# Ultrastructural and Immunohistochemical Study on the Nephrotoxicity Following Intravitreal Administration of the Antifungal Agents Voriconazole and Micafungin in New Zealand White Rabbits

## TL;DR

This study investigates kidney damage in rabbits after eye injections of antifungal drugs voriconazole and micafungin.

## Contribution

The study reveals potential nephrotoxic effects of intravitreal antifungal agents in rabbits, suggesting clinical relevance for humans.

## Key findings

- Ultrastructural kidney damage was observed, especially in proximal tubules.
- Increased expression of EGFR and IL-6 markers was found with drug administration.
- Findings suggest a need to study reversibility and adjust dosing to prevent kidney toxicity.

## Abstract

The aim of the present study is to examine the possibility of nephrotoxicity following the intravitreal injection of the antifungal agents voriconazole and micafungin. Μale and female New Zealand white rabbits were divided into the control group C that received no medication and the study groups that underwent either one or two intravitreal injections of voriconazole or micafungin solution, respectively, or one co-administration of the two agents. Euthanasia was performed ten days after the last intravitreal administration, and kidney tissue samples were obtained and prepared for electron microscopy study, as well as immunohistochemical study for EGFR and IL-6 markers. Ultrastructural alterations of the renal tissue were found in places of limited extent, more evident at the level of the proximal tubules. The expression of the two markers was positive, especially in the double and the combined administration of the two drugs, both in the renal corpuscle and the tubules. The finding of the aforementioned histological lesions triggers the need for an additional study of the effect of the specific drugs on the kidney to establish whether these alterations are reversible or not. Redesigning the dosage regimen during intravitreal administration of these agents could be a future therapeutic goal to prevent potential nephrotoxicity. The intravitreal concentrations used in rabbits, particularly for voriconazole, closely approximate those used in humans, supporting the clinical relevance of the findings.