Ameliorative effects of dietary protein restriction in chronic aminonucleoside nephrosis

Because many investigators have demonstrated the efficacy of dietary protein restriction in various experimental models of glomerular injury that progress to focal and segmental glomerulosclerosis (FSGS), we used this dietary maneuver in chronic aminonucleoside nephrosis. This model of glomerular disease, which uses a single intravenous injection of the puromycin aminonucleoside (PAN), slowly progresses over 18 weeks with mesangial cell proliferation and FSGS as the pathologic hallmarks. We performed renal functional and histopathologic studies in 21 rats with chronic aminonucleoside nephrosis. Group 1 rats (n = 10) were fed a standard rodent diet containing 23.4% protein, whereas group 2 animals (n = 11) were maintained with a 6% protein diet replete with electrolytes, minerals, and vitamins. In those animals subjected to dietary protein restriction, proteinuria was significantly reduced at 14, 28, 84, and 126 days after PAN administration. In rats maintained with the 6% protein diet at 126 days after PAN delivery, there was also a significant reduction in the percent of glomeruli with segmental areas of glomerulosclerosis or hyalinosis and mesangial cell proliferation. We conclude that the renal functional and histologic consequences of chronic aminonucleoside nephrosis can be blunted by dietary protein restriction.