Day-to-Day Variability in Spot Urine Protein-Creatinine Ratio Measurements

Background| Accurate measurement of proteinuria is important in the diagnosis and management of chronic kidney disease (CKD). The reference standard test, 24-hour urinary protein excretion, is inconvenient and vulnerable to collection errors. Spot urine protein-creatinine ratio (PCR) is a convenient alternative and is in widespread use. However, day-to-day variability in PCR measurements has not been evaluated. Study Design: Prospective cohort study of day-to-day variability in spot urine PCR measurement. Setting & Participants: Clinically stable outpatients with CKD (n = 145) attending a university hospital CKD clinic in Australia between July 2007 and April 2010. Index Test: Spot urine PCR. Outcomes: Spot PCR variability was assessed and repeatability limits were determined using fractional polynomials. Measurements: Spot PCRs were measured from urine samples collected at 9: 00 AM on consecutive days and 24-hour urinary protein excretion was collected concurrently. Results: Paired results were analyzed from 145 patients: median age, 56 years; 59% men; and median 24-hour urinary protein excretion, 0.7 (range, 0.06-35.7) g/d. Day-to-day variability was substantial and increased in absolute terms, but decreased in relative terms with increasing baseline PCR. For patients with a low baseline PCR (20 mg/mmol [177 mg/g]), a change greater than +/-160% (repeatability limits, 0-52 mg/mmol [0-460 mg/g]) is required to indicate a real change in proteinuria status with 95% certainty, whereas for those with a high baseline PCR (200 mg/mmol [1,768 mg/g]), a change of +/-50% (decrease to <100 mg/mmol [<884 mg/g] or increase to >300 mg/mmol [>2,652 mg/g]) represents significant change. Limitations: These study results need to be replicated in other ethnic groups. Conclusions: Changes in PCR observed in patients with CKD, ranging from complete resolution to doubling of PCR values, could be due to inherent biological variation and may not indicate a change in disease status. This should be borne in mind when using PCR in the diagnosis and management of CKD. Am J Kidney Dis. 60(4):561-566. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.