What is the best method of proteinuria measurement in clinical trials of
endothelin receptor antagonists?
Author(s): Towler JD, Dhaun N, MacDougall M, Melville V, Goddard J, Webb DJ.
Affiliation(s): Clinical Pharmacology Unit, University of Edinburgh, The Queen's Medical Research
Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom.
D.J.Webb@ed.ac.uk
Publication date & source: 2012, Life Sci. , 91(13-14):733-8
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.
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