Kidney Injury Monitoring in Tobramycin-Treated Rhesus Monkeys: Supplementing Urinary Kidney Biomarkers With Kidney Biopsy Gene Expression Profiling
| Autor: | Stephanie Born, Yi-Zhong Gu, Larry Handt, Vasudevan Bakthavatchalu, Katerina Vlasakova, Frank D. Sistare, Guillermo Fernandez, Warren E. Glaab, Roger Smith |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Pathology Biopsy Urinary system Kidney Toxicology Pathology and Forensic Medicine chemistry.chemical_compound medicine Animals Osteopontin Molecular Biology Blood urea nitrogen Creatinine medicine.diagnostic_test Clusterin biology urogenital system business.industry Gene Expression Profiling Cell Biology Acute Kidney Injury Macaca mulatta medicine.anatomical_structure chemistry Tobramycin biology.protein Histopathology business Biomarkers |
| Zdroj: | Toxicologic Pathology. 50:35-46 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/01926233211049171 |
| Popis: | Kidney biopsies are used sparingly to diagnose kidney injury in the clinic. Here we have conducted a small exploratory study to directly compare the low-grade kidney injury monitoring performance of serum safety biomarkers, novel urine safety biomarkers, microscopic histopathology and targeted gene expression alterations in kidney biopsy specimens in rhesus monkeys treated with tobramycin. Targeted gene expression increases were observed in the kidney biopsy samples and whole kidney sections for kidney injury molecule 1 ( KIM-1), clusterin ( CLU), osteopontin ( OPN) messenger RNA transcripts. In addition, increases of the urinary kidney safety protein biomarkers including KIM-1, CLU, OPN were also observed. These increases in gene expression and urinary protein end point were in concordance with the eventual low-grade kidney lesions seen in terminal tissue sections. In contrast, conventional serum biomarkers blood urea nitrogen and serum creatinine were not as sensitive in monitoring kidney injury. Although these data do not support routinely adding kidney biopsies to regular toxicology studies, they provide evidence on the value and limitations of incorporating gene expression profiling on kidney biopsy specimens, further underscore the value of urinary kidney safety biomarkers for improved low-grade kidney injury monitoring, and open the door for future definitive studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|