Online feedback-controlled renal constant infusion clearances in rats

Area of Science:

• Pharmacology and Toxicology
• Renal Physiology
• Biomedical Engineering

Background:

• Constant infusion clearance techniques are the gold standard for glomerular filtration rate (GFR) assessment.
• Exogenous renal markers are crucial for these GFR measurements.
• Current methods can be labor-intensive and require frequent sample collection.

Purpose of the Study:

• To develop and validate a real-time, automated closed-loop system for constant infusion clearance monitoring in rats.
• To optimize parameters for rapid achievement of steady-state conditions using a simulation tool.
• To enable precise, real-time monitoring and control of GFR measurements.

Main Methods:

• Development of a Matlab-based simulation tool to optimize infusion parameters.
• Implementation of a real-time feedback-regulated system using transcutaneous measurement of FITC-sinistrin.
• Validation in healthy and unilaterally nephrectomized rats, assessing plasma concentrations and GFR hourly.

Main Results:

• The transcutaneous FITC-sinistrin fluorescence signal accurately reflects plasma concentrations.
• The developed system precisely determines the onset of steady-state marker concentration.
• Real-time monitoring and control of steady-state conditions were achieved for several hours.

Conclusions:

• A novel, automated, real-time feedback system for constant infusion clearance was successfully developed and validated in rats.
• This method simplifies GFR assessment by minimizing sample requirements (no urine, one blood sample).
• The system allows for efficient and precise regulation and monitoring of GFR measurements.