Comparison of Early-Compartment Correction Equations for GFR Measurements (2020)

Measuring the glomerular filtration rate (GFR) remains indicated in specific patients and/or specific clinical contexts.1Delanaye P. Melsom T. Ebert N. et al.Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: why to measure glomerular filtration rate with iohexol?.Clin Kidney J. 2016; 9: 700-704Crossref PubMed Scopus (64) Google Scholar,2Agarwal R. Delanaye P. Glomerular filtration rate: when to measure and in which patients?.Nephrol Dial Transplant. 2019; 34: 2001-2007Crossref PubMed Scopus (14) Google Scholar For practical reasons, plasma clearances are preferred instead of urinary clearance. In most centers, the plasma clearance is calculated from exogenous marker concentrations obtained during the excretion phase (the second or slow GFR compartment), which is the most important for GFR determination. However, GFR is systematically overestimated because the part of the area under the curve (AUC) from the first (or early) compartment, which corresponds to the distribution of the marker in the body, is neglected. Because the AUC of the first compartment is not measured but estimated, it is prone to some imprecision, notably in high GFR ranges. Moreover, this overestimation can be corrected using various published mathematical models published by Chantler (C), Bröchner-Mortensen (BM), Fleming (F), Jodal-Bröchner-Mortensen (JBM), and Ng (N) (equations are given in Supplementary Table S1).3Brochner-Mortensen J. A simple method for the determination of glomerular filtration rate.Scand J Clin Lab Invest. 1972; 30: 271-274Crossref PubMed Scopus (785) Google Scholar, 4Chantler C. Barratt T.M. Estimation of glomerular filtration rate from plasma clearance of 51-chromium edetic acid.Arch Dis Child. 1972; 47: 613-617Crossref PubMed Scopus (221) Google Scholar, 5Fleming J.S. Zivanovic M.A. Blake G.M. et al.Guidelines for the measurement of glomerular filtration rate using plasma sampling.Nucl Med Commun. 2004; 25: 759-769Crossref PubMed Scopus (229) Google Scholar, 6Jodal L. Brochner-Mortensen J. Jodal L. et al.Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: analytically correct relationship between total and one-pool clearance.Scand J Clin Lab Invest. 2009; 69: 305-313Crossref PubMed Scopus (58) Google Scholar, 7Ng D.K. Schwartz G.J. Jacobson L.P. et al.Universal GFR determination based on two time points during plasma iohexol disappearance.Kidney Int. 2011; 80: 423-430Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Few data are available on the comparison between these models. This is the goal of the current study. From 6 different cohorts,8Bukabau J.B. Yayo E. Gnionsahé A. et al.Performance of creatinine- or cystatin C–based equations to estimate glomerular filtration rate in sub-Saharan African populations.Kidney Int. 2019; 95: 1181-1189Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar,9Delanaye P. Flamant M. Dubourg L. et al.Single- versus multiple-sample method to measure glomerular filtration rate.Nephrol Dial Transplant. 2018; 33: 1778-1785Crossref PubMed Scopus (12) Google Scholar we collected results of measured GFR by plasma clearance (iohexol or 51Cr−ethylenediamine tetraacetic acid [EDTA]) and compared the results obtained with the different correction equations (methods are described in detail in the Supplementary Methods). Among the 5459 participants, the mean age was 53 ± 17 years, and 42.9% were women. Mean height and body weight were 168 ± 10 cm and 73 ± 17 kg, respectively. Mean body mass index (BMI) and body surface area (BSA) were 26 kg/m2 ± 6 kg/m2 and 1.85 m2 ± 0.24 m2, respectively. Mean measured GFR (mGFR) with C, BM, F, JBM, and Ng was 63 ml/min per 1.73 m2 ± 28 ml/min per 1.73 m2, 64 ml/min per 1.73 m2 ± 25 ml/min per 1.73 m2, 63 ml/min per 1.73 m2 ± 24 ml/min per 1.73 m2, 64 ml/min per 1.73 m2 ± 25 ml/min per 1.73 m2, and 65 ml/min per 1.73 m2 ± 26 ml/min per 1.73 m2, respectively. Lin’s concordance correlation coefficient and biases are described in detail in Supplementary Table S2 in the Supplementary Material, but all comparisons showed almost perfect correlation (with concordance correlation coefficients >0.99). Regarding bias, all comparisons showed that bias was not relevant from a clinical perspective (the highest bias being 3 ml/min per 1.73 m2). All concordance within 10% and 5% are given in Table 1. Concordance within 10% is 100% for all comparisons, except when C equation is considered. Within 5% concordance was also close to 100% for all equations, except between F and N and when the C equation is considered in the comparison. Subanalyses (see Supplemental Material) were repeated in subgroups according to GFR levels in Supplementary Table S3 (based on the BM method in 6 categories: >130 ml/min per 1.73 m2, 90−130 ml/min per 1.73 m2, 60−90 ml/min per 1.73 m2, 45−60 ml/min per 1.73 m2, 30−45 ml/min per 1.73 m2, and ≤30 ml/min per 1.73 m2), sex in Supplementary Table S4, BMI in Supplementary Table S5 (<18.5 kg/m2, 18.5−25 kg/m2, 25−30 kg/m2, 30−35 kg/m2, 35−40 kg/m2, and ≥40 kg/m2, respectively), and age in Supplementary Table S6 (categorized in decades). Conclusions were not different from those of the total cohort when analyses were made according to sex or BMI. Only the variable GFR level influenced concordance, with less concordance in high GFR levels, even if results were still quite similar between BM and F, BM and JBM, and F and JBM. Excluding results from the C equation which is, once again, the most discrepant, we observed a discordance of more than 5% when the slow GFR was above 290, 290, 155, 290, 117, and 128 ml/min per 1.73 m2 comparing BM-F, BM-JBM, BM-N, F-JBM, F-N, and JBM-N, respectively.Table 1Concordance within 10% (above diagonal) and within 5% (below diagonal)CBMFJBMNC—97.196.896.291.7BM51.9—100100100F59.6100—100100JBM54.3100100—100N37.498.890.798.9—BM, Bröchner-Mortensen; C, Chantler; F, Fleming; JBM, Jodal-Bröchner-Mortensen; N, Ng.All results are expressed as percentages. Open table in a new tab BM, Bröchner-Mortensen; C, Chantler; F, Fleming; JBM, Jodal-Bröchner-Mortensen; N, Ng. All results are expressed as percentages. To the best of our knowledge, the current, multicentric study is the largest one comparing the different equations to correct the overestimation of the GFR obtained from the slow compartment. Two important conclusions should be drawn. First, the method proposed by Chantler in 1969 deviated most from all other methods. It can be reasonably presumed that this method was an oversimplification (C correction is just a linear correction), and we recommend that it should be abandoned. Second, all other models give very similar results, except at high GFR levels. The BM correction is the mostly used in the literature with iohexol and 51Cr-EDTA, whereas the F model is mostly used with 99Tc−diethylene triamine pentaacetic acid (DTPA), but obviously all these equations are interchangeable. More discrepancies can be observed at very high GFR levels. However, these discrepancies are observed at GFR levels which are higher than the threshold usually considered for the diagnosis of hyperfiltration, and therefore the clinical impact of such discrepancies is limited. BM correction is known to underestimate renal clearance at such high GFR levels. The performance of other equations at such high levels is not well known. The main limitation of the current analysis is the absence of renal/urinary clearance and/or plasma samples in the first (or early) compartment. Thus, we can assert that all equations, except the C one, are equivalent when measured GFR is lower than 130 ml/min 1.73 m2, but it remains difficult to know which one is the most accurate in the highest range of GFR. Further studies in this specific range of GFR are still required. All the authors declared no competing interests. We thank all the nurses and colleagues who helped in the GFR procedures or calculations: Arnaud Borsu and Jean Damascène Barahira in Liège, Markus van der Giet in Berlin, and the nurses from the “Clinique de médecine ambulatoire” unit in the Edouard Herriot Hospital in Lyon. Download .pdf (.34 MB) Help with pdf files Supplementary File (PDF) Comparison of Iohexol Plasma Clearances Calculated From 5 Early-Compartment Correction Equations With Urinary Clearance of IohexolKidney International ReportsVol. 5Issue 10PreviewWe read with great interest the publication of Delanaye et al.1 comparing 5 early-compartment correction equations for glomerular filtration rate (GFR) measurements. The authors concluded that most equations (Bröchner-Mortensen, Fleming, Jodal-Bröchner-Mortensen, and Ng) were concordant, except for Chantler’s equation that deviated from others; however, the lack of comparison with urinary clearance of exogenous tracers was underscored as a major limitation. Full-Text PDF Open AccessThe Authors ReplyKidney International ReportsVol. 5Issue 10PreviewResults proposed by Stehlé et al. regarding our article on the different methods to correct for the early-compartments for the determination of GFR by plasma clearances1 is of interest because data comparing plasma versus urinary clearances are relatively rare.2 In our article, we fairly stated that we had no urinary clearances, and thus our analysis was just a comparison of current equations to correct for the early-compartment.1 Stehlé et al. perfectly confirmed what we showed: a high concordance of the results given by the Bröchner-Mortensen, Fleming, Jodal-Bröchner-Mortensen, and Ng, whereas the Chantler correction gave different results. Full-Text PDF Open Access