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The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.) [ABSTRACT FROM AUTHOR]

Significance Statement: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.0% of them. We detected no significant differences in the overall diagnostic yield among COU subphenotypes, with characteristic variable expressivity of several mutant genes. Our findings therefore may legitimize a genetic first diagnostic approach for COU, especially when burdening clinical and imaging characterization is not complete or available., Background: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification., Methods: We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction ( n =321), ureterovesical junction obstruction/congenital megaureter ( n =178), and COU not otherwise specified (COU-NOS; n =234)., Results: We identified pathogenic single nucleotide variants (SNVs) in 53 (7.2%) cases and genomic disorders (GDs) in 23 (3.1%) cases. We detected no significant differences in the overall diagnostic yield between COU sub-phenotypes, and pathogenic SNVs in several genes were associated to any of the three categories. Hence, although COU may appear phenotypically heterogeneous, COU phenotypes are likely to share common molecular bases. On the other hand, mutations in TNXB were more often identified in COU-NOS cases, demonstrating the diagnostic challenge in discriminating COU from hydronephrosis secondary to vesicoureteral reflux, particularly when diagnostic imaging is incomplete. Pathogenic SNVs in only six genes were found in more than one individual, supporting high genetic heterogeneity. Finally, convergence between data on SNVs and GDs suggest MYH11 as a dosage-sensitive gene possibly correlating with severity of COU., Conclusions: We established a genomic diagnosis in 10.0% of COU individuals. The findings underscore the urgent need to identify novel genetic susceptibility factors to COU to better define the natural history of the remaining 90% of cases without a molecular diagnosis., (Copyright © 2023 by the American Society of Nephrology.)

Congenital obstructive nephropathy (CON) is one of the most common causes of chronic kidney disease in children. The aim of the study was to investigate serum and urine periostin and cytokeratin-18 (CK-18) in children with CON in relation to CON etiology, treatment, and kidney injury. We evaluated 81 children with CON secondary to ureteropelvic junction obstruction (UPJO), ureterovesical junction obstruction (UVJO), posterior urethral valves (PUV) and 60 controls. Neither biomarker demonstrated any relation to CON etiology. However, all patients showed significantly higher urine periostin (uPeriostin) and uPeriostin/Cr levels than the controls. Also, UVJO patients showed higher sCK-18 and uCK-18/Cr levels, and PUV patients showed higher uCK-18/Cr levels than the controls. Neither biomarker was found to have any relation to CON treatment. However, conservatively treated children and those before and after surgery showed significantly higher uPeriostin and uPeriostin/Cr levels than the controls. uPeriostin strongly correlated with differential renal function (DRF) < 40%. The ROC analysis demonstrated the best area under the curve (AUC) for uPeriostin (0.831) and uPeriostin/Cr (0.768), and low for sPeriostin (0.656) and uCK-18 (0.615) for detecting renal injury. In conclusion, although serum and urine periostin and CK-18 did not display any relation to etiology or the type of CON treatment, uPeriostin seems to be a useful tool for detecting renal injury in children with CON, especially due to its strong negative correlation with DRF < 40%., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)