Evaluation of 10 Urinary Biomarkers for Renal Safety With 5 Nephrotoxicants in Nonhuman Primates
| Autor: | Frank D. Sistare, Sean P. Troth, Warren E. Glaab, Katerina Vlasakova |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Primates
Urinary system Physiology Lipocalin Toxicology Kidney Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lipocalin-2 medicine Animals Cystatin C Molecular Biology 030304 developmental biology 0303 health sciences Creatinine Retinol binding protein 4 biology Clusterin business.industry Cell Biology Acute Kidney Injury medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis biology.protein Biomarker (medicine) Cisplatin Gentamicins business Biomarkers |
| Zdroj: | Toxicologic pathology. 48(5) |
| ISSN: | 1533-1601 |
| Popis: | To date, there has been very little published data evaluating the performance of novel urinary kidney biomarkers in nonhuman primates (NHPs). To assess the biomarker performance and characterize the corresponding histomorphologic patterns of tubular renal injury in the NHP, several studies were conducted using mechanistically diverse nephrotoxicants including cefpirome, cisplatin, naproxen, cyclosporine, and a combination of gentamicin with everninomicin. An evaluation of 10 urinary biomarkers (albumin, clusterin, cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, N-acetyl-β-D-glucosaminidase, osteopontin, retinol binding protein 4 and total protein) was performed on urine collected from these studies. Each of these 5 treatments resulted in kidney proximal tubule injury of various severities. Histomorphologic features observed following treatment were generally consistent with analogous drug-induced changes in humans described in the literature. Most of the analyzed biomarkers were able to detect the injury earlier and with greater sensitivity than blood urea nitrogen and serum creatinine. Across all studies, KIM-1 and clusterin showed the highest overall performance. Differences in the patterns of biomarker responsiveness were noted among certain studies that may be informing tubular injury severity and recovery potential, underlying histopathologic processes, and prognosis. These findings demonstrate the utility of urinary kidney translational safety biomarkers in NHPs and provide additional supporting evidence for translating these biomarkers for use in clinical trial settings to further ensure patient safety. |
| Databáze: | OpenAIRE |
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