Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review

Antenatal hydronephrosis is a common finding detected on prenatal ultrasound. Although hydronephrosis will spontaneously resolve in the majority of newborns, there is a significant amount of cases that will worsen with the risk of a progressive and permanent loss of renal function. There is an increasing concern among experts that the current criteria for evaluation of clinically significant obstructions are limited. Our aim is to provide a systematic review of the available literature on biomarkers of renal injury, potential targets for diagnosis and prognosis of children with hydronephrosis. The main search was conducted in the electronic databases from inception through March 2019 using various combinations of the keywords: pelvic-ureteric [All Fields] AND junction [All Fields] AND obstruction [All Fields] AND “biomarkers” [MeSH Terms] OR “biomarkers” [All Fields] OR “biomarker” [All Fields]. To broaden the research, additional articles were identified through hand-searching review of the references reported in each study previously selected. Histopathological studies, studies with no control group or with participants suffering from concomitant urological diseases and articles published in language other than English were excluded. Data on study design, sample size, average patient age, hydronephrosis definition used, surgical indication, duration and pattern of follow-up, details on biomarker studied, diagnostic test characteristics, area under the curve (AUC) on receiver operating characteristic (ROC) analysis with the best cut-off (BCO) values, sensitivity, specificity and outcomes were all collected. 38 articles analysing 41 biomarkers were selected. The most frequent proteins investigated were neutrophil gelatinase-associated lipocalin (NGAL) (n=9; 23.7%), monocyte chemotactic peptide-1 (MCP1) (n=8; 21.1%), transforming growth factor β1 (TGFβ1) (n=7; 18.4%), epidermal growth factor (EGF) (n=6; 15.8%) and kidney injury molecule 1 (KIM 1) (n=6; 15.8%). Twenty-seven (71.1%) studies evaluated the effect of pyeloplasty on voided urine biomarker concentrations, comparing their values before and after surgery. Twelve (31.6%) studies investigated the correlation between preoperative biomarker concentration and the anterior posterior renal pelvis diameter (DAP) while 20 (52.6%) studies investigated the correlation between preoperative biomarker concentration with the split renal function (SRF) measured on nuclear medicine assessments. ROC curves were used to investigate the performance of urinary biomarkers in the total patient data set in 27 (71.1%) studies. Some biomarkers offer promising results. However, a critic analysis of the published studies demonstrates bias and lack of consistency suggesting that larger multicentre and carefully designed prospective studies are still needed to evaluate the clinical usefulness of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive hydronephrosis.