title: [Pathophysiology and clinical implication of obstructive nephropathy].
abstract: Obstructive nephropathy refers to the mechanical or functional changes in the urinary tract that interfere with normal urinary flow. Once obstruction is set, it leads to progressive renal damage that is mainly characterized with tubulointerstitial fibrosis. Here we reviewed the pathophysiology of urinary tract obstruction and indicated future therapeutic options. Following complete unilateral ureteral obstruction, there is a progressive fall in renal blood flow and glomerular filtration rate, and is a increase in intratubular pressure. These events activate the plasma and tissue renin-angiotensin systems (RAS). It has been proved that upregulated angiotensin II is one of the crucial factors those are responsible for the subsequent deleterious process. Angiotensin II induces transforming growth factor-beta, which causes overproduction of extracellular matrix (ECM) proteins like collagen, fibronectin, etc. The ECM proteins are dominantly accumulated in tubulointerstitium and result in deterioration of renal function. Along with the activation of the RAS, tissue ischemia and mononuclear leukocyte infiltration also modulate the fibrotic changes. The process from the RAS activation to renal fibrosis is observed not only in obstructive nephropathy but also in other renal diseases and is called the Final Common Pathway. Mechanical release of the obstruction is to perform in terms of the treatment, however, several promising pharmaceutical options are now under investigation.
authors.affiliation: Department of Urology, Tohoku University Graduate School of Medicine.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ishidoya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukuzaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Ogata
authors.forename: Haruo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Orikasa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D005355:Fibrosis / Q000209:etiology; D006801:Humans; D006869:Hydronephrosis / Q000209:etiology; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D012079:Renal Circulation; D012084:Renin-Angiotensin System / Q000502:physiology; D014517:Ureteral Obstruction / Q000503:physiopathology*
chemical_list: D011945:Receptors, Angiotensin; D000804:Angiotensin II