Chronic Administration of Methylmalonic Acid (MMA) to Rats Causes Proteinuria and Renal Tubular Injury • 1815

摘要: Children with methylmalonic acidemia frequently develop chronic renal insufficiency, for reasons unknown. We administered MMA chronicaally to rats test the hypothesis that is nephrotoxic. Methods: 3-wk-old Sprague-Dawley received (pH 7.2-7.4), 20mg/100g BW daily by SQ injection X 6 wks (N=6), then in drinking water (40mg/100g BW/day) more wks. Two from outset (20mg/100g BW/day 4 wks, 40mg/100g 8 wks). Five saline injections twice Urine and blood were collected every 2 Renal biopsy was performed at necropsy 12 Urinary measured stable isotope dilution gas chromatography- mass spectometry. Results: MMA-treated controls similar food intake, weight gain, serum creatinine BUN. or oral produced high urinary levels (e.g., 1646 μM/mM (mean), vs. 8.26 controls). Six of had proteinuria, first detected thereafter increased (Table). After MMA, glomeruli appeared normal but tubules proteinuric variably dilated (especially medulla) proteinaceous casts flattened epithelium. By EM, tubular epithelium showed variable mitochondrial swelling disorganization cristae, smooth endoplasmic reticulum, dilatation basolateral intercellular spaces, secondary lysosomes than controls. Conclusions: Chronic administration causes injury, which histologically appears predominantly affect epithelial cells. These findings suggest insufficiency associated results nephrotoxicity MMA.