Day-to-day variability in spot urine albumin-creatinine ratio

Background: Accurate quantification of albuminuria is important in the diagnosis and management of chronic kidney disease. The reference test, a timed urinary albumin excretion, is cumbersome and prone to collection errors. Spot urine albumin-creatinine ratio (ACR) is convenient and commonly used, but random day-to-day variability in ACR measurements has not been assessed.

Study design: Prospective cohort study of day-to-day variability in spot urine ACR measurements.

Setting & participants: Clinically stable outpatients (N = 157) attending a university hospital clinic in Australia between July 2007 and April 2010.

Outcomes: Spot urine ACR variability was assessed and repeatability limits were determined using fractional polynomials.

Measurements: ACRs were measured from spot urine samples collected at 9:00 am on consecutive days and 24-hour urine albuminuria was measured concurrently.

Results: Paired ACRs were obtained from 157 patients (median age, 56 years; 60% men; median daily albumin excretion, 226 [range, 2.5-14,000] mg/d). Day-to-day variability was substantial and increased in absolute terms, but decreased in relative terms, with increasing baseline ACR. For patients with normoalbuminuria (ACR < 3 mg/mmol [<27 mg/g]), a change greater than ±467% (0-17 mg/mmol [0-150 mg/g]) is required to indicate a significant change in albuminuria status with 95% certainty; for those with microalbuminuria (ACR of 3-30 mg/mmol [27-265 mg/g]), a change of ±170% (0-27 mg/mmol [0-239 mg/g]) is required; for those with macroalbuminuria (ACR > 30 mg/mmol [>265 mg/g]), a change of ±83% (5-55 mg/mmol [44-486 mg/g]) is required; and for those with nephrotic-range proteinuria (ACR > 300 mg/mmol [>2,652 mg/g]), a change of ±48% (158-443 mg/mmol [1,397-3,916 mg/g]) is needed to represent a significant change.

Limitations: These study results need to be replicated in other ethnic groups.

Conclusions: Changes in chronic kidney disease status attributed to therapy or disease progression, when based solely on a change in ACR, may be incorrect unless the potential for day-to-day biological variation has been considered. Only relatively large changes are likely to indicate a change in disease status.