Combining an antiproteinuric approach with mycophenolate mofetil fully suppresses progressive nephropathy of experimental animals

Chronic renal diseases progress to organ insufficiency which may require re placement therapy within one to three decades even independently of the typ e of initial insults. In the majority of cases, the degrees of proteinuria and interstitial leukocyte infiltration and scarring are strictly correlate d with the rate of disease progression. This study tests the hypothesis tha t excess intrarenal protein traffic may cause lymphocyte-dependent intersti tial injury that, while not fully controlled by antiproteinuric therapy, ca n be further inhibited by concomitant immunosuppression. A primarily nonimm une model was used to reproduce progressive renal disease due to a critical loss of nephron mass. Angiotensin-converting enzyme (ACE) inhibitor limite d proteinuria, interstitial inflammation, MHC class II antigen expression, and severe lesions. Combined treatment with ACE inhibitor and a specific an tilymphocyte agent, mycophenolate mofetil, dramatically attenuated macropha ge and T cell infiltration, MHC-class II over; expression, dendritic cells, and all manifestations of the disease. Evidence of lymphocyte-mediated ren al injury in the setting of excess protein traffic provides the basis for c ombining ACE inhibition and immunosuppression to halt progression of protei nuric kidney disease and minimize the need for dialysis or transplantation.