Nordenström Josefin, Sjöström Sofia, Sillén Ulla, Sixt Rune, Brandström Per
Department of Paediatric Surgery, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Paediatric Surgery, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
J Pediatr Urol. 2017 Apr;13(2):146-154. doi: 10.1016/j.jpurol.2016.12.023. Epub 2017 Feb 2.
High-grade vesicoureteral reflux (VUR) in children is associated with recurrent urinary tract infection (UTI) and renal damage. Breakthrough UTI despite continuous antibiotic prophylaxis (CAP) during the first years of life is a matter of concern and evokes early intervention. We investigated whether early endoscopic treatment (ET) of VUR grade 4-5 can reduce the risk of UTI recurrence and renal scarring.
This prospective, randomized, controlled, multicentre, 1-year follow-up trial comprised 77 infants, <8 months of age with VUR grade 4-5 (Table) randomized to CAP (n = 39) or ET (with prophylaxis until resolution) (n = 38). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year. Parenchymal defects were seen in 67 (87%) children at entry, 39 (34 boys, 5 girls) of them characterized as generalized. At follow-up, renal deterioration (new scars or progress in old damaged area) and symptomatic UTIs were reported.
There were 27 recurrent febrile UTIs in 6 (16%) children in the ET group and in 10 (26%) in the CAP group (p = 0.43), in eight (36%) girls and eight (15%) boys (p = 0.039). Successful VUR outcome (VUR 0-2) was seen in 22 (59%) in the ET and eight (21%) in the CAP group (p = 0.0014). Multiple recurrences were only seen in patients with persistent dilating reflux at follow-up (p = 0.019). Deterioration on scintigraphy was seen in eight children (9 kidneys) with no difference between treatment groups (p = 0.48) or sex (p = 0.17). Renal deterioration was associated with high bladder capacity (BC) and large residual volume (PVR) at 1 year (p = 0.0092 and p = 0.041). Six of the eight children with renal deterioration had a recurrent UTI (p = 0.0032). Seven of nine renal units with deterioration were seen in children with persistent VUR 3-5 at follow-up. Univariable logistic regression identified female sex and high PVR as positive predictors for recurrent UTI (p = 0.039 and 0.034) and high PVR tended to predict renal deterioration (p = 0.053).
No differences between the treatment groups regarding recurrent UTI and renal deterioration could be found. Increased PVR and female sex were positive predictors for UTI recurrences. VUR grade at follow-up was correlated to UTI recurrence and renal deterioration.
This study did not show any difference between ET and CAP in reducing the risk of UTI recurrence or renal deterioration. The rate of VUR resolution was higher in the ET group and VUR grade at follow-up correlated with both UTI recurrence and renal deterioration.
儿童重度膀胱输尿管反流（VUR）与复发性尿路感染（UTI）及肾损害相关。尽管在生命的最初几年进行了持续抗生素预防（CAP），仍发生突破性UTI是一个值得关注的问题，并促使早期干预。我们研究了4 - 5级VUR的早期内镜治疗（ET）是否能降低UTI复发和肾瘢痕形成的风险。
这项前瞻性、随机、对照、多中心、为期1年的随访试验纳入了77名年龄小于8个月、VUR为4 - 5级的婴儿（表），随机分为CAP组（n = 39）或ET组（预防性治疗直至反流消失）（n = 38）。在研究开始时和1年后进行排尿性膀胱尿道造影、超声、肾闪烁显像及自由排尿观察。67名（87%）儿童在入组时发现实质缺损，其中39名（34名男孩，5名女孩）表现为广泛性缺损。随访时，报告了肾恶化（新瘢痕或旧损伤区域进展）和有症状的UTI情况。
ET组6名（16%）儿童和CAP组10名（26%）儿童发生了27次复发性发热性UTI（p = 0.43），其中8名（36%）女孩和8名（15%）男孩（p = 0.039）。ET组22名（59%）和CAP组8名（21%）患者的VUR治疗成功（VUR 0 - 2级）（p = 0.0014）。仅在随访时持续性扩张性反流患者中出现多次复发（p = 0.019）。8名儿童（9个肾脏）肾闪烁显像出现恶化，治疗组之间（p = 0.48）或性别之间（p = 0.17）无差异。肾恶化与1年时高膀胱容量（BC）和大量残余尿量（PVR）相关（p = 0.0092和p = 0.041）。8名肾恶化儿童中有6名发生复发性UTI（p = 0.0032）。随访时持续性VUR 3 - 5级儿童中，9个恶化肾单位中有7个出现恶化。单因素逻辑回归分析确定女性性别和高PVR是复发性UTI的阳性预测因素（p = 0.039和0.034），高PVR倾向于预测肾恶化（p = 0.053）。
在复发性UTI和肾恶化方面，治疗组之间未发现差异。PVR增加和女性性别是UTI复发的阳性预测因素。随访时的VUR分级与UTI复发和肾恶化相关。
本研究未显示ET和CAP在降低UTI复发风险或肾恶化方面有任何差异。ET组VUR消失率更高，随访时的VUR分级与UTI复发和肾恶化均相关。
