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. 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. Prospective cohort study of day-to-day variability in spot urine ACR measurements. Clinically stable outpatients (N = 157) attending a university hospital clinic in Australia between July 2007 and April 2010. Spot urine ACR variability was assessed and repeatability limits were determined using fractional polynomials. ACRs were measured from spot urine samples collected at 9:00 am on consecutive days and 24-hour urine albuminuria was measured concurrently. 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. These study results need to be replicated in other ethnic groups. 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.