Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate.

Abstract

Renal clearance of inulin is the best available indicator of GFR but cannot be used routinely for clinical purposes and is also difficult to perform for clinical investigation when repeated measurements are required. The aim of this study was to find a reliable alternative to inulin clearance that would allow one to avoid the use of radioactivity and problems related to the continuous infusion of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per 1.73 m2) underwent simultaneous measurements of renal clearance of inulin and plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood samples were drawn up to 600 min after the administration. Iohexol concentrations (by HPLC) were analyzed by a two-compartment, open-model system. A highly significant correlation between the plasma clearance of iohexol and the renal clearance of inulin over a wide range of GFR values was found. By analyzing the data with a simplified method that uses a one-compartment model corrected with the Bröchner-Mortensen formula, an excellent correlation with the inulin clearance was also observed. When only patients with moderate to severe renal failure were considered, a significant correlation between the two methods was found. A further comparison between GFR determined with iohexol and iopromide, a new low-osmolarity, low-viscosity contrast medium, was also performed in a subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Measured Glomerular Filtration Rate: The Query for a Workable Golden Standard Technique

“…Analysis of the non-ionic contrast medium iohexol can be performed with several methods: liquid chromatography-tandem mass spectrometry (LC-MS/MS) [8], highperformance liquid chromatography-ultraviolet detection (HPLC-UV) [51,52], and X-ray fluorescence [8]. In an aqueous solution, iohexol exists as a mixture of isomers, which slowly interconvert and gradually equilibrate to an isomeric ratio [53].…”

“…These differences in the reported plasma iohexol clearances might be explained by divergent registered concentrations by LC-MS/MS vs. HPLC-UV, related to a variable presence of endo-and exo-isomers of iohexol [27]. In the majority of HPLC-UV measurement procedures, separation and quantification are only based on the major (exo-iohexol) isomeric peak [26,51,57]. In contrast to HPLC-UV, LC-MS/MS measurement procedures typically do not separate iohexol isomers and quantify all forms of iohexol in one single integration event.…”

“…The plasma disappearance curve after a single, well-defined dose after a single injection of radioactive tracers such as 51 Cr-EDTA, 99m Tc-DTPA, and 125 I-iothalamate can be used to measure GFR [60]. The use of 51 Cr-EDTA is associated with a lower workload for preparation and reference activities as the calibration reference curve is stable for several weeks with a long half-life (27.7 days), compared to only 6 h for 99m Tc-DTPA [61] and 3.2 h for 125 I-iothalamate [62].…”

“…Criteria for reliable exogenous GFR markers are the following: water-soluble, not bound to proteins, only excreted by the kidneys, 100% filtered through the glomerulus in subjects with a normal kidney function, and neither secreted nor absorbed by the kidney tubules. Several exogenous markers have been evaluated for this purpose including inulin, 51 Cr-ethylenediamine tetraacetic acid ( 51 Cr-EDTA), 99m Tc-diethylenetriamine pentaacetic acid ( 99m Tc-DTPA), 125 I-iothalamate, and some non-isotopic "cold" markers (iothalamate and iohexol) [7,8]. This opinion paper provides an overview of these exogenous mGFR markers, along with their limitations, in chronic stable individuals.…”

The correlation between kidney volume and measured glomerular filtration rate in an Asian ADPKD population: a prospective cohort study

“…The authors in previous studies have suggested that in early stages of ADPKD, the variability in serum creatinine levels may be explained by creatinine production related to muscle mass or protein intake rather than glomerular filtration [ 22 ]. Therefore, direct measurements of GFR by gold-standard techniques depended on the use of exogenous markers such as inulin, iohexol or radio-labeled tracers, which would be essential in order to assess the accuracy of GFR decline in the studied population [ 23 – 25 ].…”