Reflux nephropathy has been extensively studied in a pig experimental model; the pig has been used because it has compound papillae at the renal poles as humans do. Radiographic and pathologic studies have demonstrated that refluxing urine can gain access to the parenchyma in these locations. The compound papillae have large ducts of Bellini into which refluxed material can enter; the broad openings of these ducts do not prevent this process as the smaller more angulated duct openings of simple papillae do. The refluxing urine can induce tubular rupture with extravasation of the tubular contents, or may cause forniceal tears with direct extension of urine into the parenchyma. This process of pyelotubular backflow is known as intrarenal reflux. There is local damage in response to the extravasated material, with scar formation occurring within 1 to 2 weeks in the pig model. While some investigators have proposed that the urinary contents alone are adequate to induce scar formation, it is more widely believed that some element of infection is required to produce chronic interstitial nephritis. Refluxing urine, usually resulting from inadequate length or abnormal positioning of the ureterovesical junction orifice, is a common mechanism. Studies suggest that nitric oxide stimulated by macrophage colony-stimulating factor may be a major mediator of tissue damage in reflux nephropathy (6). Children under the age of 5 have shorter ureters and more patent ducts of Bellini, and therefore are more prone to develop reflux nephropathy. In fact, many polar scars occur prior to the age of 4 or 5 years, and do not substantially worsen after that time as the intravesical ureter lengthens and reflux subsides. As the scarring occurs, a component of arterial intimal fibrosis often ensues, with additional damage resulting from ischemia.
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