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Randomized Controlled Trial
. 2010 Jul;56(1):39-49.
doi: 10.1053/j.ajkd.2010.02.347.

Imprecision of urinary iothalamate clearance as a gold-standard measure of GFR decreases the diagnostic accuracy of kidney function estimating equations

Yuen-Ting Diana Kwong  1 , Lesley A Stevens, Elizabeth Selvin, Yaping Lucy Zhang, Tom Greene, Frederick Van Lente, Andrew S Levey, Josef Coresh
Affiliations
Randomized Controlled Trial

Imprecision of urinary iothalamate clearance as a gold-standard measure of GFR decreases the diagnostic accuracy of kidney function estimating equations

Yuen-Ting Diana Kwong et al. Am J Kidney Dis. 2010 Jul.

Abstract

Background: Evaluating the accuracy of estimated glomerular filtration rate (eGFR) derived from serum creatinine (SCr) and serum cystatin C (SCysC) equations requires gold-standard measures of GFR. However, the influence of imprecise measured GFRs (mGFRs) on estimates of equation error is unknown.

Study design: Diagnostic test study.

Setting & participants: 1,995 participants from the Modification of Diet in Renal Disease (MDRD) Study and African American Study of Kidney Disease and Hypertension (AASK) with at least 2 baseline mGFRs from iodine 125-iothalamate urinary clearances, 1 standardized SCr value, and 1 SCysC value.

Index tests: eGFRs calculated using the 4-variable isotope-dilution mass spectrometry (IDMS)-traceable MDRD Study equation, the Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) SCysC equation, the CKD-EPI SCr-SCysC equation, and mGFRs collected from another prerandomization visit.

Reference tests: A single reference mGFR, average of 2, and average of 3 mGFRs; additional analysis limited to consistent mGFRs (difference <or=25% from reference mGFR).

Results: We found that mGFRs had stable mean values, but substantial variability across visits. Of all mGFRs collected a mean of 62 days apart from the reference visit, 8.0% were outside 30% of the single reference mGFR (1 - P(30)). Estimation equations were less accurate because 12.1%, 17.1%, and 8.3% of eGFRs from the MDRD Study, CKD-EPI SCysC, and CKD-EPI SCr-SCysC equations were outside 30% of the same gold standard (1 - P(30)). However, improving the precision of the reference test from a single mGFR to the average of 3 consistent mGFRs decreased these error estimates (1 - P(30)) to 8.0%, 12.5%, and 3.9%, respectively.

Limitations: Study population limited to those with CKD.

Conclusions: Imprecision in gold-standard measures of GFR contribute to an appreciable proportion of the cases in which eGFR and mGFR differ by >30%. Reducing and quantifying errors in gold-standard measurements of GFR is critical to fully estimating the accuracy of GFR estimates.

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Figures

Figure 1
Figure 1
Timeline of glomerular filtration rate (GFR) measurements in the African American Study of Kidney Disease (AASK) and Modification of Diet in Renal Disease (MDRD) Study. Symbols indicate mean period of randomization (rectangle), the collection of reference pre-randomization mGFR visit (diamond) when serum creatinine and serum cystatin C were also measured, the collection of another pre-randomization GFR (circle) and the collection of the first post-randomization mGFR (triangle).
Figure 2
Figure 2
Flowchart with exclusion and inclusion criteria. Abbreviations: measured glomerular filtration rates (mGFRs), serum creatinine (Scr), serum cystatin C (SCysC), Modification of Diet in Renal Disease (MDRD), and African American Study of Kidney Disease (AASK)
Figure 3
Figure 3
Bland-Altman plot of the difference of the two prerandomization glomerular filtration rate measurements (mGFRs) by the average of pre-randomization mGFRs.
Figure 4
Figure 4
Estimated accuracy of CKD-EPI SCr-SCysC equation and the Modification of Diet in Renal Disease (MDRD) Study equation in estimating six different gold standard measured glomerular filtration rates (mGFRs): reference mGFR, average of two mGFRs, and the average of three mGFRs without and with limiting the analysis to consistent (within 25% of each other) mGFRs. P30 is calculated as the percentage of estimated GFR within 30% of the gold standard (the average of three mGFRs).
See this image and copyright information in PMC

Comment in

  • Measured GFR has limited clinical utility.
    Nori US, Pesavento TE, Hebert LA. Nori US, et al. Am J Kidney Dis. 2011 Jan;57(1):180; discussion 180-1. doi: 10.1053/j.ajkd.2010.08.035. Am J Kidney Dis. 2011. PMID: 21184927 No abstract available.

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