Phosphate restriction reduces proteinuria of the uninephrectomized, diabetic rat.
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.
Harris
D C
DC
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Falk
S A
SA
Conger
J D
JD
Hammond
W S
WS
Schrier
R W
RW
D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000652:urine*; D005919:Glomerular Filtration Rate; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D009392:Nephrectomy; D010710:Phosphates / Q000172:deficiency*; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D014655:Vascular Resistance
D010710:Phosphates; D000536:Aluminum Hydroxide; C007420:dihydroxyaluminum aminoacetate; D005998:Glycine