Congenital ureteropelvic junction obstruction: human disease and animal models

Abstract

Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin-angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short-coming is the absence of data on the impact of UPJ obstruction on long-term adult renal function to elucidate whether these animal data are also valid in humans.

Figure 1

Histological lesions and functional modifications induced by obstruction.

Figure 2

Renal tubular exposure to hydrodynamic modifications following obstruction. Following intra-pelvic urine accumulation, UUO induces rapid elevation of hydrostatic pressure into the renal tubular lumina, leading to stretch and compression of the tubular cells and thus to tubular dilatation. As GFR declines and tubular dilatation increases, hyperpressure progressively returns to basal levels. However in the mean time, fluid shear stress, which depends on both GFR and tubular diameter, is strongly reduced. Thus modifications of renal hydrodynamics can induce mechanical stimuli such as pressure, shear stress and stretch. These three factors are potential insults for tubular cells and can be involved in the primary induction of the UUO-induced renal lesions.