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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 C b (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-0.15mL/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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Population mean GFR is lower in older age, but it is unknown whether healthy aging is associated with preserved rather than lower GFR in some individuals., Methods: We investigated the cross-sectional association between measured GFR, age, and health in persons aged 50-97 years in the general population through a meta-analysis of iohexol clearance measurements in three large European population-based cohorts. We defined a healthy person as having no major chronic disease or risk factors for CKD and all others as unhealthy. We used a generalized additive model to study GFR distribution by age according to health status., Results: There were 935 (22%) GFR measurements in persons who were healthy and 3274 (78%) in persons who were unhealthy. The mean GFR was lower in older age by -0.72 ml/min per 1.73 m 2 per year (95% confidence interval [95% CI], -0.96 to -0.48) for men who were healthy versus -1.03 ml/min per 1.73 m 2 per year (95% CI, -1.25 to -0.80) for men who were unhealthy, and by -0.92 ml/min per 1.73 m 2 per year (95% CI, -1.14 to -0.70) for women who were healthy versus -1.22 ml/min per 1.73 m 2 per year (95% CI, -1.43 to -1.02) for women who were unhealthy. For healthy and unhealthy people of both sexes, both the 97.5th and 2.5th GFR percentiles exhibited a negative linear association with age., Conclusions: Healthy aging is associated with a higher mean GFR compared with unhealthy aging. However, both the mean and 97.5 percentiles of the GFR distribution are lower in older persons who are healthy than in middle-aged persons who are healthy. This suggests that healthy aging is not associated with preserved GFR in old age., (Copyright © 2020 by the American Society of Nephrology.)