Dataset Information

Iohexol plasma clearance for measuring glomerular filtration rate: effect of different ways to calculate the area under the curve.

ABSTRACT:

Background

Measuring glomerular filtration rate (GFR) using iohexol plasma clearance has been proposed as the preferred way for GFR determination. The extended multiple-sample protocol is based on fitting the full concentration-time decay-curve, and from the obtained fit-parameters, the area under the curve (AUC) and GFR (the injected dose divided by the AUC) were calculated. The goal of the current study is to evaluate the impact of different fitting procedures on the precision of GFR-results obtained from the full concentration-time curve, and compare these results with those obtained with simplified multiple-samples and single-sample protocols.

Methods

The concentration-time curves of 8 samples at times 30, 60, 90, 120, 150, 180, 240 and 300 min after bolus injection of iohexol of 570 adults, aged 70+, from the Berlin Initiative Study (BIS), were analysed. The fit-parameters for the two-compartment model (double-exponential decay curve), and from these, the AUC and GFR were obtained with 8 different fitting procedures.

Results

The two-compartmental non-linear least squares fitting procedure showed the best accuracy (541 out of 570 reported GFR-results were within 5% of the majority of the 8 fitting methods). The two-compartmental slope-intercept fitting procedure was not always applicable and the non-compartmental fitting procedures did not always allow to calculate the GFR. All correction formulas for the simplified late multiple-samples methods showed acceptable accuracy and precision with a preference for Ng's correction formula (Lin's CCC = 0.992, bias = 0.5 ± 2.5). Jacobsson's iterative method was the best one-sample method, with Lin's CCC = 0.983 and bias = - 0.6 ± 3.4.

Conclusion

The fitting procedure has an important impact on the precision of the calculated AUC and GFR. The simplified late-sample protocols and one-sample methods did not suffer from fitting problems and showed acceptable equivalence when compared to the full compartment GFR-results.

Trial registration

The "Berlin Initiative Study" is officially registered with the German Register for Clinical Studies ("Deutschen Register Klinischer Studien"(DRKS)) under registration number DRKS00017058 , since April 12, 2019, and it is also visible on the WHO clinical trials registry platform (within the next 4 weeks after the registration date).

SUBMITTER: Pottel H

PROVIDER: S-EPMC8101203 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThere is currently no accurate method of measuring glomerular filtration rate (GFR) during acute kidney injury (AKI). Knowledge of how much GFR varies in stable subjects is necessary before changes in GFR can be attributed to AKI. We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI. The aims of this crossover trial were to establish accuracy and precision of a continuous infusion of low dose Iohexol (CILDI) and variation in GFR in stable volunteers over a range of estimated GFR (23-138 mL/min/1.73 m(2)).MethodsWe randomised 17 volunteers to GFR measurement by plasma clearance (PC) and renal clearance (RC) of either a single bolus of Iohexol (SBI; routine method), or of a continuous infusion of low dose Iohexol (CILDI; experimental method) at 0.5 mL/h for 12 h. GFR was measured by the alternative method after a washout period (4-28 days). Iohexol concentration was measured by high performance liquid chromatography/electrospray tandem mass spectrometry and time to steady state concentration (Css) determined.ResultsMean PC was 76.7 ± 28.5 mL/min/1.73 m(2) (SBI), and 78.9 ± 28.6 mL/min/1.73 m(2) (CILDI), p = 0.82. No crossover effects occurred (p = 0.85). Correlation (r) between the methods was 0.98 (p < 0.0001). Bias was 2.2 mL/min/1.73 m(2) (limits of agreement -8.2 to 12.6 mL/min/1.73 m(2)) for CILDI. PC overestimated RC by 7.1 ± 7.3 mL/min/1.73 m(2). Mean intra-individual variation in GFR (CILDI) was 10.3% (p < 0.003). Mean ± SD Css was 172 ± 185 min.ConclusionWe hypothesise that changes in GFR >10.3% depict evolving AKI. If this were applicable to AKI, this is less than the 50% change in serum creatinine currently required to define AKI. CILDI is now ready for testing in patients with AKI.Trial registrationThis trial was registered with the European Union Clinical Trials Register ( https://www.clinicaltrialsregister.eu/ ), registration number: 2010-019933-89 .