Nordenström Josefin, Holmdahl Gundela, Brandström Per, Sixt Rune, Stokland Eira, Sillén Ulla, Sjöström Sofia
Department of Paediatric Surgery, Paediatric Uronephrologic Centre, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Paediatric Surgery, Paediatric Uronephrologic Centre, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
J Pediatr Urol. 2017 Apr;13(2):130-138. doi: 10.1016/j.jpurol.2016.08.026. Epub 2016 Oct 24.
High-grade vesicoureteral reflux (VUR) in infants is associated with congenital renal abnormalities, recurrent UTI, and bladder dysfunction. Endoscopic treatment (ET) is a well-established method in children with low to moderate reflux grades, but there is a lack of randomised controlled trials regarding the use of ET versus continuous antibiotic prophylaxis in infants with high-grade VUR.
This study aimed to determine whether high-grade VUR in infants can be treated with endoscopic injection and whether ET is superior to antibiotic prophylaxis in the treatment of VUR.
This prospective, randomised, controlled, multicentre, 1-year follow-up trial comprised 77 infants (55 boys, 22 girls) <8 months of age with VUR grade 4-5 (n = 30/n = 47). Of the infants, 52 (68%) had bilateral VUR. Thirty-nine were randomised to antibiotic prophylaxis and 38 to ET (with prophylaxis until resolution). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year to evaluate VUR grade, and renal and bladder function.
VUR grade ≤2 was seen in 22 (59%) infants in the endoscopy group and eight (21%) in the prophylaxis group at follow-up (p = 0.0014). The success rate in the endoscopy group was 100% in unilateral grade 4, falling to 31% in bilateral grade 5 (p = 0.0094). Correspondingly, the results in the prophylaxis group were 40% in grade 4 down to 0% in bilateral grade 5 (p = 0.037) (Table). Logistic regression analyses identified ET, VUR grade 4, unilaterality, and low residual urine at baseline as positive predictors of VUR down-grading to ≤2 (area under ROC curve 0.88). In four patients with reflux resolution after one injection, dilating reflux recurred at the 1-year follow-up. One patient had a UTI possibly related to ET. In our material four patients required re-implantation, of whom one was obstructive after injection.
The opportunity to offer even small infants with high-grade VUR an alternative, minimally invasive treatment option is a great advance in paediatric urology. In this high-risk group, bilateral VUR grade 5 stands out with its poor bladder function and low chance of resolution. The recurrence rate of dilating VUR after successful ET is consistent with previous studies. The limitations are the relatively small number of patients and the short follow-up.
High-grade VUR in infants can be treated with injection therapy and the resolution rate is higher than that of prophylaxis treatment. The complication rate is low and VUR grade 4, unilaterality, and low residual urine are favourable for the resolution and down-grading of VUR.
婴儿重度膀胱输尿管反流（VUR）与先天性肾脏异常、复发性尿路感染及膀胱功能障碍有关。内镜治疗（ET）是治疗轻至中度反流分级儿童的成熟方法，但对于重度VUR婴儿，使用ET与持续抗生素预防相比，缺乏随机对照试验。
本研究旨在确定婴儿重度VUR能否通过内镜注射治疗，以及ET在治疗VUR方面是否优于抗生素预防。
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例年龄小于8个月、VUR分级为4-5级（n = 30/n = 47）的婴儿（55例男孩，22例女孩）。其中，52例（68%）为双侧VUR。39例随机接受抗生素预防，38例接受ET（预防至反流消失）。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，以评估VUR分级、肾脏和膀胱功能。
随访时，内镜治疗组22例（59%）婴儿VUR分级≤2级，预防组8例（21%）（p = 0.0014）。内镜治疗组单侧4级VUR成功率为100%，双侧5级降至31%（p = 0.0094）。相应地，预防组4级为40%，双侧5级降至0%（p = 0.037）（表）。逻辑回归分析确定ET、VUR 4级、单侧性及基线时残余尿量少是VUR降级至≤2级的阳性预测因素（ROC曲线下面积为0.88）。4例单次注射后反流消失的患者，在1年随访时扩张性反流复发。1例患者发生可能与ET相关的尿路感染。在我们的研究资料中，4例患者需要再次植入，其中1例注射后出现梗阻。
为即使是重度VUR的小婴儿提供另一种微创治疗选择，这在小儿泌尿外科是一项重大进展。在这个高危组中，双侧5级VUR因其膀胱功能差和消失机会低而突出。ET成功后扩张性VUR的复发率与先前研究一致。局限性在于患者数量相对较少且随访时间短。
婴儿重度VUR可采用注射治疗，治愈率高于预防治疗。并发症发生率低，VUR 4级、单侧性及残余尿量少有利于VUR的治愈和降级。
