Day-to-day variability in spot urine protein-creatinine ratio measurements

Abstract

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.