Proteinuria is the clinical hallmark of
diabetic nephropathy and the harbinger of progressive renal disease. Therefore, the present study was designed to examine the effect of
phosphate restriction on the
proteinuria of
streptozotocin-induced
diabetes mellitus in the rat. Uninephrectomy was performed in experimental and control groups to worsen the degree of
diabetic nephropathy.
Proteinuria was prevented in Sprague-Dawley rats treated with the intestinal
phosphate binder,
dihydroxyaluminum aminoacetate (
DHAAA) (24.75 +/- 20.35 mg/
d at 3 months v control, 77.45 +/- 44.72 mg/d, P less than 0.001); an effect that was independent of
protein and caloric intake,
plasma albumin and
lipids, severity of diabetes, mean arterial pressures, cardiac output, and renal
calcium accumulation. The effect of
DHAAA on
protein excretion and glomerular hemodynamics was examined in similarly prepared Munich-Wistar rats; these rats did not tolerate long-term studies. Three weeks of
DHAAA again caused a consistent fall in
proteinuria (5.98 +/- 7.28 v 34.94 +/- 24.28 mg/d) and in transmembrane hydraulic pressure difference (41.1 +/- 1.2 v 46.4 +/- 2.8 mm Hg, P less than 0.005). In conclusion,
phosphate restriction significantly decreases the
proteinuria of Sprague-Dawley and Munich-Wistar uninephrectomized rats with
streptozotocin-induced
diabetes mellitus.
Micropuncture of Munich-Wistar rats suggests that a reduction of intraglomerular pressure may be at least partially responsible for such an effect.