Effects of lysine-induced acute renal failure in dogs.
This study investigates the effects of lysine-induced acute renal failure. Female dogs received a lysine hydrochloride (lysine) of 4500 mg/kg/day (3.75 ml/kg/hr) for 3 consecutive days. The dogs were observed for clinical signs. Body weights were recorded, food consumption and water consumption calculated, and urinalysis and blood biochemistry were performed daily. Plasma samples for amino acid determinations were obtained from all dogs, which were necropsied on Day 3. Histopathological examinations were done on all test animals. Compound-related findings include the following. Blood biochemistry results showed increases in ammonia, blood urea nitrogen, blood urea nitrogen/creatinine ratio, and creatinine. Urinary changes consisted of increases in urine volume, total protein, albumin, gamma-glutamyl transpeptidase, and N-acetyl-beta-D-glucosaminidase. In addition, macroscopic findings consisted of pale, congested capsule; microscopic findings consisted of hypertrophy of proximal convoluted tubule (mainly S1 segment), and degeneration/desquamation of urinary tubule (mainly S3 segment with hyaline casts) in the kidney. From these findings, it can be concluded that lysine is nephrotoxic in dogs. Nephrotoxicity of lysine may relate to direct tubular toxicity and to tubular obstruction.
Asanuma
Kentaro
K
Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizouka 412-8513, Japan. asanumaknt@chugai-pharm.co.jp
Adachi
Kenji
K
Sugimoto
Tetsuro
T
Chiba
Shuichi
S
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001774:Blood Chemical Analysis; D001837:Body Weights and Measures; D004285:Dogs; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000633:toxicity*; D016482:Urinalysis
D000596:Amino Acids; D008239:Lysine