Tubulointerstitial injury of Thy-1 nephritis in uninephrectomized stroke-prone spontaneously hypertensive rats.

Thy-1 nephritis was induced in stroke-prone spontaneously hypertensive rats (SHR-SP) with unilateral nephrectomy (UNX) and normotensive same genetic strain Wistar-Kyoto (WKY) rats with UNX to evaluate whether the tubulointerstitial injury in Thy-1 nephritis is accelerated by long-term systemic and intraglomerular hypertension. SHR-SP that underwent UNX at twelve weeks of age were randomly assigned to receive monoclonal anti-thy 1.1 antibody (group SP), and normal saline (group SC). Age-matched normotensive WKY rats served as controls and were given the same dose of monoclonal anti-thy 1.1 antibody after UNX (group WK). In all groups, the blood pressure and renal function were assessed, and morphologic changes of tubulointerstitium were examined by using immunohistochemistry and light microscopy twelve weeks after Thy-1 nephritis induction (in groups SP and WK) and UNX alone (in group SC). In all groups, histological findings, the degree of monocyte/macrophage infiltration, interstitial expression of alpha-smooth muscle actin (alpha-SMA), which is a marker for myofibroblasts, and the degree of tubular cell proliferation were examined. In addition, assessments of blood pressure, serum creatinine and BUN levels, and the degree of proteinuria were made. In parallel to glomerular structural damage, interstitial fibrosis with predominant monocyte/macrophage influx, increased interstitial expression of alpha-SMA and tubular cell proliferation were observed in group SP. A significant increase in serum creatinine and proteinuria were also present in this group. In contrast, the changes observed in group SC were not so evident or extensive as in group SP. The level of proteinuria was lower than that in group SP. No evident tubulointerstitial changes were found in group WK. The results showed that tubulointerstitial injury was prominently progressed in the hypertensive model with Thy-1 nephritis. This suggests that sustained systemic and glomerular hypertension is not only ultimately responsible for the progression of immunologically mediated glomerular injury, but is also responsible for subsequent tubulointerstitial changes. Migration and proliferation of myofibroblasts and intense influx of monocytes/macrophages may contribute to the development of tubulointerstitial fibrosis.