What is the best method of proteinuria measurement in clinical trials of endothelin receptor antagonists?

Jonathan D. Towler, Neeraj Dhaun, Margaret MacDougall, Vanessa Melville, Jane Goddard, David J. Webb

Research output: Contribution to journalArticlepeer-review



To determine whether protein–creatinine ratio (PCR) and albumin–creatinine ratio (ACR) are comparable to 24 h urine protein in terms of agreement and repeatability, and therefore whether they are suitable for monitoring and comparing reduction in proteinuria in clinical trials of endothelin receptor antagonists.

Main methods

Using data from a recent study of sitaxentan in 27 patients with proteinuric chronic kidney disease, the assays were compared with reference to their agreement, repeatability, the number of measurements required to obtain accurate results and correlation with reduction in proteinuria at baseline.

Key findings

The median coefficient of variation was lower for PCR than 24 h urine protein (25 vs. 28%) but the range was higher (70 vs. 47%). When converted into the same units, mean difference between 24 h urine protein and both PCR (0.03 g/day), and ACR (0.10 g/day), was small. However, scatter increased with mean level of proteinuria, such that agreement fell substantially above 1.5 g/day. According to 2-factor within-subjects ANOVA, the assay used was not a significant source of variation (PCR p = 0.63, ACR p = 0.38). With 3 measurements at each time point, baseline proteinuria correlated equally well with change in proteinuria, and percentage change was detected accurately by all 3 methods.


PCR and ACR may well be suitable replacements for 24 h urine protein in the clinical trial context due to their similar accuracy and repeatability, greater convenience and lower cost. However, a randomised control trial comparing all 3 assays in a larger and more diverse population is necessary before 24 h urine protein can be replaced.
Original languageEnglish
Pages (from-to)733-738
JournalLife Sciences
Issue number13-14
Publication statusPublished - 15 Oct 2012


  • Protein–creatinine ratio
  • Albumin–creatinine ratio
  • Endothelin receptor antagonists
  • Sitaxentan
  • Chronic kidney disease
  • Hypertension


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