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

Am J Kidney Dis. 2010 Jul;56(1):39-49. doi: 10.1053/j.ajkd.2010.02.347.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Female
  • Glomerular Filtration Rate* / physiology
  • Humans
  • Iothalamic Acid*
  • Kidney Diseases / diagnosis*
  • Kidney Diseases / diagnostic imaging
  • Kidney Diseases / urine*
  • Kidney Function Tests / standards*
  • Male
  • Metabolic Clearance Rate* / physiology
  • Middle Aged
  • Radionuclide Imaging
  • Reference Standards
  • Statistics as Topic / methods
  • Statistics as Topic / standards


  • Iothalamic Acid