Development of a nonisotopic capillary electrophoresis‐based method for measuring glomerular filtration rate

Abstract

The conditions for quantitative measurement of nonisotopic iothalamate meglumine (Conray) in urine and plasma by capillary zone electrophoresis (CE) have been developed. The impetus for developing this methodology was to replace the traditional [125I]iothalamate glomerular filtration rate (GFR) marker assay, a routine tool in the measurement of kidney function. This new approach for measuring kidney function is attractive since it avoids the cost of administration of radioisotopic compounds to patients, as well as the cost associated with purchase and disposal of isotopic compounds and contaminated samples. The concentration of iothalamate in urine and plasma determined by CE can be used directly to calculate GFR. The GFR in patients injected with [125I]iothalamate and nonisotopic iothalamate simultaneously showed an excellent correlation (0.998) with between-day coefficient of variation of 2.30% and a recovery of 102% and 98%, respectively, when added to urine and plasma. Interference from drugs and other urinary compounds is eliminated with this method. Collectively, this study has shown that CE is a cost-effective alternative to the current methodology for measuring GFR.

Capillary Electrophoresis Method to Measure p-Aminohippuric Acid in Urine and Plasma for the Assessment of Renal Plasma Flow

“…High-sensitivity methods that are capable of reliably measuring CRP concentrations Յ0.15 mg/L (approximately the first and second percentiles of CRP distribution in healthy adults) have, therefore, been developed (7,8 ). Furthermore, an algorithm for risk assessment of future coronary events that combines both CRP concentration and total cholesterol:HDL-cholesterol ratio has been proposed (9 ). According to this algorithm, an individual's risk can be estimated with use of quintiles of CRP and lipids derived from ongoing population-based surveys.…”

“…Measurement of PAH in urine and plasma by HPLC has been described (4 -7 ), but it requires relatively large sample volumes and time-consuming extraction procedures. We recently found that capillary electrophoresis (CE) is an efficient, inexpensive, and reliable method for measurement of the nonradiolabeled iothalamate in urine and plasma samples for the assessment of glomerular filtration rate (8,9 ). Analysis by CE is analytically faster than standard HPLC or colorimetric assays, requires less reagent preparation and smaller sample size, minimizes drug interferences, and improves test turnaround time.…”

Iothalamate Quantification by Tandem Mass Spectrometry to Measure Glomerular Filtration Rate

“…GFR can be more precisely and accurately measured using exogenous compounds that are freely cleared by the kidney. Iothalamate is a radiopaque imaging media that has been used extensively in research and clinical practice for GFR determination (5)(6)(7)(8). 125 I-labeled iothalamate has been used for GFR measurement (9,10 ).…”

“…To avoid the use of radioactive materials, laboratory methods have been developed to quantify nonradioactive iothalamate using HPLC (5,6,(11)(12)(13) or capillary electrophoresis (CE) (7,8 ) coupled with ultraviolet (UV) detection systems. The HPLC-UV methods require long run times, limiting sample throughput, and the CE-UV methods can be susceptible to interference (7,8 ).…”

“…To minimize interference with iothalamate quantification, the previously reported CE-UV method used in our laboratory (7,8 ) has since been modified to run in reverse polarity. Interferences are still encountered in approximately 1% of patient samples, however.…”