Abstract
Otago BMLSc student research project abstract.
Objectives: Within New Zealand, chronic kidney disease poses a large burden on the healthcare system and is associated with significant treatment costs. Reducing the incidence or severity of kidney disease will substantially reduce kidneyrelated mortality. Previous research found that the drug amiloride down-regulated fibrosis in three models of kidney fibrosis (lithium-, folic acid-, and adenine- induced). However, amiloride’s effects on kidney damage and oxidative stress pathways remain unclear. This study aimed to extend the analysis and understanding of amiloride’s potential benefits.
Methods: Immunohistochemistry for NGAL as a marker of kidney damage, and NRF2 as a marker of protection against oxidative damage was performed on 56 rat kidney sections from the adenine and folic acid studies. NGAL expression was quantified using ImageScope analysis software, while NRF2 analysis is ongoing.
Results: Statistical analysis of NGAL expression revealed a significant increase in the cortex and medulla of adenine-treated rats compared to controls, with no statistical difference between the adenine and adenine plus amiloride treatment groups. No statistically significant differences were observed between folic acid treated groups in the cortex and medulla. Neutrophil counts were also significantly increased in the adenine group compared to controls, with no significant differences between adenine and adenine plus amiloride groups or between the folic acid groups.
Conclusion: These findings suggest that amiloride does not significantly reduce NGAL tissue expression. This may reflect the increased recruitment of neutrophils that were evident as opposed to lack of modification of kidney injury. Further studies into amiloride’s method of action in reducing kidney inflammation and fibrosis are underway. This could reveal novel therapeutic targets for kidney disease, addressing a critical unmet need in kidney disease treatment.