Effect of aspirin on experimental diabetic nephropathy

The decline in glomerular filtration rate (GFR) in long-term diabetes in humans and animals in preceded by a period of hyperfiltration that may be responsible for it. The mediators of the increase in glomerular filtration are unknown, but recent studies suggest a prominent role for prostaglandins. To test the hypothesis that prostaglandins mediate early hyperfiltration and contribute to the progression of diabetic nephropathy, we examined the effects of long-term aspirin (ASA) treatment on whole kidney GFR and renal prostaglandin E2 (PGE2) synthesis in control and diabetic rats 8 days and 16 weeks after streptozocin administration. The rats were divided into four groups, control, control with ASA (C/ASA), diabetic, and diabetic with ASA (D/ASA). We found that 8 days after streptozocin treatment, PGE2 synthesis and GFR were increased in diabetic rats. ASA treatment inhibited renal prostaglandin synthesis and prevented the GFR increase. ASA given to control rats reduced PGE2 synthesis without changing GFR. In the 16-week study diabetic rats had lower GFR and increased renal PGE2 synthesis. Diabetic rats also had thickened glomerular basement membrane compared with control rats. By contrast GFR did not fall and thickening of the glomerular basement membrane did not occur in diabetic rats receiving ASA. ASA had no effect on GFR or glomerular basement membrane in normal rats but decreased renal PGE2 synthesis. The data demonstrate that aspirin prevents early hyperfiltration and prevents the fall in GFR and glomerular basement membrane thickening that occurs over time in diabetic rats. Inhibition of PGE2 synthesis by aspirin, or some other effect of aspirin, may be responsible for the protection observed.