Progression of Chronic Pyelonephritis in the Rat

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Abstract
Thirteen of 20 female Wistar rats developed perihilar kidney scars 6 weeks after ascending infection with Escherichia coli 078. After removal of the lesser scarred kidney from 6 of the animals, all animals were followed for 54 weeks. Proteinuria (> 18 mg/24 h) developed at 20 weeks in the uninephrectomised infected rats and at 34 weeks in the 2-kidney infected model. In 10 uninephrectomised controls significant proteinuria did not appear until 52 weeks. In 9 2-kidney controls proteinuria did not develop at all. The speed of onset and severity of proteinuria was related to the extent of the renal parenchymal loss. Pyelonephritic scars did not show macroscopic progression over the 54-week observation period, even though the original renal infection persisted. Uninephrectomised animals with infected scars developed a highly significant rise of creatinine/body weight (p < 0.02) and of heart weight/body weight (p < 0.02) ratios compared with the non-infected controls. Their kidneys showed focal and segmental hyalinosis and sclerosis of the glomeruli adjacent to the scars. Immunofluorescent staining for serum proteins was negative, but mesangial deposits of Tamm-Horsfall protein were found in the glomeruli between the scars in animals with renal impairment. These findings establish that progressive renal impairment in rats with infected kidney scars is associated with the development of proteinuria and a glomerulopathy. The cause of the glomerulopathy is not clear, both glomerular hyperfiltration and deposition of Tamm-Horsfall protein in glomerular mesangial cells may be involved.