Repeated intravenous infusion of human apolipoprotein(a) kringle V is associated with reversible dose-dependent acute tubulointerstitial nephritis without affecting glomerular filtration function
| Autor: | Yong Keun Park, Hyun Kyung Yu, Ho Jeong Lee, Jin Hyung Ahn, Yeup Yoon, Sun Jin Kim, Jang Seong Kim |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Apolipoprotein B Renal function Angiogenesis Inhibitors Pharmacology Kidney Weight Gain Toxicology Blood Urea Nitrogen Rats Sprague-Dawley chemistry.chemical_compound Glomerular Filtration Barrier Internal medicine Toxicity Tests medicine Animals Infusions Intravenous Acute tubulointerstitial nephritis Pathological Blood urea nitrogen Apolipoproteins A Creatinine Dose-Response Relationship Drug biology business.industry Recovery of Function General Medicine Peptide Fragments Rats Angiogenesis inhibitor Clinical trial Endocrinology chemistry Area Under Curve Acute Disease biology.protein Nephritis Interstitial business Glomerular Filtration Rate |
| Zdroj: | Toxicology Letters. 212:298-306 |
| ISSN: | 0378-4274 |
| Popis: | Because anti-angiogenic agents have shown various toxicities in clinical applications, the determination of their toxicities and their reversibility is important in the design of clinical trials. This study was performed to investigate the potential toxicities of an angiogenesis inhibitor, apolipoprotein(a) (Apo(a)) kringle V (rhLK8) in rats. Rats administered an intravenous (IV) bolus injection of rhLK8 (200 mg/kg) for 7 days showed significant increases in serum blood urea nitrogen (BUN), creatinine and the BUN/creatinine ratio, which was compatible with acute tubulointerstitial nephritis (TIN) in pathological examination. Because anti-angiogenic therapies are usually based on long-term treatment strategies, rats were administered 200 mg/kg/day of rhLK8 by intravenous infusion for 28 days. Rats receiving 200 mg/kg of rhLK8 showed abnormal serological and histologic findings, but their levels returned to within normal ranges 2 weeks after the cessation of administration. The creatinine clearance rate (CCr) was not affected by rhLK8 treatment. Collectively, our data indicate that the intravenous infusion of rhLK8 at therapeutic doses may induce renal toxicities, such as acute TIN, but these toxicities are clinically tolerable and reversible with close monitoring and a recovery period. |
| Databáze: | OpenAIRE |
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