Comparability of Plasma Iohexol Clearance Across Population-Based Cohorts

Bjørn O. Eriksen, Elke Schaeffner, Toralf Melsom, Natalie Ebert, Markus van der Giet, Vilmundur Gudnason, Olafur S. Indridasson, Amy B. Karger, Andrew S. Levey, Mirjam Schuchardt, Liv K. Sørensen, Runolfur Palsson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Rationale & Objective: Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and clinical trials despite several important and well-known limitations. Plasma iohexol clearance has been proposed as an inexpensive method for measuring GFR that could replace estimated GFR in many research projects. However, lack of standardization for iohexol assays and the use of different protocols such as single- and multiple-sample methods could potentially hamper comparisons across studies. We compared iohexol assays and GFR measurement protocols in 3 population-based European cohorts. Study Design: Cross-sectional investigation. Setting & Participants: Participants in the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney; n = 805), the Berlin Initiative Study (BIS, n = 570), and the Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU; n = 1,324). Tests Compared: High-performance liquid chromatography analyses of iohexol. Plasma iohexol clearance calculated using single- versus multiple-sample protocols. Outcomes: Measures of agreement between methods. Results: Frozen samples from the 3 studies were obtained and iohexol concentrations were remeasured in the laboratory at the University Hospital of North Norway. Lin's concordance correlation coefficient ρ was >0.96 and Cb (accuracy) was >0.99 for remeasured versus original serum iohexol concentrations in all 3 cohorts, and Passing-Bablok regression did not find differences between measurements, except for a slope of 1.025 (95% CI, 1.006-1.046) for the log-transformed AGES-Kidney measurements. The multiple-sample iohexol clearance measurements in AGES-Kidney and BIS were compared with single-sample GFRs derived from the same iohexol measurements. Mean bias for multiple-sample relative to single-sample GFRs in AGES-Kidney and BIS were −0.25 and −0.15 mL/min, and 99% and 97% of absolute differences were within 10% of the multiple-sample result, respectively. Limitations: Lack of comparison with an independent gold-standard method. Conclusions: Agreement between the iohexol assays and clearance protocols in the 3 investigated cohorts was substantial. Our findings indicate that plasma iohexol clearance measurements can be compared across these studies.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume76
Issue number1
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
Dr Schaeffner has received honoraria from Siemens Healthcare and Fresenius Medical Care for giving a lecture on kidney function assessment and from Fresenius Kabi for providing lectures and chairing a workshop on critiquing the literature. Dr Karger has received grant funding for collaborations with Siemens Healthcare Diagnostics. Dr Ebert has received honoraria from Siemens Healthineers. The remaining authors declare that they have no relevant financial interests.

Funding Information:
Bj?rn O. Eriksen, MD, PhD, Elke Schaeffner, MD, MSc, Toralf Melsom, MD, PhD, Natalie Ebert, MD, MPH, Markus van der Giet, MD, Vilmundur Gudnason, MD, PhD, Olafur S. Indridasson, MD, MHS, Amy B. Karger, MD, PhD, Andrew S. Levey, MD, Mirjam Schuchardt, PhD, Liv K. S?rensen, BS, and Runolfur Palsson, MD. Development of study concept and design: BOE, ES, NE, RP, OSI, TM; acquisition, analysis or interpretation of data: BOE, ES, NE, RP, OSI, TM, MG, VG, ASL, LKS, ABK, MS; statistical analysis: BOE. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. AGES-Kidney was supported by a grant from National Institutes of Health, United States (R01 DK082447), a contract from the National Institute on Aging, United States (N01-AG-1-2100), Hjartavernd, Iceland (Icelandic Heart Association), and the Icelandic Parliament (Althingi). The Icelandic Heart Association provided support for data collection. BIS measurements were funded by the KfH-Foundation of Preventive Medicine, Germany and the Dr. Werner Jackst?dt Foundation, Germany. RENIS-FU was funded by the Northern Norway Regional Health Authority and supported by a grant from Boehringer-Ingelheim, Germany. The funding sources did not have any role in study design, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. Dr Schaeffner has received honoraria from Siemens Healthcare and Fresenius Medical Care for giving a lecture on kidney function assessment and from Fresenius Kabi for providing lectures and chairing a workshop on critiquing the literature. Dr Karger has received grant funding for collaborations with Siemens Healthcare Diagnostics. Dr Ebert has received honoraria from Siemens Healthineers. The remaining authors declare that they have no relevant financial interests. We thank all participants in the AGES-Kidney, BIS, and RENIS-FU cohorts for their contributions to this investigation. Received April 24, 2019. Evaluated by 4 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form October 5, 2019. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.

Funding Information:
AGES-Kidney was supported by a grant from National Institutes of Health, United States ( R01 DK082447 ), a contract from the National Institute on Aging, United States ( N01-AG-1-2100 ), Hjartavernd, Iceland (Icelandic Heart Association), and the Icelandic Parliament (Althingi). The Icelandic Heart Association provided support for data collection. BIS measurements were funded by the KfH-Foundation of Preventive Medicine, Germany and the Dr. Werner Jackstädt Foundation, Germany. RENIS-FU was funded by the Northern Norway Regional Health Authority and supported by a grant from Boehringer-Ingelheim, Germany . The funding sources did not have any role in study design, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.

Publisher Copyright:
© 2019 The Authors

Keywords

  • Renal clearance
  • accuracy
  • agreement
  • concordance correlation
  • glomerular filtration rate (GFR)
  • iohexol
  • kidney function tests
  • measured GFR
  • measurement error
  • multiple-sample
  • single-sample

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