Effect of chronic salt loading on kidney function in early and established diabetes mellitus in rats

Abstract

Glomerular hyperfiltration and renal hypertrophy are among the events that characterize the early course of diabetes mellitus in rats and human patients. Previous studies from this laboratory demonstrated that salt restriction paradoxically reduces total renal vascular resistance (RVR) and increases glomerular filtration rate (GFR) in diabetic rats (J Am Soc Nephrol 1995;5: 1761-7). In the present study we examined the converse condition by testing the effects of chronic salt loading on kidney function in moderately hyperglycemic insulin-treated rats with early and restablished streptozotocin diabetes. Salt loading was accomplished by adding 1% NaCl to the drinking water 1 day or 35 days after diabetes was induced. The high-salt diet appropriately increased salt excretion in diabetic rats and nondiabetic controls. GFR and renal plasma flow were determined by inulin and para-amino hippuric acid (PAH) clearance 7 days after salt loading was started. Diabetic rats receiving tap water exhibited hyperfiltration with no change in renal blood flow (RBF). In nondiabetic rats, salt loading caused a reduction in total RVR and proportional increases in RBF, GFR, and kidney weight (KW). Salt loading in early diabetes did not affect RVR, RBF, or KW and caused a paradoxical reduction in GFR. In established diabetes, salt loading reduced RVR and increased RBF, similar to results in nondiabetic rats, but as in rats with early diabetes, it did not increase GFR or KW. In summary, although the response in RVR and RBF to chronic salt loading depends on the duration of diabetes, the increase in GFR and KW as seen in nondiabetic rats is blunted in the early and established state of insulin-treated diabetes in rats. These findings further support the notion that the renal response to variation in salt intake is altered in insulin-treated diabetes in rats.