The molecular biology of pelvi-ureteric junction obstruction

Abstract

Over recent years routine ultrasound scanning has identified increasing numbers of neonates as having hydronephrosis and pelvi-ureteric junction obstruction (PUJO). This patient group presents a diagnostic and management challenge for paediatric nephrologists and urologists. In this review we consider the known molecular mechanisms underpinning PUJO and review the potential of utilising this information to develop novel therapeutics and diagnostic biomarkers to improve the care of children with this disorder.

The Genomic Response to TGF-β1 Dictates Failed Repair and Progression of Fibrotic Disease in the Obstructed Kidney

“…Unilateral ureteral obstruction (UUO) in rodents (e.g., Chevalier, 2015;Martínez-Klimova et al, 2019), for example, closely mirrors (in an accelerated context) human obstructive nephropathy while bridging the pathologic features of AKI and CKD (Moller et al, 1984;Hruska, 2002;Ucero et al, 2014). Ureteral ligation provides an accessible, translationally-relevant, in vivo opportunity to clarify the genomic complexity of renal fibrotic disease, dissect critical pathophysiologic events underlying the kidney response to injury and identify mechanisms involved in maladaptive repair (Klahr and Morrissey, 2002;Truong et al, 2011;Eddy et al, 2012;Samarakoon et al, 2012;Arvaniti et al, 2016;Sun et al, 2016;Jackson L. et al, 2018;Martínez-Klimova et al, 2019;Pavkovic et al, 2019).…”

“…Partial and complete UUO in neonatal rodents are similar except for a temporal offset in acquisition of pathologic features (Jackson L. et al, 2018;. UUO modeling largely focuses on the proximal tubular compartment due to its high mitochondrial load, dependency on oxidative phosphorylation, susceptibility to ischemic injury and relative deficiency of anti-oxidant/anti-apoptotic factors (Chevalier, 2016).…”

Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction

“…The intrarenal renin–angiotensin–aldosterone system is then activated, which causes pre- and post-glomerular vasoconstriction and resultant drops in renal blood flow, medullary oxygen tension, and the glomerular filtration rate [ 11 , 12 ]. The increased intra-renal angiotensin II activates nuclear factor kappa B, triggering cytokine release and reactive oxygen species (ROS) production [ 2 , 10 , 13 , 14 ]. Adhesion molecules such as selectins attract infiltrating macrophages, monocyte chemotactic protein-1 (MCP-1) is upregulated, and tumor necrosis factor-α (TNF-α) is released.…”

“…Adhesion molecules such as selectins attract infiltrating macrophages, monocyte chemotactic protein-1 (MCP-1) is upregulated, and tumor necrosis factor-α (TNF-α) is released. Monocytes and macrophages are attracted to the tubular interstitium of the UUTO kidney [ 2 , 14 , 15 ]. Activated macrophages infiltrate the interstitium, sustaining the inflammatory response by releasing cytokines such as transforming growth factor-β1 (TGF-β1) and TNF-α and ROS [ 16 ].…”

Minimal Invasive Treatment in Pelvic-Ureteric Junction Obstruction: A Comprehensive Review

“…Nevertheless, it could also manifest or develop (acquired) later during adult life. 3 , 4 Despite various experiments and research, the exact etiology and pathogenesis of PUJO is still unknown. 5 On the other hand, the underlying cause of an acquired PUJO is relatively clearer.…”