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

Life Sci. 2012 Oct 15;91(13-14):733-8. doi: 10.1016/j.lfs.2012.02.019. Epub 2012 Mar 3.

Abstract

Aims: To determine whether protein-creatinine ratio (PCR) and albumin-creatinine ratio (ACR) are comparable to 24h 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 24h urine protein (25 vs. 28%) but the range was higher (70 vs. 47%). When converted into the same units, mean difference between 24h 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.

Significance: PCR and ACR may well be suitable replacements for 24h 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 24h urine protein can be replaced.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / urine
  • Analysis of Variance
  • Creatinine / urine
  • Double-Blind Method
  • Drug Monitoring / methods
  • Endothelin Receptor Antagonists*
  • Humans
  • Isoxazoles / pharmacology*
  • Proteinuria / diagnosis*
  • Proteinuria / etiology
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / physiopathology*
  • Reproducibility of Results
  • Thiophenes / pharmacology*

Substances

  • Endothelin Receptor Antagonists
  • Isoxazoles
  • Thiophenes
  • Creatinine
  • sitaxsentan