Effect of Low-Protein Diet on Glomerular Changes in ddY Mice; A Spontaneous Animal Model of IgA Nephropathy

Yasuhiko Tomino, MD, Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113 (Japan) Dear Sir, Long-term dietary protein restriction is generally considered to reduce the levels of urinary protein and ameliorate the glomerular injuries in patients with various glomeru-lonephritides. We usually start dietary protein restriction after the definite diagnosis, although restriction from an early stage might show a good prognosis in such diseases. The authors reported that the ddY mouse strain can serve as a spontaneous animal model for IgA nephropathy [1, 2]. Marked depositions of IgA and C3 in glo-meruli and glomerular mesangial expansion were observed in the ddY mice after 40 weeks of age [1]. We attempted to compare the glomerular changes between the low-protein and the high-protein diets in ddY mice. Twenty ddY mice were fed a standard diet containing 22% protein until 40 weeks of age. These ddY mice were divided into two diet groups, i.e. low protein (6%) and high protein (50%). ddY mice of both groups were sacrificed at 70 weeks of age. Urinary protein was measured every 2 weeks according to the method of Knight et al. [3]. Renal sections stained with hematoxylin and eosin, and periodic acid-Schiff were examined by light microscopy. Renal cryostat sections were stained with FITClabelled goat anti-mouse IgA, IgG, IgM and C3 antisera at room temperature for 45 min. Type IV and I collagens, ñbronectin and laminin were also stained. The sections were examined using a Fig. 1. a Glomerular enlargement and mesangial expansion were observed in the high-protein diet ddY mouse. PAS. × 400. b These light-microscopic findings were improved in the lowprotein diet mouse. PAS. × 400. c Glomerular deposition of IgA was marked in the high-protein diet ddY mouse. × 400. d The intensity of glomerular IgA deposition was decreased in the lowprotein diet mouse. × 400. KAIIGER E-Mail karger@karger.ch Fax+ 41 61 306 12 34 © 1996 S. KargerAG, Basel 0028-2766/96/0722-0333S8.00/0