Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h
Surajith N Wanasundara1, Michal J Wesolowski, Mark C Barnfield
1aDepartment of Medical Imaging, Royal University Hospital, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan bDepartment of Radiology, Memorial University of Newfoundland, Nuclear Medicine, The General Hospital, St. John's, Newfoundland and Labrador, Canada cThe Department of Medical Physics and Engineering, St. James's University Hospital, Leeds dNuclear Medicine Department, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield eNuclear Medicine Department, The Royal Free London NHS Foundation Trust, London, UK.
A new method using Tikhonov adaptively regularized gamma variate fitting (Tk-GV) accurately measures glomerular filtration rate (GFR) clearance with fewer samples. This simplified GFR testing reduces sampling time and improves patient tolerance.
Area of Science:
- Nephrology
- Nuclear Medicine
- Pharmacokinetics
Background:
- Glomerular filtration rate (GFR) is crucial for assessing kidney function.
- Current GFR measurement methods often require numerous, prolonged blood samples, which can be challenging for patients, especially children.
- There is a need for simplified, accurate, and precise GFR measurement techniques.
Purpose of the Study:
- To evaluate and compare two plasma concentration curve area methods for calculating GFR clearance (CL).
- To determine if reduced sampling times (4 hours with 4 samples) can maintain accuracy and precision compared to standard methods (8 hours with 9 samples).
Main Methods:
- Comparison of GFR clearance (CL) values derived from biexponential fitting [CL (E2)] and Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)].
- Analysis of 412 Tc-DTPA studies in 142 patients, primarily pediatric, with suspected fluid disturbances.
- Evaluation of 4 versus 8-hour time samplings (4 samples vs. 9 samples).
Main Results:
- CL (Tk-GV) using 4 samples/4h and 9 samples/8h showed accurate and precise agreement with the standard method (noncompartmental numerical integration [CL (NI)]).
- The biexponential fitting method [CL (E2)] significantly overestimated CL (NI) values by 4.9% (4 samples/4h) and 3.8% (9 samples/8h).
- CL (Tk-GV) demonstrated accuracy and precision comparable to the standard method with reduced sampling.
Conclusions:
- The biexponential fitting method [CL (E2)] is inaccurate and imprecise for GFR clearance calculation and should be replaced.
- The Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] method allows for a significant reduction in sampling time (from 8 to 4 hours) and sample number (from 9 to 4).
- CL (Tk-GV) offers a precise, accurate, simplified, and more tolerable method for GFR testing.
Related Concept Videos
Measurement of Bioavailability: Pharmacokinetic Methods
Clearance Models: Noncompartmental Models
The noncompartmental approach capitalizes on extensive sampling data, correlating the volume of distribution to systemic exposure and the administered dosage. This method enables...
One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance
In the one-compartment open model for intravenous (IV) bolus administration, clearance is estimated by dividing the elimination rate by the plasma drug concentration. This equation leverages the elimination rate constant and the apparent...
Noncompartmental Analysis: Miscellaneous Pharmacokinetic Parameters
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
Drug Elimination: The Concept of Clearance
Drug clearance is not limited to renal excretion but encompasses all organs involved in drug elimination,...
Renal Clearance
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...


