Dataset Information

Measurement of renal functional response using iohexol clearance-a study of different outpatient procedures.

ABSTRACT:

Background

Glomerular filtration rate (GFR) increases after a heavy protein load; an increase termed renal functional response (RFR). Decreased RFR could be a marker of early kidney damage, but published methods are cumbersome in the outpatient setting. The present study investigates the use of iohexol clearance to measure RFR in outpatients using both one- and two-sample methods.

Methods

Fourteen healthy volunteers with a mean?±?SD age of 42?±?12?years were included (six males and eight females). GFR was measured using plasma iohexol clearance with one- and two-sample methodologies. Four measurements in each individual were performed: one baseline test and three protein loading tests containing 80 g protein (commercially available protein supplementations from Myo Nutrition and Proteinfabrikken and 350 g chicken breast). RFR was calculated as percentage increase in GFR from the baseline test.

Results

Mean RFR was 11.4?±?5.4% and 12.1?±?6.4% using one- and two-sample methods, respectively. The three different protein loads resulted in similar mean RFR but there was considerable intra-individual variability. One- and two-sample methods for measurement of RFR showed similar results with near-identical means, but there was some intra-individual variation that was similar for different protein loads. The overall 95% limit of agreement between one- and two-sample methods for calculating RFR was -8.7 to 7.3.

Conclusions

RFR can be investigated using plasma iohexol clearance in an outpatient setting. Protocols using commercially available protein supplementation showed a mean RFR of about 12%. One- and two-sample methods for measuring RFR yield similar results.

SUBMITTER: Lillas BS

PROVIDER: S-EPMC7857819 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Measurement of renal functional response using iohexol clearance-a study of different outpatient procedures.

Lillås Bjørn Steinar BS Tøndel Camilla C Gjerde Anna A Vikse Bjørn Egil BE

Clinical kidney journal 20191126 1

<h4>Background</h4>Glomerular filtration rate (GFR) increases after a heavy protein load; an increase termed renal functional response (RFR). Decreased RFR could be a marker of early kidney damage, but published methods are cumbersome in the outpatient setting. The present study investigates the use of iohexol clearance to measure RFR in outpatients using both one- and two-sample methods.<h4>Methods</h4>Fourteen healthy volunteers with a mean ± SD age of 42 ± 12 years were included (six males an ...[more]

PMID: 33564417

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Project description:BackgroundIohexol plasma clearance-based glomerular filtration rate (GFR) determination provides an accurate method for renal function evaluation. This technique is increasingly advocated for clinical situations that dictate highly accurate renal function assessment, as an alternative to conventional serum creatinine-based methods with limited accuracy or poor feasibility. In the renal transplantation setting, this particularly applies to living renal transplant donor eligibility screening, renal transplant function monitoring and research purposes. The dependency of current iohexol GFR estimation techniques on extensive sampling, however, has limited its clinical application. We developed a population pharmacokinetic model and limited sampling schedules, implemented in the online InsightRX precision dosing platform, to facilitate pragmatic iohexol GFR assessment.MethodsIohexol concentrations (n = 587) drawn 5 min to 4 h after administration were available from 67 renal transplant recipients and 41 living renal transplant donor candidates with measured iohexol GFRs of 27-117 mL/min/1.73 m2. These were split into a model development (n = 72) cohort and an internal validation (n = 36) cohort. External validation was performed with 1040 iohexol concentrations from 268 renal transplant recipients drawn between 5 min and 4 h after administration, and extended iohexol curves up to 24 h from 11 random patients with impaired renal function. Limited sampling schedules based on one to four blood draws within 4 h after iohexol administration were evaluated in terms of bias and imprecision, using the mean relative prediction error and mean absolute relative prediction error. The total deviation index and percentage of limited sampling schedule-based GFR predictions within ± 10% of those of the full model (P10) were assessed to aid interpretation.ResultsIohexol pharmacokinetics was best described with a two-compartmental first-order elimination model, allometrically scaled to fat-free mass, with patient type as a covariate on clearance and the central distribution volume. Model validity was confirmed during the internal and external validation. Various limited sampling schedules based on three to four blood draws within 4 h showed excellent predictive performance (mean relative prediction error < ± 0.5%, mean absolute relative prediction error < 3.5%, total deviation index < 5.5%, P10 > 97%). The best limited sampling schedules based on three to four blood draws within 3 h showed reduced predictive performance (mean relative prediction error < ± 0.75%, mean absolute relative prediction error < 5.5%, total deviation index < 9.5%, P10 ≥ 85%), but may be considered for their enhanced clinical feasibility when deemed justified.ConclusionsOur online pharmacometric tool provides an accurate, pragmatic, and ready-to-use technique for measured GFR-based renal function evaluation for clinical situations where conventional methods lack accuracy or show limited feasibility. Additional adaptation and validation of our model and limited sampling schedules for renal transplant recipients with GFRs below 30 mL/min is warranted before considering this technique in these patients.

Project description:BackgroundMeasuring 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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 registrationThe "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).

Dataset Information

Measurement of renal functional response using iohexol clearance-a study of different outpatient procedures.

Background

Methods

Results

Conclusions

Publications

Measurement of renal functional response using iohexol clearance-a study of different outpatient procedures.

Similar Datasets

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