Role of urinary biomarkers in the diagnosis of congenital upper urinary tract obstruction

Abstract

Background: Congenital obstructive uropathy constitutes a significant cause of morbidity in children. Currently, there is no reference standard for the diagnosis of renal obstruction in children. The noninvasive measurement of biomarkers in voided urine has considerable appeal as a potential application in children with congenital obstructive nephropathy. The aim of the present review is to explore the current role of biomarkers in the diagnosis and follow-up of obstructive uropathy in children.

Materials and methods: The literature database (PubMed) was searched from inception to May 2007 regarding the role of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy.

Results: The review included 23 experimental and 33 prospective controlled clinical studies. Several cytokines, peptides, enzymes and microproteins were identified as major contributors to or ensuing from obstruction-induced renal fibrosis and apoptosis. The most important biomarkers were transforming growth factor-beta(1) (TGFbeta(1)), epidermal growth factor (EGF), endothelin-1 (ET-1), urinary tubular enzymes [N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)], and microproteins [beta(2)-microglobulin (beta(2)M), microalbumin (M. Alb) and micrototal protein (M.TP)]. All biomarkers showed different degrees of success but the most promising markers were TGFbeta(1), ET-1 and a panel of tubular enzymes. These biomarkers showed sensitivity of 74.3% to 100%, specificity of 80% to 90% and overall accuracy of 81.5% to 94% in the diagnosis of congenital obstructive uropathy in children. Moreover, some of the markers were valuable in differentiation between dilated non-obstructed kidneys in need of conservative management and obstructed kidneys in need of surgical correction. Some studies demonstrated that urinary biomarkers are helpful in the evaluation of success of treatment of children with congenital renal obstruction. Some limitations of the previous studies include lack of different types of controls and small sample size. Larger studies with variable controls are invited to confirm the clinical usefulness of biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy.

Conclusion: Urinary biomarkers are a promising tool that could be used as a noninvasive assessment of congenital renal obstruction in children.

Keywords: Children; kidney; obstruction; urine.