Obstructive renal injury: from fluid mechanics to molecular cell biology

Abstract

Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

Keywords: fluid mechanics; molecular cell biology; renal injury; urinary tract obstruction.

Figure 1

Schematic representation of the enzymatic pathways involved in the generation of angiotensin peptides. Abbreviations: ACE, angiotensin-converting enzyme; AMP, aminopeptidase; AT1, Ang II type 1 receptor; AT2, Ang II type 2 receptor; AT4, Ang IV receptor; MAS, Ang-(1-7)receptor; IRAP, insulin-regulated aminopeptidase; PCP, prolyl-carboxypeptidase; PEP, prolyl-endopeptidase; NEP, neutral-endopeptidase.

Figure 2

Unilateral ureteral obstruction (UUO) processes and molecules. Representation of interconnections between the different processes in UUO and the main molecules involved.