrated the lack of efficacy of BBA and a fierce discussion has ensued. The present study was aimed to assess the efficacy of BBA in a group of previously untreated children with primary monosymptomatic nocturnal enuresis (MNE). STUDY DESIGN: The study was a prospective interventional multicenter trial in a cohort of previously untreated MNE patients. Forty-nine children (36 males, 13 females, mean age 7.2 years) were included in the analysis. The treatment efficacy was assessed at the 30th, 60th, and 90th days of BBA. RESULTS: We discovered that the mean number of wet nights decreased significantly (p < 0.001) only after 3 months of BBA from 8.9 to 5.9 episodes every 2 weeks. BBA was fully successful in 2% o the children after 30 day, 12% after 60 days, and 18% after 90 days (Figure). Partial response (by ICCS) was assessed for 8%, 20%, and 34% of the patients. We noted a relatively high rate of non-responders that decreased from 90% to 47% after 90 days. We detected no differences in BBA efficacy between children with night-time polyuria or decreased maximal voided volume. A lower number of wet nights initially predicted the response to the BBA. DISCUSSION: Our study confirmed rather limited efficacy of BBA, similarly to previous observations, but provided more information on isolated MNE, because of a more specific study group and longer period of observation. The limitation of the study was lack of randomization. CONCLUSION: Our study revealed that in treatment-naïve children with monosymptomatic enuresis basic bladder training had a low (18%) and late effect, mostly pronounced after the third month of therapy. It seems that only if the patient presents with a favorable profile of bedwetting, occasionally and with a high maximum voided volume, it is worth maintaining BBA for a longer period of up to 3 months before initiating second-line therapy. In an unfavorable initial profile desmopressin or an alarm may be introduced much earlier.