Clinic of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Pediatrics. 2012 Feb;129(2):e356-63. doi: 10.1542/peds.2010-3467. Epub 2012 Jan 23.
High-grade vesicoureteral reflux (VUR, grade IV or V) is a risk factor for renal scarring, impaired renal function, and arterial hypertension. Voiding cystourethrography is the gold standard for detecting the severity of VUR. High-grade VUR is present in the minority of children with urinary tract infection (UTI), thus exposing the majority to invasive diagnostics that have no surgical consequence. We therefore aimed at establishing a noninvasive test to identify children with high-grade VUR.
In a case-control study, a specific urinary proteome pattern was established by capillary electrophoresis coupled to mass spectrometry in 18 patients with primary VUR grade IV or V, distinguishing these from 19 patients without VUR after UTI. This proteome pattern was independently validated in a blinded cohort of 17 patients with VUR grade IV or V and 19 patients without VUR.
Sensitivity in detecting VUR grade IV or V in the blinded study was 88%, specificity was 79%. The test's accuracy was independent of age, gender, and grade of VUR in the contralateral kidney. The odds ratio of suffering from VUR grade IV or V when tested positive was 28 (95% confidence interval: 4.5 to 176.0).
This noninvasive test is ready for prospective validation in large cohorts with the aim of identifying those children with UTI and hydronephrosis in need of further invasive diagnostics, such as voiding cystourethrography, thus sparing most children without pathologic urinary proteome patterns from additional diagnostics.
高级膀胱输尿管反流（VUR，IV 或 V 级）是肾瘢痕形成、肾功能受损和动脉高血压的危险因素。排尿性膀胱尿道造影是检测 VUR 严重程度的金标准。在患有尿路感染（UTI）的儿童中，只有少数存在高级别 VUR，因此大多数儿童需要接受无手术后果的侵入性诊断。因此，我们旨在建立一种非侵入性测试来识别患有高级别 VUR 的儿童。
在一项病例对照研究中，通过毛细管电泳与质谱联用技术在 18 例原发性 VUR IV 或 V 级的患者中建立了特定的尿蛋白质组模式，将其与 19 例 UTI 后无 VUR 的患者区分开来。该蛋白质组模式在 17 例 VUR IV 或 V 级和 19 例无 VUR 的患者的盲法队列中得到了独立验证。
在盲法研究中，检测 VUR IV 或 V 级的敏感性为 88%，特异性为 79%。该测试的准确性与年龄、性别和对侧肾脏的 VUR 分级无关。当测试结果为阳性时，患 VUR IV 或 V 级的几率为 28（95%置信区间：4.5 至 176.0）。
这种非侵入性测试已准备好在大样本队列中进行前瞻性验证，目的是识别那些患有 UTI 和肾积水需要进一步侵入性诊断（如排尿性膀胱尿道造影）的儿童，从而使大多数无病理性尿液蛋白质组模式的儿童免于进一步的诊断。
