A method for estimating the glomerular filtration rate in conscious monkeys

Area of Science:

• Pharmacokinetics and Toxicology
• Renal Physiology
• Non-human Primate Models

Background:

• Estimating glomerular filtration rate (GFR) in non-human primates is crucial for toxicological research.
• Current methods for GFR assessment can be invasive or require multiple samples, increasing animal stress.
• Developing a practical and reliable GFR estimation method in conscious monkeys is needed.

Purpose of the Study:

• To establish a practical method for estimating GFR in conscious cynomolgus monkeys.
• To validate a single-blood-sample method using the radiographic contrast agent iodixanol.
• To compare iodixanol-based GFR estimates with traditional methods.

Main Methods:

• Coadministration of iodixanol and inulin as tracers in male cynomolgus monkeys.
• Bolus injection followed by blood collection at 60, 90, and 120 minutes.
• Development of a single-blood-sample GFR estimation equation based on Jacobsson's formula using iodixanol data.

Main Results:

• The single-sample iodixanol method showed agreement with multi-sample inulin and iodixanol GFR measurements.
• Serum creatinine increased when GFR decreased by over 60% from baseline.
• Serum blood urea nitrogen levels fluctuated without a clear correlation with GFR changes.

Conclusions:

• The single-blood-sample method with iodixanol is a practical tool for estimating monkey GFR.
• This method is suitable for toxicological research settings, minimizing animal suffering.
• Iodixanol offers a viable alternative for GFR assessment in non-human primates.