BIOMARKERS OF CONGENITAL OBSTRUCTIVE NEPHROPATHY: PAST, PRESENT AND FUTURE

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Abstract
Purpose: Congenital obstructive nephropathy constitutes one of the major causes of renal insufficiency in infants and children. This review addresses the need to define biomarkers that serve as surrogate end points for measuring the severity of obstruction, the evolution of renal maldevelopment and injury, and the response to medical or surgical intervention. Materials and Methods: The literature from the last 10 years was reviewed for biomarkers of congenital obstructive nephropathy. Sources of biomarkers included urine, blood, amniotic fluid, tissue and imaging techniques. Results: Previous markers of congenital obstructive nephropathy include sonographic renal pelvic diameter, quantitative diuretic renography, and markers of glomerular and tubular function. Attempts to correlate renal histological changes with differential renal function have been disappointing. Immunohistochemical analysis and laser capture microscopy should improve specificity. Most promising is the application of new insights into the cellular response of the developing kidney to urinary tract obstruction. These findings include components of the renin-angiotensin system, transforming growth factor-β 1, monocyte chemoattractant protein-1 and epidermal growth factor. Microarray studies show unique patterns of gene expression by the neonatal rat kidney subjected to ureteral obstruction, and proteomics should provide even more sensitive biomarkers of obstructive nephropathy. Conclusions: We must define the cellular and molecular bases of renal maldevelopment, focusing on the link between functional and developmental pathophysiology. These findings will lead to biomarkers that will optimize our management of congenital obstructive nephropathy.